ObjectiveTo investigate the regulatory effect of icariin （ICA） on transforming growth factor-β₁ （TGF-β₁）/Smad pathway in bone microvascular endothelial cells （BMECs） and the effect on autophagy in BMECs. MethodsBMECs were isolated and cultured， and the cell types were identified by immunofluorescence. Cells were divided into the control group， model group （0.1 g·L^-1 methyl prednisolone）， ICA group （0.1 g·L^-1 methyl prednisolone +1×10^-5 mol·L^-1 ICA）， and TGF-β inhibitor group （0.1 g·L^-1 methyl prednisolone +1×10^-5 mol·L^-1 ICA +1×10^-5 mol·L^-1 LY2157299）. Transmission electron microscopy was used to observe the ultrastructure and autophagosome number of BMECs. Autophagy double-standard adenovirus was used to monitor the confocal autophagy flow generation of each cell. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the gene and protein expression of autophagy in the TGF-β₁/ Smad pathway. ResultsAfter cell separation culture， platelet endothelial cell adhesion molecule （CD31） and von willebrand factor （vWF） immunofluorescence identified BMECs. Transmission electron microscopy showed that the cell membrane was damaged， and the nucleus was pyknotic and broken in the model group. Compared with the model group， the ICA group had complete cell membranes， clear structures， with autophagy-lysosome sparsely distributed. The confocal photo showed that BMECs had autophagosomes and autophagy-lysosomes， and the autophagy expression of the ICA group was similar to that of the blank group. Compared with the blank group， in the model group and the LY2157299 group， autophagosomes and autophagy-lysosomes were barely seen in the autophagy flow. Compared with the blank group， the mRNA and protein expressions of autophagy effector protein 1 （Beclin1） and microtubule-associated protein 1 light chain 3B （LC3B） in the model group were significantly decreased （P<0.01）， and those of ubiquitin-binding protein （p62） were significantly increased （P<0.01）. The mRNA expression of TGF-β₁， Smad homolog 2 （Smad2）， and Smad homolog 3 （Smad3） decreased （P<0.05， P<0.01）. The protein expressions of TGF-β₁， p-Smad2， and p-Smad3 were significantly decreased （P<0.01）. Compared with those of the model group， the mRNA and protein expression of Beclin1 and LC3B in BMECs of the ICA group increased （P<0.01）， and those of p62 significantly reduced （P<0.01）. The mRNA expression of TGF-β₁， Smad2， and Smad3 increased significantly （P<0.01）. The protein expression of TGF-β₁， p-Smad2， and p-Smad3 increased significantly （P<0.01）. Compared with those in the model group， the mRNA and protein expressions of Beclin1， LC3B， and p62 in the inhibitor group were not statistically significant. The expression of key genes and proteins of the TGF-β₁ pathway in the inhibitor group was not statistically significant. ConclusionICA can promote glucocorticoid-induced autophagy expression of BMECs， and its mechanism may be related to activating the TGF-β₁/Smad signaling pathway.

Steroid-induced osteonecrosis of the femoral head （SONFH） is a severe musculoskeletal disorder often induced by the prolonged or excessive use of glucocorticoids. Characterized by ischemia of bone cells， necrosis， and trabecular fractures， SONFH is accompanied by pain， femoral head collapse， and joint dysfunction， which can lead to disability in severe cases. The pathogenesis of SONFH involves hormone-induced osteoblast apoptosis， bone microvascular endothelial cell （BMEC） apoptosis， oxidative stress， and inflammatory responses. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a pivotal role in the development of the disease. Modulating the PI3K/Akt signaling pathway can promote Akt phosphorylation， thereby stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts， promoting angiogenesis in BMECs， and inhibiting osteoclastogenesis. The research on the treatment of SONFH with traditional Chinese medicine （TCM） has gained increasing attention. Recent studies have shown that TCM monomers and compounds have potential therapeutic effect on SONFH by intervening in the PI3K/Akt signaling pathway. These studies not only provide a scientific basis for the application of TCM in the treatment of SONFH but also offer new ideas for the development of new therapeutic strategies. This review summarized the progress in Chinese and international research on the PI3K/Akt signaling pathway in SONFH over the past five years. It involved the composition and transmission mechanisms of the signaling pathway， as well as its regulatory effects on osteoblasts， mesenchymal stem cells， osteoclasts， BMECs， and other cells. Additionally， the review explored the TCM understanding of SONFH and the application of TCM monomers and compounds in the intervention of the PI3K/Akt pathway. By systematically analyzing and organizing these research findings， this article aimed to provide references and point out directions for the clinical prevention and treatment of SONFH and promote further development of TCM in this field. With in-depth research on the PI3K/Akt pathway and the modern application of TCM， it is expected to bring safer and more effective treatment options for patients with SONFH.

AIM: To explore the correlation between neonatal retinal hemorrhage(RH)and changes in umbilical artery blood gas analysis.METHODS: A total of 312 full-term neonates born in our obstetrics department from January 2019 to December 2021 were selected as the study subjects. According to the RetCam III fundus examination results, 245 neonates who did not experience RH were included in the control group, while 67 cases with RH were found to be included in the RH group. In addition, neonates were grouped into I degree group(n=20), II degree group(n=29), and III degree group(n=18)based on the degree of RH. General clinical data and umbilical artery blood gas analysis indicators between the RH group and the control group were compared; the levels of umbilical artery blood gas analysis indicators in neonates with different degrees of RH, the relationship between pH and RH degree, and the influencing factors of neonatal RH were analyzed.RESULTS: There was no obvious difference in maternal age, average gestational week, fetal gender, parity, gestational diabetes, fetal birth weight, and amniotic fluid between the RH group and the control group(all P>0.05), while there were obvious differences in delivery methods, gestational hypertension, forceps assisted delivery, neonatal asphyxia, and umbilical cord around the neck(all P<0.05). The pH value, arterial blood sample partial pressure(PaO2)and base excess(BE)values of the RH group were obviously lower than those of the control group(all P<0.01), while the arterial carbon dioxide partial pressure(PaCO2)was obviously higher than that of the control group(P<0.01). There were obvious differences in umbilical artery blood gas analysis indicators among children with different degrees of RH(P<0.05), and with the increase of the degree of RH, pH value, PaO2 and BE gradually decreased(P<0.05), and PaCO2 gradually increased(P<0.05). There was a negative correlation between the degree of RH and the pH of umbilical artery blood gas analysis(rs=-0.593, P<0.05). The results of multivariate Logistic regression analysis showed that delivery method, gestational hypertension, forceps assisted delivery, neonatal asphyxia, umbilical cord entanglement, pH, PaO2, PaCO2, and BE were all influencing factors for the occurrence of neonatal RH.CONCLUSION: There is a close correlation between neonatal RH and changes in umbilical artery blood gas analysis, and umbilical artery blood gas analysis can be used for the diagnosis of neonatal RH, which can be used to guide clinical treatment.

Flubromazolam(Flub)is a novel psychoactive substance of benzodiazepines and the mechanism underlying its addiction still remains elusive.This study investigated the reward effect of Flub using conditioned place preference(CPP)mouse model.The neuronal activity was evaluated by c-Fos expression,and the neural circuit was tracked by virus tracing.This study also investigated the regulatory effect of neural circuits on Flub-induced reward effects through chemogenetic approach.The results showed that,at the dose of 3 mg/kg,Flub significantly increased CPP score and c-Fos expression in dopaminergic(DA)neurons of ventral tegmental area(VTA).Inhibition of VTA dopaminergic neuron activity dramatically decreased Flub-induced CPP score.Virus tracing verified GABAergic neuronal projection of medial rostrum tegmental nucleus(RMTg)to VTA dopaminergic neurons.Activation of RMTgGABA→VTADA circuit or blockade of benzodiazepine receptors(BZR)in RMTg significantly decreased Flub-induced CPP score.These results indicate that Flub produced reward effect via BZR-mediated RMTgGABA→VTADA circuit.

Objective:To explore the clinical efficacy of endoscopic sleeve gastrectomy (ESG) in the treatment of obesity.Method:A 26 year old female patient was admitted on October 20, 2022 due to a progressive increase in weight for 2 years. Her body mass index (BMI) was 30.04 kg/m 2, body fat percentage was 39.2%, and visceral fat grade was 15. ESG was performed using the OverStitch SX endoscopic suture system. Result:The surgery was successful, with approximately 5 ml of intraoperative bleeding.The patient discharged on the first day after surgery. Two weeks after surgery, small bowel follow-through showed a tubular shape of the stomach. At 6 months after surgery, the BMI was 25.2 kg/m 2, body fat percentage was 32%, visceral fat grade was 10. The total body weight loss rate (%TBWL) at 6 months after surgery was 16%, and the excess weight loss rate (%EWL) was 54.5%. Conclusion:ESG is effective for the treatment of obesity.

Background::Thoracic aortic aneurysm (TAA) is a fatal cardiovascular disease, the pathogenesis of which has not yet been clarified. This study aimed to identify and validate the diagnostic markers of TAA to provide a strong theoretical basis for developing new methods to prevent and treat this disease.Methods::Gene expression profiles of the GSE9106, GSE26155, and GSE155468 datasets were acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the "limma" package in R. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), random forest, and binary logistic regression analyses were used to screen the diagnostic marker genes. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate immune cell infiltration in TAA.Results::A total of 16 DEGs were identified. The enrichment and functional correlation analyses showed that DEGs were mainly associated with inflammatory response pathways and collagen-related diseases. Collagen type I alpha 1 chain ( COL1A1) and synaptotagmin like 2 ( SYTL2) were identified as diagnostic marker genes with a high diagnostic value for TAA. The expression of COL1A1 and SYTL2 was considerably higher in TAA vascular wall tissues than in the corresponding normal tissues, and there were significant differences in the infiltration of immune cells between TAA and normal vascular wall tissues. Additionally, COL1A1 and SYTL2 expression were associated with the infiltration of immune cells in the vascular wall tissue. Single-cell analysis showed that COL1A1 in TAA was mainly derived from fibroblasts and SYTL2 mainly from cluster of differentiation (CD)8 + T cells. In addition, single-cell analysis indicated that fibroblasts and CD8 + T cells in TAA were significantly higher than those in normal arterial wall tissue. Conclusions::COL1A1 and SYTL2 may serve as diagnostic marker genes for TAA. The upregulation of SYTL2 and COL1A1 may be involved in the inflammatory infiltration of the vessel wall and poor extracellular matrix remodeling, promoting the progression of TAA.

At present, the incidence and mortality of tumors are increasing, and the treatment of tumors has attracted much attention. Radiotherapy is a key method for tumor treatment; however, its effectiveness is often constrained by radioresistance. During tumor radiotherapy, DNA damage response (DDR) is a key factor in the radioresistance of tumor cells. Research has shown that the radiosensitivity of tumor cells can be effectively improved by regulating the expression of key proteins in the DDR pathway. Targeting the DDR signaling pathway has become an effective strategy to reduce tumor radioresistance. This article focuses on the mechanisms, clinical research status, limitations, and current challenges associated with the key DDR proteins DNA-PKcs, ATM, ATR, and PARP as therapeutic targets for tumor radiotherapy sensitization, in order to provide a reference for the development of radiotherapy sensitization agents.

Objective:To explore the clinical efficacy of endoscopic sleeve gastrectomy (ESG) in the treatment of obesity.Method:A 26 year old female patient was admitted on October 20, 2022 due to a progressive increase in weight for 2 years. Her body mass index (BMI) was 30.04 kg/m 2, body fat percentage was 39.2%, and visceral fat grade was 15. ESG was performed using the OverStitch SX endoscopic suture system. Result:The surgery was successful, with approximately 5 ml of intraoperative bleeding.The patient discharged on the first day after surgery. Two weeks after surgery, small bowel follow-through showed a tubular shape of the stomach. At 6 months after surgery, the BMI was 25.2 kg/m 2, body fat percentage was 32%, visceral fat grade was 10. The total body weight loss rate (%TBWL) at 6 months after surgery was 16%, and the excess weight loss rate (%EWL) was 54.5%. Conclusion:ESG is effective for the treatment of obesity.

Objective To observe the effects of electroacupuncture on the motor function and expressions of Irisin,Decorin and Myostatin in skeletal muscle of SAMP8 mice;To explore the mechanism of electroacupuncture in the treatment of the motor dysfunction of Alzheimer disease(AD).Methods Totally 247-month-old male SAMP8 mice were randomly divided into model group and electroacupuncture group,with 12 mice in each group,and the 12 male SAMR1 mice with the same age were set as the control group."Baihui","Dazhui"and"Shenshu"were selected in the electroacupuncture group,once a day,8 days as one course of treatment,with an interval of 2 days,for a total of 3 courses.The control group and the model group were not intervened.The motor function of mice was tested by grip strength test,pole climbing test and open field test,the mRNA expressions of Irisin,Decorin and Myostatin in quadriceps muscle were detected by RT-qPCR,and the protein expressions of Irisin,Decorin and Myostatin in quadriceps muscle were detected by immunohistochemistry and Western blot.Results Compared with the control group,the grip peak and duration of the mice in the model group decreased,head turning time and pole climbing time were prolonged(P<0.01),the mRNA and protein expressions of Irisin and Decorin decreased(P<0.05,P<0.01),and the expressions of Myostatin mRNA and protein increased(P<0.05).Compared with the model group,the grip peak and duration of the mice in the electroacupuncture group increased,head turning time and pole climbing time were decreased(P<0.05),the mRNA and protein expressions of Irisin and Decorin increased(P<0.05),and the expressions of Myostatin mRNA and protein decreased(P<0.05).Conclusion Electroacupuncture can improve the motor dysfunction of SAMP8 mice,and its mechanism may be related to regulating the expressions of Irisin,Decorin and Myostatin in skeletal muscle.

Objective:To analyze the safety and efficacy of ultrasound-guided needle-perc assisted retrograde intrarenal surgery (RIRS) in the treatment of small but complex renal calculi, and summarize our clinical experience.Methods:The clinical data of 36 patients with small but complicated renal stones treated by ultrasound-guided needle-perc assisted RIRS in Beijing Tsinghua Changgung Hospital from January 2020 to April 2022, were retrospectively analyzed. There were 25 males and 11 females. The average age was (54.7±6.1) years, and the body mass index (BMI) was (26.3±3.1) kg/m 2. The maximum diameter of the calculi was (1.8±0.7) cm. There were 28 patients without renal hydronephrosis before operation, 8 patients with mild to moderate renal hydronephrosis, 4 patients with caliceal diverticular stones, 32 patients with lower pole stones, 10 patients with ureteral stones, 6 patients with previous surgical history of ipsilateral kidney stones, and 3 patients with stones in the solitary kidneys. Patients were placed in oblique supine lithotomy position or prone split leg position (female). For lower pole stones or diverticular stones that were difficult to be handled by flexible ureteroscope, the needle-perc was used to puncture the stones in target calyx under ultrasound guidance. Holmium laser was then used to pulverize or fragment the calculi, and the flexible ureteroscope was used to remove or further pulverize the stone fragments. Perioperative indexes and postoperative complications were recorded, and stone-free rate was analyzed. Results:All 36 cases were successfully operated. The median operation time was 61.5(59.0, 66.8)min, with a median decrease in hemoglobin on the first postoperative day of 1.6(0.8, 2.0)g/ L, a median postoperative hospital stay of 1.5(1.0, 2.0)days, and a median needle-perc tract of 1(1, 2). The complications were recorded in 4 patients (11.1%), all of which were Clavien-Dindo grade I, including postoperative fever in 2 patients and analgesic use in 2 patients. The primary stone-free rate was 83.3% (30/36). The 6 patients with residual stones were treated by external physical vibration lithecbole on the 3rd to 7th day after surgery. After 1 month follow-up, residual stone expulsion were seen in 3 patients. Three patients with residual stones were followed up regularly. The final stone-free rate was 91.7% (33/36).Conclusions:Ultrasound-guided needle-per assisted RIRS is safe and effective in the treatment of small but complex renal calculi, with high postoperative stone free rate and low complication rate.