Stent migration is one of the common complications following transcatheter valve implantation. This study aims to design a "drum-shaped" balloon-expandable aortic valve stent to address this issue and conduct a mechanical analysis. The implantation process of the stent was evaluated using a method that combines numerical simulation and in vitro experiments. Furthermore, the fatigue process of the stent under pulsatile cyclic loading was simulated, and its fatigue performance was assessed using a Goodman diagram. The process of the stent migrating toward the left ventricular side was simulated, and the force-displacement curve of the stent was extracted to evaluate its anti- migration performance. The results showed that all five stent models could be crimped into a 14F sheath and enabled uniform expansion of the native valve leaflets. The stress in each stent was below the ultimate stress, so no fatigue fracture occurred. As the cell height ratio decreased, the contact area fraction between the stent and the aortic root gradually decreased. However, the mean contact force and the maximum anti-migration force first decreased and then increased. Specifically, model S5 had the smallest contact area fraction but the largest mean contact force and maximum anti-migration force, reaching approximately 0.16 MPa and 10.73 N, respectively. The designed stent achieves a "drum-shaped" change after expansion and has good anti-migration performance.
Stents ; Prosthesis Design ; Heart Valve Prosthesis ; Humans ; Aortic Valve/surgery* ; Stress, Mechanical ; Transcatheter Aortic Valve Replacement/instrumentation*

The tumor microenvironment includes blood vessels， lymph， nerves， non-malignant cells， and their metabolites at and near the tumor lesion site， which interact with cancer cells and promote cancer progression. Rapid proliferation of cancer cells increases oxygen consumption， or abnormalities in the structure and function of blood vessels in solid tumors lead to a decrease in oxygen supply， forming a hypoxia microenvironment. The existence of a hypoxia microenvironment is a typical pathophysiological feature of locally advanced solid tumors， widely present in various types of human malignant tumors. Hypoxia microenvironment is a sign of tumor microenvironment and an important and complex system in the breast tumor microenvironment. Its formation and development are closely related to the growth of breast cancer， occupying an important position in the research and treatment of breast cancer. With its advantages of multiple pathways and multiple targets， the effective monomer and compound of traditional Chinese medicine can better regulate the hypoxia microenvironment of breast cancer， inhibit the proliferation， invasion， and metastasis of breast cancer cells in the hypoxia environment， induce apoptosis， reverse their drug resistance， intervene in the metabolic reprogramming of breast cancer cells in the hypoxia environment， and inhibit their angiogenesis， thereby improving the quality of life of patients to a certain extent and prolonging the survival cycle of patients. This paper first summarized and discussed the effects of hypoxia microenvironment on proliferation， invasion， metastasis， drug resistance， immune function， metabolic reprogramming， non-coding RNA， iron death， and autophagy of breast cancer cells， which affected the occurrence and development of breast cancer， and it elaborated the mechanism behind it. Then， the paper elucidated the regulatory effect and mechanism of targeting the hypoxia microenvironment based on the two modes of effective monomer and compound of traditional Chinese medicine， so as to analyze and extract the deficiencies and directions of traditional Chinese medicine in regulating the hypoxia microenvironment and provide a theoretical reference for the effective treatment of breast cancer.

Ossification of the posterior longitudinal ligament (OPLL) is a condition comprising ectopic bone formation from spinal ligaments. This disease is a leading cause of myelopathy in the Asian population. However, the molecular mechanism underlying OPLL and efficient preventive interventions remain unclear. Here, we performed single-cell RNA sequencing and revealed that type I interferon (IFN) signaling was activated in the ossified ligament of patients with OPLL. We also observed that IFN-β stimulation promoted the osteogenic differentiation of preosteoblasts in vitro and activated the ossification-related gene SPP1, thereby confirming the single-cell RNA sequencing findings. Further, blocking the IFN-α/β subunit 1 receptor (IFNAR1) using an anti-IFNAR1 neutralizing antibody markedly suppressed osteogenic differentiation. Together, these results demonstrated that the type I IFN signaling pathway facilitated ligament ossification, and the blockade of this signaling might provide a foundation for the prevention of OPLL.
Humans ; Signal Transduction ; Interferon Type I/metabolism* ; Ossification of Posterior Longitudinal Ligament/genetics* ; Gene Expression Profiling ; Single-Cell Analysis ; Osteogenesis/genetics* ; Receptor, Interferon alpha-beta/metabolism* ; Male ; Female ; Cell Differentiation ; Middle Aged

ObjectiveTo investigate the effects of spleen-Yin deficiency on gastrointestinal absorption， water metabolism and intestinal flora in rats with spleen-Yin deficiency syndrome. MethodA rat model of spleen-Yin deficiency syndrome was established by using the composite factors， including irregular meat and vegetable diet， weight-bearing fatigue swimming and gavage with warm-heat injury-Yin drugs. The changes of body weight， food intake， water intake and duration of swimming in the blank and model groups were observed. Hematoxylin-eosin（HE） staining was used to observe the histopathological damage of the stomach and colon. Urinary excretion rate of D-xylose was determined by phloroglucinol method. The content of gastrin（GAS） in serum was determined by enzyme-linked immunosorbent assay（ELISA）. The relative expression levels of vasoactive intestinal peptide（VIP）， aquaporin 3（AQP3） and AQP4 in gastric tissues were detected by Western blot. The relative mRNA expression levels of VIP， AQP3 and AQP4 in gastric tissues were detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the changes of intestinal flora were analyzed by 16S rDNA sequencing. ResultCompared with the blank group， the results of general physical signs showed that the body weight and food intake of rats in the model group were significantly decreased， the water intake was significantly increased（P<0.05， P<0.01）， and the duration of swimming was significantly decreased（P<0.01）. Pathological examination results showed that in the mucosa of gastric tissues of rats in the model group appeared to be misaligned， the mucosa of colonic tissues could be seen to be obviously thinned or mutilated， and the epithelial cells appeared to be necrotic or even exfoliated. Compared with the blank group， the urinary D-xylose excretion rate of rats in the model group was significantly decreased（P<0.01）， and the serum GAS content was significantly decreased（P<0.05）. Compared with the blank group， Western blot results showed that the relative expression level of VIP protein in gastric tissues of rats in the model group was significantly decreased， while the relative expression levels of AQP4 and AQP3 proteins were significantly increased（P<0.01）. Compared with the blank group， Real-time PCR results showed that the relative expression level of VIP mRNA in gastric tissues of rats in the model group was significantly decreased（P<0.01）， and the relative mRNA expression levels of AQP3 and AQP4 were significantly increased（P<0.05， P<0.01）. Compared with the blank group， the results of intestinal flora analysis showed that the number of operational taxonomic units（OTUs） and α-diversity increased and β-diversity decreased significantly in the model group， the abundance of Porphyromonadaceae was increased significantly， and the abundance of Oscillibacter_ruminantium was decreased significantly（P<0.05）. Spearman correlation analysis showed that Porphyromonadaceae was significantly positively correlated with AQP4 protein level， while Oscillibacter_ruminantium was significantly positively correlated with VIP protein level， and negatively correlated with AQP3 and AQP4 protein levels（P<0.05）. Linear discriminant analysis effect size（LEfSe） analysis results showed that there were significant differences in a variety of intestinal bacteria between groups， and the intestinal bacteria of the model group were significantly enriched in the phylum/order/family/genus of Elusimicrobia， Betaproteobacteria， Burkholderiales， Sutterellaceae and Parasutterella（P<0.05）. ConclusionSpleen-Yin deficiency syndrome can weaken the digestion and absorption capacity of gastrointestinal tract， and cause the disturbance of water metabolism and intestinal flora. AQP4， AQP3 and VIP protein levels of gastric mucosa are closely related to Porphyromonadaceae and Oscillibacter_ruminantium. And AQP4， AQP3 and VIP may be involved in the regulation of intestinal flora in order to affect the physiological function of spleen governing transportation and transformation.

Vagus nerve reflex is a rare complication of percutaneous renal decompression. It is often induced by excessively rapid decompression of severe hydronephrosis and traction of the main nerves innervating the kidney. The clinical manifestations are irritability, sweating, clammy skin, hiccups, slow heart rate. It is easy to misdiagnose. In this study, 4 patients with vagus nerve excitement after percutaneous renal decompression were treated. After monitoring the patient’s vital signs and giving treatment such as expanding blood volume and raising blood pressure, the symptoms gradually disappeared.

Objective: To explore the feasibility of the modified RUSS (Resorlu-Unsal Stone Score) renal stone scoring system in predicting the stone free rate after Flexible Ureteroscopic Lithotripsy(FURL). Methods: Retrospective analysis was performed on 104 cases of renal stones treated by FURL from March 2017 to January 2019 in the second affiliated hospital of zhengzhou university, including 75 males and 29 females. Age 20-75 (47.79±13.21) years. BMI 18.2-38.3 (24.4±3.7) kg/m²; Crushed stone site: left 56 cases, right 48 cases. There were 23 cases of renal inferior calyces calculi, 81 cases of non-inferior calyces calculi, and 19 cases of renal inferior calyces calculi with IPA<45°; American Society of Anesthesiology (ASA) scores: 65 cases of grade Ⅰ, 39 cases of grade Ⅱ; There were 71 patients with urinary tract infection before operation. There were 6 cases of renal puncture fistula before operation. Preoperative indwelling ureteral stent in 26 cases; There were 32 cases with history of extracorporeal shock wave lithotripsy. There were 27 patients with a history of urolithiasis therapy. The same physician used preoperative urinary CT+ 3D reconstruction imaging data to measure the factors influencing the postoperative stone free rate. RUSS renal stone scoring system was used to score the stones of patients before operation, and the relationship between the scores and the stones free rate was analyzed. The RUSS renal stone scoring system was supplemented and improved by including staghorn stone, duplicate renal, caliceal diverticulum, renal malrotation, stone area, and CT value related indexes. The modified RUSS renal stone scoring system was used to score the preoperative stone condition of patients, and the relationship between the score and the stone free rate was analyzed. The receiver operating characteristic curve (ROC) was drawn and the area under the curve (AUC) was calculated to compare the advantages and disadvantages of the modified RUSS, the characteristics of the stones, and RUSS system. Results: The stone free rate was 69.2% (72/104) 4 weeks after the operation, and there were no postoperative complications. Single-factor analysis showed that stone area, CT value, number of renal calyx involved by stone, multiple stones, IPA, stone size grading, renal anatomic structure abnormality, staghorn stone were all related risk factors affecting postoperative patients. Multi-factor analysis showed that stone area, number of renal calyces involved by stone, multiple stones, IPA and stone size were independent risk factors affecting the stone free rate after FURL. RUSS scores ranged from 0 to 3 points, corresponding to stone clearing rates of 86.8% (33/38), 67.7% (23/34), 58.3% (14/24) and 25.0% (2/8), respectively. Stone clearing rates were significantly correlated with stone grading (P<0.05). The total scores of stone free group and residual stone group were (0.87±0.96) points and (1.53±0.98) points, respectively, with significant differences between the groups (P<0.05). The range of modified RUSS score was 0-4 points, corresponding to the stone clearing rate of 100.0% (25/25), 92.3% (24/26), 54.2% (13/24), 47.4% (9/19), and 10.0% (1/10), respectively. Stone free rate was significantly correlated with stone grading (P<0.05). The total scores of stone free group and residual stone group were (1.15±1.13) points and (2.81±0.93) points, respectively, with significant differences between the groups (P<0.05). The AUC of stone features was smaller than that of the modified RUSS scoring system. The AUC of RUSS scoring system (0.707, 95%CI 0.598-0.815) was smaller than that of the modified RUSS scoring system (0.865, 95%CI 0.797-0.933). Conclusions Both the RUSS scoring system and the modified RUSS scoring system could accurately predict the postoperative stone free status of FURL, while the modified RUSS scoring was more accurate than the RUSS scoring.

Objective To systematically evaluate the optimal indwelling time of double?J stent in the treatment of ureteral complicated calculi post?ureteroscopy. Methods A total of 161 patients with complicated ureteral calculi were enrolled in this study from August 2012 to August 2015. All patients received the treatment of ureteroscopic holmium YAG Laser lithotripsy and were randomly divided into 3 groups according to varied double?J stent indwelling time: group A < 2 weeks (n = 43),group B from 2 ~ 6 weeks(n = 67),and group C>6 weeks (n = 51). Complications of three groups were compared and the hydronephrosis after removing double?J stent was recorded. Results The rate of complications of group C was significantly higher than that in group A and group B (P<0.017). However,group A(10/43)has a higher rate of ureterostenosis after removing double?J stent compared with group B(4/67)and group C(3/51),while no statistical significance was observed between group B and group C. Conclusion The incidence of complications after lithotripsy increased with the indwelling time of double?J stent,but the short indwelling time would led to ureterostenosis. Therefore,the optimal indwelling time of double?J stent after flexible ureteroscopy was 2 to 6 weeks,and the indwelling time for patients with injury ureteral mucosa could be appropriately prolonged.

Objective To determine the incidence rate of HPV infection or multi-infections at different stages of cervical lesions in the development of cervical cancer , and the impact of specific types of HPV multi-infections on the risk of cervical cancer. Methods 103 samples of cervical tissues were detected and then divid-ed into ICC/HSIL group and LSIL/NILMF group according to the degree of pathological changes. HPV type was determined by PCR product sequencing. E6 nested multiplex PCR was performed to detect HPV multi-infections. Odds ratios were calculated to determinate the association between the sample category (LSIL/NILM or ICC/HSIL) and the specific types of HPV multi-infections. Results In HPV-positive samples, the rate of multi-in-fections had no significant differences between the two groups. Coinfection of HPV68 with HPV16 increased the risk of ICC/HSIL, as compared with HPV16 or HPV68 infection alone. Conclusions High-risk HPV coinfec-tions has a higher risk to induce ICC/HSIL than does HPV infection alone.

Objective The article aimed to investigate the correlation of lipid profile levels with deoxyribonucleic acid (DNA) damage and total antioxidant capacity (TAC) levels in obese pregnant women. Methods Healthy pregnant women (n=120 ) who took routine prenatal care from August 2011 to August 2012 in our hospital were recruited .All the pregnant women were di-vided into normal weight group ( n =45 ) and obese group ( n=75 ) .The lipid profile levels , DNA damage and TAC levels of two groups were compared and analyzed , and the correlations among lipid profile levels , DNA damage and TAC levels were analyzed . Results Compared to normal weight group , obese group showed significantly higher levels of TC (P=0.000), TG(P=0.000), and LDL-c(P=0.004), but a lower level of HDL-c (P=0.006).The DNA damage and TAC level of obese group were obviously higher than those of normal weight group (P=0.000, P=0.000).The DNA damage was positively correlated with levels of TC , TG and LDL-c among obese pregnant women (r=0.23, P=0.026;r=0.26, P=0.008;r=0.19, P=0.032), and TAC level was positive-ly correlated with TG level (r=0.32,P=0.000). Conclusion Dyslipidemia, imbalance of prooxidant and antioxidant status al-ways occur to obese pregnant women .The DNA damage is positively correlated with levels of TC , TG and LDL-c among obese pregnant women, and TAC is positively correlated with TG level .

Aim To investigate the effect of the total flaconoids extracted from Xiaobuxin-Tan g ( XBXT-2 )
on the hyperactivity of hypothalamic-pituitary-adrenal axis in mouse learned helplessness model. Methods Learned helplessness was induced by inescapable foot shock stress over 1h session for 5 days. After screen-ing, we divided learned helplessness mice into five groups:IS, inescapable shock;Dlx, dulxetine(20 mg ·kg-1);XBXT-2(25,50 mg·kg-1). Latency to es-cape shocks and escape failure had been recorded. During the test, Dlx(20 mg·kg-1 ) and XBXT-2(25, 50 mg·kg-1 ) were administered intragastrically once daily for four days. Serum corticosterone level and ad-renocorticotropic hormone ( ACTH ) level were meas-ured by ELISA, and expression of glucocorticoids re-ceptor ( GR) α/β and brain-derived neurotrophic fac-tor ( BDNF ) in hippocampus was determined using Western blot method. Results XBXT-2 (25,50 mg·
kg-1 ) or duloxetine treatment showed antidepressant effect in mouse learned helplessness model, as demon-strated by the decreased escape failure and escape la-tency. Our ELISA results showed that XBXT-2 or du-loxetine significantly decreased serum corticosterone level and its upstream stress hormone ACTH level in learned helplessness mice. Furthermore, Western blot result demonstrated XBXT-2 treatment increased GRs and BDNF expression in hippocampus. Conclusions XBXT-2 produces significant antidepressant effect on learned helplessness mice. In addition, the modulation of HPA axis produced by XBXT-2 may be important mechanism underlying its antidepressant-like effect in mouse learned helplessness model.