Objective To investigate the effects of ROCK-siRNA transfection on endothelial cell senescence and endothelial microparticles (EMPs) induced by angiotensin II (Ang II). Methods Human umbilical vein endothelial cells (HUVECs) were treated with Ang II (1.0 μmo/L) to induce cellular senescence models, followed by transfection with ROCK-siRNA. The cells were divided into four groups: control group, model group, negative transfection control group (Ang II combined with NC-siRNA), and ROCK-siRNA transfection group (Ang II combined with ROCK-siRNA). Cellular senescence was assessed by SA-β-Gal staining. EMP levels in cell supernatants and intracellular reactive oxygen species (ROS) levels were assessed using flow cytometry. The expression levels of silenced information regulator 1(SIRT1) and p53 protein in each group were analyzed by Western blotting. Results Following ROCK-siRNA transfection, the number of senescent cells induced by Ang II was significantly reduced, accompanied by decreased CD31⁺ EMP levels and suppressed intracellular ROS levels. Meanwhile, the expression levels of SIRT1 were up-regulated, while the expression levels of p53 were down-regulated. Conclusion Silencing ROCK expression suppresses EMP release, reduces ROS generation, regulates the expression of SIRT1 and p53, and ultimately attenuates Ang II-induced endothelial cell senescence.
Humans ; Angiotensin II/pharmacology* ; Cellular Senescence/genetics* ; Human Umbilical Vein Endothelial Cells/cytology* ; RNA, Small Interfering/metabolism* ; Reactive Oxygen Species/metabolism* ; Sirtuin 1/genetics* ; Transfection ; Tumor Suppressor Protein p53/genetics* ; Cell-Derived Microparticles/drug effects* ; rho-Associated Kinases/metabolism* ; Endothelial Cells/metabolism* ; Cells, Cultured

Organ damage from cancer treatment remarkably effects patients’ prognosis and quality of life. In recent years, preventive organ protection strategies, such as interdisciplinary collaboration, early prevention, precision interventions, psychological support, and the integrated application of traditional Chinese medicine, have demonstrated substantial clinical value and achieved notable progress. However, these approaches still encounter multiple challenges. Establishing multidisciplinary teams, optimizing therapeutic balance, and strengthening evidence-based research are essential for addressing the challenges related to treatment balance optimization, multidisciplinary coordination, and clinical translation of novel technologies. This review systematically summarizes recent advancements in preventive organ protection, analyzes existing challenges and potential solutions, and offers forward-looking recommendations. It aims to provide valuable insights for optimizing comprehensive cancer treatment strategies and improving long-term patient outcomes.

To summarize LI Qiangou's clinical experience in treating laryngopharyngeal reflux disease （LPRD） based on the theory of "yang transforming qi while yin constituting form". It is believed that "insufficiency of yang transforming qi and excess of yin constituting form" is the key mechanism of LPRD， in which yang deficiency of the lungs， spleen and kidneys is an important factor causing "insufficiency of yang transforming qi"， while phlegm， dampness and other tangible yin turbidities are the pathological products of "excess of yin constituting form". The key treatment principle is to reinforce yang qi and dispel yin turbidity. Starting from regulating the qi transformation of the sanjiao， the treatment is based on the different pathologies of lung yang insufficiency and phlegm congestion in the upper jiao， spleen yang failing to ascend and dampness accumulation in the middle jiao， and kidney yang deficiency and phlegm-fluid retention in the lower jiao， prescribed by modified Suzi Jiangqi Decoction （苏子降气汤）， Shengyang Chushi Decoction （升阳除湿汤）， and Jingui Shenqi Pill （金匮肾气丸）， the prescriptions could also combine with Banxia Houpo Decoction （半夏厚朴汤） to dissolve phlegm and relieve pharyngeal pains， and regulate qi to direct counterflow downward.

Objective The purpose of this study was to investigate the differences in the anti cyclic fatigue perfor-mance of Woride KS(WKS),Proteper Gold(PTG),and Hyflex CM(HCM)nickel titanium instruments with different tip diameters in curved root canal models,and to provide reference for the targeted selection of suitable nickel titanium in-struments in clinical preparation of curved root canals.Methods Three kinds of new nickel titanium files with 20#and 25#(0.20 mm and 0.25 mm)tip diameters were selected,including WKS(20/0.06),WKS(25/0.06),PTG(20/0.07),PTG(25/0.08),HCM(20/0.06),and HCM(25/0.06),each with 20 files.According to the recommended speed and torque of the motor,the anti cycle fatigue performance of the nickel titanium file was tested in 30° and 60° stainless steel root canal models.The time from rotation to fatigue fracture(TTF)of the nickel titanium file was recorded with a camera and timer,and the fragment length(FL)was measured and recorded with a Vernier scale.Results Com-parison of TTF of the same type of file.① WKS:the TTF of files with the same tip diameter in a 30° curved root canal was longer than 60°(P＜0.05);The TTF of 25# nickel titanium files in the same angle curved root canal was longer than that of 20# nickel titanium files(P＜0.05).②PTG:the 20# nickel titanium files had a TTF longer than 60° in a 30° curved root canal(P＜0.05),while the 25# nickel titanium files had no statistically significant difference in TTF be-tween the 30° curved root canal and 60° curved root canal(P＞0.05);In a 30° curved root canal,the TTF of 20# nickel titanium files was longer than that of 25# nickel titanium files(P＜0.05).In a 60° curved root canal,there were no sta-tistically significant difference between the TTF of 20# nickel titanium files and 25# nickel titanium files(P＞0.05).③HCM:the TTF of files with the same tip diameter in a 30° curved root canal was longer than 60°(P＜0.05);The TTF of 20# nickel titanium files in the same angle curved root canal is longer than that of 25# nickel titanium filea.Compari-son of TTF of different files:in a 30° curved root canal,there was no statistically significant difference in TTF among the three types of 20# nickel titanium files(P＞0.05).The TTF of 25# WKS was longer than that of other files(P＜0.05);In a 60 ° curved root canal,the TTF of 20# HCM was longer than other files with the same tip diameter(P＜0.05),and the TTF of 25# WKS was longer than HCM with the same tip diameter(P＜0.05).The FL of 20# PTG,25#PTG,and 20# HCM in the 30° curved root canal model is significantly longer than that of 60°(P＜0.05),while there is no statistical difference in FL among 20# WKS,25# WKS,and 25# HCM in the 30° and 60° curved root canal models.Conclusion The anti cyclic fatigue performance of WKS is significantly superior to PTG and HCM in a 30° curved root canal.In a 60° curved root canal,20# HCM had a significant advantage in terms of anti cyclic fatigue performance compared to other files,while only 25# WKS had a significant advantage in anti cyclic fatigue performance compared to HCM.

Objective:To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years.Methods:An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster.Results:The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A′s 44.79 (36.94-54.30) ( P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A′s 15.71 (13.24-18.63) ( P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion:Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

Non-small cell lung cancer(NSCLC)is one of the malignant tumors with high morbidity and mortality worldwide.Ferroptosis is a new type of programmed cell death caused by abnormal accumulation of iron-dependent reactive oxygen species(ROS)leading to lipid peroxidation.It involves the balance between iron metabolism,lipid metabolism,oxy-gen free radical reaction and lipid peroxidation.Recent studies have found that ferroptosis is closely related to the occurrence and development of NSCLC.Due to the emergence of chemotherapy resistance and radiotherapy resistance in the treatment of NSCLC,there is an urgent need to develop new effective drugs and treatment strategies.Traditional Chinese medicine has unique advantages in the prevention and treatment of NSCLC due to its multi-targets and minimal side effects.In this review,we summarize the mechanism of ferroptosis in NSCLC,and discuss the research status of active ingredients of traditional Chinese medicine,single-herb traditional Chinese medicine and Chinese herbal compounds in the intervention of NSCLC through ferroptosis,in order to provide a new theoretical basis for the research of ferroptosis pathway and the prevention and treatment of NSCLC by targeted ferroptosis of traditional Chinese medicine.

Objective: To explore the effects of different concentrations of glucose solution on the survival of Aedes albopictus and Culex pipiens pallens larvae, the attraction to mosquitoes and egg-laying behaviors, so as to provide the reference for developing mosquito control technology based on sugar bait. Methods: White porcelain bowls were filled with 100 mL of 3%, 5%, 8%, 10% and 15% glucose solutions. Ten of fourth instar larvae of Aedes albopictus or Culex pipiens pallens were added to each bowl, and the survival of larvae was recorded after 2, 4, 6, 24, 48 and 72 hours. Egg-laying cups containing 5%, 8% and 15% glucose solution were put in mosquito cages containing fully blooded female mosquitoes of Aedes albopictus and Culex pipiens pallens (50 mosquitoes each), and the total number of eggs laid in 72 hours was observed. The analogous site room was filled with fully blooded and starved female mosquitoes of Aedes albopictus and Culex pipiens pallens (100 mosquitoes each), and simple mosquito control buckets containing 5% and 8% glucose solution and black sticky insect plates. The number of mosquitoes and eggs was observed after 6 days. All the above experiments were repeated 3 times using dechlorinated water as the control. Results: The 72 hour corrected mortality rates of Aedes albopictus and Culex pipiens pallens larvae gradually increased with the increase of glucose concentration. The glucose solution with 5% and higher concentrations was not suitable for mosquito larvae to survive. The attraction of egg-laying behaviors to Aedes albopictus and Culex pipiens pallens gradually decreased with the increase of glucose concentration. The effects were similar between 5% and 8% glucose solution, with the averages of 686.67 and 682.33 eggs for Aedes albopictus, and 3.00 and 2.33 egg rafts for Culex pipiens pallens. In analogous site room, there were 93.33, 105.00 and 130.33 adult mosquitoes captured on average in the control group, 5% and 8% glucose solution groups, respectively, with 8% glucose solution group more attractive to adult mosquitoes than the control group (F=3.283, P=0.030); there were 70.33, 55.33 and 63.00 Aedes albopictus eggs (eggs counts+larvae counts) on average, respectively, with statistically significant differences among the three groups (H=6.761, P=0.034). Conclusion Glucose solution with concentration of 5% or higher can effectively inhibit the survival of Aedes albopictus and Culex pipiens pallens larvae, and attractive to adult mosquitoes and egg-laying behavoirs.

Objective:To retrieve, evaluate and integrate the relevant evidence of prevention of lower limb ischemic complications in venous-arterial extracorporeal membrane oxygenation (VA-ECMO) patients, and provide reference for the development of scientific and complete prevention and management of lower limb ischemic complications.Methods:According to the evidence-based methodology, clinical decisions, guidelines, expert consensus, evidence summary, systematic review, randomized controlled trials and experimental studies related to lower limb ischemia complications in VA-ECMO patients were searched from CNKI, Wanfang, PubMed, Cochrane Library and other domestic and foreign databases as well as relevant professional websites. The literature search period was from the establishment of the database to August 2023. Two researchers independently evaluated the literature quality, and then extracted and summarized the evidence according to the theme.Results:A total of 27 004 articles were obtained in the preliminary search, and 11 articles were finally included after screening, including 1 guide, 2 expert consensus, 2 systematic reviews and 6 original studies. Through literature reading, evidence extraction and classification, and expert group meetings, a total of 24 best evidences were concluded in four dimensions, including team training and management, VA-ECMO pre-computer evaluation, VA-ECMO catheter selection, and the monitoring and management of lower limb ischemia.Conclusions:This study summarized the best evidence for the prevention of lower limb ischemia complications associated with VA-ECMO patients, and can provide reference for healthcare providers in clinical practice. In order to ensure the safety of VA-ECMO treatment and reduce the incidence of related complications, healthcare professionals should carefully select and apply evidence according to the clinical context and patients′ wishes.

BACKGROUND:The application of orthodontic force triggers autophagy in the periodontal tissue via diverse signaling pathways,augmenting or attenuating the activity of relevant cell types such as periodontal ligament cells,osteocytes,osteoclasts,and osteoblasts,thus facilitating the process of periodontal remodeling. OBJECTIVE:To review the research progress in orthodontic force mediated autophagy in periodontal tissue and its impact on orthodontic tooth movement. METHODS:The PubMed,Web of Science,China Biology Medicine disc and CNKI were searched for literature published from 2010 to 2023 to summarize the progress in orthodontics-related autophagy.And 76 papers were finally included in the analysis and discussion. RESULTS AND CONCLUSION:Orthodontic force can trigger a series of biochemical signal changes through periodontal mechanical receptors and aseptic inflammation they cause,leading to autophagy in periodontal tissue.Subsequently,autophagy generates corresponding feedback through cascaded amplified signaling pathways such as Phosphoinositide 3-kinase/protein kinase B,Hippo,and mitogen-activated protein kinase pathways,promoting periodontal tissue remodeling and ultimately achieving tooth movement and stability.Orthodontic force-induced autophagy can differentially regulate bone resorption on the tooth pressure side and bone formation on the tension side.Related targets have good prospects in the clinical application of orthodontic treatment.Orthodontics and autophagy have complex mechanisms.However,existing research has only focused on exploring the role of autophagy in orthodontic tooth movement.Further exploration is needed to investigate the mutual regulatory effects between autophagy and orthodontic tooth movement,as well as the interactions between upstream mechanical receptors and signaling pathways involved in related pathways.

AIM:To explore the effects of CD38 on lysosome reformation and cholesterol efflux in macro-phages.METHODS:Bone marrow-derived macrophages from low-density lipoprotein(LDL)receptor knockout(LDLr-/-)mice were cultured as cell model.Live cell imaging system was applied to evaluate the effect of nicotinic acid adenine di-nucleotide phosphate(NAADP)on lysosome number.ELISA was conducted to measure NAADP level in macrophages.After the cells were treated with nicotinic acid(NA),RT-qPCR was conducted to detect CD38 mRNA expression,and Western blot was conducted to observe CD38 protein expression and phosphorylated transcription factor EB(TFEB)level.Laser scanning confocal microscopy was applied to evaluate the influence of CD38/NAADP signaling on lysosome number and cholesterol egression.RESULTS:NAADP remarkably increased lysosome number(P<0.05),and this effect was significantly inhibited by NAADP antagonist NED-19,Ca2+ chelator BAPTA,and calcineurin inhibitor CsA(P<0.05).CD38 markedly enhanced NAADP synthesis in macrophages(P<0.05).NAADP synthetic substrate NA prominently ele-vated the expression of CD38 mRNA and protein(P<0.05).NA significantly decreased the phosphorylated TFEB level;this effect was also attenuated by NED-19,BAPTA and CsA(P<0.05).Disrupting CD38/NAADP signaling pathway markedly inhibited NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux in macrophages(P<0.05).NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux abolished in LDLr/CD38 DKO macrophages(P<0.05),whereas these effects induced by NA were recovered after CD38 gene rescue.CONCLUSION:CD38 triggers lysosome reformation via TFEB and consequently pro-motes the efflux of lysosomal free cholesterol and cytosol cholesterol ester.