Among tumor microenvironment (TME), the entire metabolic characteristics of tumor-resident cells are reprogrammed to benefit the expansion of tumor cells, which count on glutamine in large part to fuel the tricarboxylic acid cycle for energy generation and anabolic metabolism support. Endothelial cells that are abducted by tumor cells to form a pathological tumor vascular network for constructing the hypoxic immunosuppressive TME, also rely on glutaminolysis as the "engine" of angiogenesis. Additionally, the glutamine metabolic preference benefits the polarization of TAMs towards pro-tumoral M2 phenotype as well. Herein, we developed a type of siRNA micelleplexes (MH@siGLS1) to reverse immunosuppressive TME by targeting glutaminolysis within tumor-resident cells for tumor vasculature normalization- and TAMs repolarization-enhanced photo-immunotherapy. Tumor cell starvation and antioxidant system destruction achieved by MH@siGLS1-mediated glutaminolysis inhibition could promote photodynamic therapy efficacy, which was available to trigger immunogenic cell death for adaptive antitumor immune responses. Meanwhile, glutaminolysis inhibition of tumor endothelial cells and TAMs could realize tumor vascular normalization and TAMs repolarization for antitumor immunity amplification. This study provides a unique perspective on cancer treatments by focusing on the interrelations of metabolic characteristics and the biofunctions of various cell types within TME.

OBJECTIVE To investigate the inhibitory effect and mechanism of the active components of Alpinia katsumadai （ACAK） on tumor xenograft growth and tumor angiogenesis of human pancreatic cancer PANC-1 cells in nude mice. METHODS A tumor xenograft model in nude mice was established using human pancreatic cancer PANC-1 cells. The mice were randomly divided into model control group （intragastric administration of 0.9% normal saline）， solvent control group （intragastric administration of 0.5% carboxymethyl cellulose sodium）， positive control group （intraperitoneal injection of 0.5% carboxymethyl cellulose sodium+bevacizumab suspension 5 mg/kg ）， and ACAK 50， 100， and 200 mg/kg groups （intragastric administration of 0.5% carboxymethyl cellulose sodium+ACAK suspension 50， 100， 200 mg/kg）. The administration was carried out for 5 consecutive days followed by a 2-day interval， and this cycle was repeated for a total duration of 28 days. The tumor volume （TV）， relative tumor volume （RTV）， and relative tumor proliferation rate （T/C） at various time points from day 1 to day 28 after drug administration were measured and calculated for each group of nude mice. After the drug administration， the tumor weights were measured， and microvessel density （MVD） in the tumor xenograft tissues of nude mice， as well as relative protein expression levels of vascular endothelial growth factor （VEGF） and its receptor [fas-like tyrosine kinase-1 （Flt-1）， kinase insert domain receptor （KDR）] were detected. RESULTS On the 24th day of ACAK administration，compared with the model control group， the TV and RTV （except for ACAK 50 and 100 mg/kg groups） of nude mice in the positive control group and ACAK dose groups were significantly decreased （P＜0.05 or P＜0.01）， and the T/C of ACAK dose groups showed a dose-dependent decrease； the microvascular distribution of nude mice in the positive control group and ACAK dose groups was relatively sparse， and the tumor weight （except for the ACAK 50 mg/kg group）， MVD， and relative expression levels of VEGF， KDR， and Flt-1 in the tumor xenograft tissues were significantly reduced （P＜0.05 or P＜0.01）. CONCLUSIONS ACAK has a good anti-pancreatic cancer effect， and its mechanism may be related to its inhibition of VEGF/ VEGFR signaling pathway， thereby inhibiting angiogenesis in pancreatic cancer.

Prolonged disorders of consciousness(pDoC)are complex and prolonged conditions that severely impact patient prognosis and remain a clinical treatment challenge.In recent years,neural regulation-based awakening therapies have been widely applied in the assessment and treatment of pDoC patients.Repetitive transcranial magnetic stimulation(rTMS)technology can regulate neural activity and improve patients'consciousness states,demonstrating positive awakening effects for pDoC patients.However,the optimal stimulation parameters and awakening mechanisms of rTMS remain unclear.This article reviews the pathological mechanisms of pDoC,clinical applications of rTMS at different targeting sites and stimulation frequencies,and focuses on exploring how rTMS promotes consciousness recovery through neural mechanisms such as altering neural pathways,reshaping brain networks,promoting synaptic plasticity and neurotransmitter release,regulating neurotrophic factor expression,and modulating cerebral hemodynamics.Based on artificial intelligence,the article also prospects the future clinical research applications of rTMS.

Objective:To explore the prevalence and risk factors of insomnia in Chinese Air Force servicemen deployed to highland areas.Methods:A total of 718 Air Force servicemen deployed to Qinghai-Tibetan plateau were recruited at May 2024.Sleep quality was assessed with the Pittsburgh Sleep Quality Index.Social-demograph-ic,military service,and psychological characteristics were measured with a self-administered general question-naire.Bivariable and multivariable logistic regressions were performed to identify independent risk factors.Missing data were handled by the multiple imputation.Results:The average sleep duration was(6.9±1.2)h and the aver-age PSQI score was(5.9±4.1).Totally 53.8％of participants experienced clinically significant insomnia.The multivariable analysis revealed that age≥35(aOR=4.07,95％CI=1.11-17.76),stressful event(aOR=3.27,95％CI=2.00-5.49),dysfunctional sleep beliefs and attitudes(aOR=2.59,95％CI=1.75-3.85),and caffeine product usage(aOR=1.69,95％CI=1.17-2.43)were risk factors for insomnia,while Tibetan-indigenous ethnic(aOR=0.44,95％CI=0.20-0.91),higher perceived social support(aOR=0.96,95％CI=0.96-0.99),and positive coping style(aOR=0.96,95％CI=0.93-0.99)were protective factors.Conclusion:Air force service-men deployed to highland areas have sufficient sleep time,but reduced sleep quality.Age,exposed to stress event during deployment,dysfunctional sleep beliefs and attitudes,and caffeine product usage are risk factors for insomni-a,while Tibetan-indigenous ethnic,higher perceived social support and positive coping style act as protective fac-tors.

Objective:To preliminarily evaluate the efficacy and safety of a domestically developed bilateral interventional ultrasound renal denervation (RDN) system in patients with uncontrolled hypertension despite antihypertensive medication.Methods:A multicenter, single-arm trial was conducted. Patients with uncontrolled hypertension (≥2 antihypertensive drugs) were enrolled from April 2023 to April 2024 at the Second Affiliated Hospital of Chongqing Medical University, West China Hospital of Sichuan University, and the Second Affiliated Hospital of Harbin Medical University. RDN was performed using the UltraCure? bilateral interventional ultrasound system via femoral or brachial artery access. Multi-segmental "quadrant-based" ablation was performed in bilateral main renal arteries and branches/accessory arteries (diameter≥4 mm). Primary endpoints were changes in office systolic blood pressure (SBP) and 24-hour daytime SBP at 2-and 6-months post-procedure. The primary safety endpoints included the incidence of major adverse events, device-related adverse events, and puncture site complications.Results:Ten patients, mean aged 47.1 years, including 9 male, successfully completed RDN. At 2 and 6 months post-procedure, office SBP decreased by (19.7±15.2) mmHg ( P=0.002, 1 mmHg=0.133 kPa) and (13.8±13.9) mmHg ( P=0.013) from baseline, while the 24-hour daytime SBP decreased by (13.4±10.6) mmHg ( P=0.004) and (11.2±9.2) mmHg ( P=0.004). Apart from one case of a limited distal renal artery dissection, no other serious device/procedure-related adverse events were observed. At 6-month follow-up, the estimated glomerular filtration rate remained stable ((85.3±18.3) ml·min -1·1.73 m -2 vs. (82.3±19.2) ml·min -1·1.73 m -2, P=0.41). No renal artery stenosis was detected. Conclusions:The domestic interventional ultrasound RDN system could effectively reduce office and ambulatory blood pressure in patients with uncontrolled hypertension, demonstrating a favorable safety profile. Long-term efficacy requires confirmation through large-scale randomized controlled trials.

BACKGROUND:Marine traditional Chinese medicine offers a potentially effective and less adverse treatment for osteoporosis.OBJECTIVE:To explore the pharmacological regulations and procedures of traditional Chinese medicine in treating osteoporosis through data mining and network pharmacology techniques.METHODS:Data mining and network pharmacology methods were used to study the medication pattern and mechanism of marine Chinese medicine patented prescriptions approved by China National Intellectual Property Administration for the treatment of osteoporosis,and special attention was paid to the core Chinese medicine constituents of these prescriptions.The core constituents of the compound drug group composed of oyster-Dipsacus asper-epimedium were comprehensively identified and analyzed by using ultra-high-performance liquid chromatography tandem mass spectrometry.RESULTS AND CONCLUSION:(1)We collected 381 authorized compound patents for the treatment of osteoporosis from the database inception to April 1,2024.Among these,48 patent groups utilized marine traditional Chinese medicine.These prescriptions contained 183 Chinese herbal medicines,of which 13 marine traditional Chinese medicines were used 574 times in total,and the number of flavors used in a single patented formula ranged from 2 to 41.(2)Oyster was the most frequently used marine ingredient,while Dipsacus asper,epimedium,Rehmannia glutinosa,Eucommia ulmoides Oliv.were the most frequent non-marine components.Association rule analysis identified oyster,Dipsacus asper,and epimedium as the core drug group.Network pharmacology analysis revealed that the core targets of this group for the treatment of osteoporosis included ALB,AKT1,TP53,PPARG,and SRC.Sitosterol,liquiritigenin,japonine,luteolin,and kaempferol were identified as the core components within the marine traditional Chinese medicine prescriptions.(3)The GO and KEGFG enrichment analyses suggested a potential association between the mechanism of the core drug group and the rap1/mapk signaling pathway in the treatment of osteoporosis.(4)The molecular docking verified the beneficial interactions between core components and core targets.(5)The ultra-high-performance liquid chromatography tandem mass spectrometry analysis of the compound medicine confirmed the presence of luteolin,sitosterol,kaempferol,and other components,aligning with the drug components identified by network pharmacology.Quantitative analysis indicated that flavonoids,terpenes,and alkaloids constituted a significant proportion of the compound medicine's components.

Objective:To explore the prevalence and risk factors of insomnia in Chinese Air Force servicemen deployed to highland areas.Methods:A total of 718 Air Force servicemen deployed to Qinghai-Tibetan plateau were recruited at May 2024.Sleep quality was assessed with the Pittsburgh Sleep Quality Index.Social-demograph-ic,military service,and psychological characteristics were measured with a self-administered general question-naire.Bivariable and multivariable logistic regressions were performed to identify independent risk factors.Missing data were handled by the multiple imputation.Results:The average sleep duration was(6.9±1.2)h and the aver-age PSQI score was(5.9±4.1).Totally 53.8％of participants experienced clinically significant insomnia.The multivariable analysis revealed that age≥35(aOR=4.07,95％CI=1.11-17.76),stressful event(aOR=3.27,95％CI=2.00-5.49),dysfunctional sleep beliefs and attitudes(aOR=2.59,95％CI=1.75-3.85),and caffeine product usage(aOR=1.69,95％CI=1.17-2.43)were risk factors for insomnia,while Tibetan-indigenous ethnic(aOR=0.44,95％CI=0.20-0.91),higher perceived social support(aOR=0.96,95％CI=0.96-0.99),and positive coping style(aOR=0.96,95％CI=0.93-0.99)were protective factors.Conclusion:Air force service-men deployed to highland areas have sufficient sleep time,but reduced sleep quality.Age,exposed to stress event during deployment,dysfunctional sleep beliefs and attitudes,and caffeine product usage are risk factors for insomni-a,while Tibetan-indigenous ethnic,higher perceived social support and positive coping style act as protective fac-tors.

BACKGROUND:Marine traditional Chinese medicine offers a potentially effective and less adverse treatment for osteoporosis.OBJECTIVE:To explore the pharmacological regulations and procedures of traditional Chinese medicine in treating osteoporosis through data mining and network pharmacology techniques.METHODS:Data mining and network pharmacology methods were used to study the medication pattern and mechanism of marine Chinese medicine patented prescriptions approved by China National Intellectual Property Administration for the treatment of osteoporosis,and special attention was paid to the core Chinese medicine constituents of these prescriptions.The core constituents of the compound drug group composed of oyster-Dipsacus asper-epimedium were comprehensively identified and analyzed by using ultra-high-performance liquid chromatography tandem mass spectrometry.RESULTS AND CONCLUSION:(1)We collected 381 authorized compound patents for the treatment of osteoporosis from the database inception to April 1,2024.Among these,48 patent groups utilized marine traditional Chinese medicine.These prescriptions contained 183 Chinese herbal medicines,of which 13 marine traditional Chinese medicines were used 574 times in total,and the number of flavors used in a single patented formula ranged from 2 to 41.(2)Oyster was the most frequently used marine ingredient,while Dipsacus asper,epimedium,Rehmannia glutinosa,Eucommia ulmoides Oliv.were the most frequent non-marine components.Association rule analysis identified oyster,Dipsacus asper,and epimedium as the core drug group.Network pharmacology analysis revealed that the core targets of this group for the treatment of osteoporosis included ALB,AKT1,TP53,PPARG,and SRC.Sitosterol,liquiritigenin,japonine,luteolin,and kaempferol were identified as the core components within the marine traditional Chinese medicine prescriptions.(3)The GO and KEGFG enrichment analyses suggested a potential association between the mechanism of the core drug group and the rap1/mapk signaling pathway in the treatment of osteoporosis.(4)The molecular docking verified the beneficial interactions between core components and core targets.(5)The ultra-high-performance liquid chromatography tandem mass spectrometry analysis of the compound medicine confirmed the presence of luteolin,sitosterol,kaempferol,and other components,aligning with the drug components identified by network pharmacology.Quantitative analysis indicated that flavonoids,terpenes,and alkaloids constituted a significant proportion of the compound medicine's components.

Objective:To preliminarily evaluate the efficacy and safety of a domestically developed bilateral interventional ultrasound renal denervation (RDN) system in patients with uncontrolled hypertension despite antihypertensive medication.Methods:A multicenter, single-arm trial was conducted. Patients with uncontrolled hypertension (≥2 antihypertensive drugs) were enrolled from April 2023 to April 2024 at the Second Affiliated Hospital of Chongqing Medical University, West China Hospital of Sichuan University, and the Second Affiliated Hospital of Harbin Medical University. RDN was performed using the UltraCure? bilateral interventional ultrasound system via femoral or brachial artery access. Multi-segmental "quadrant-based" ablation was performed in bilateral main renal arteries and branches/accessory arteries (diameter≥4 mm). Primary endpoints were changes in office systolic blood pressure (SBP) and 24-hour daytime SBP at 2-and 6-months post-procedure. The primary safety endpoints included the incidence of major adverse events, device-related adverse events, and puncture site complications.Results:Ten patients, mean aged 47.1 years, including 9 male, successfully completed RDN. At 2 and 6 months post-procedure, office SBP decreased by (19.7±15.2) mmHg ( P=0.002, 1 mmHg=0.133 kPa) and (13.8±13.9) mmHg ( P=0.013) from baseline, while the 24-hour daytime SBP decreased by (13.4±10.6) mmHg ( P=0.004) and (11.2±9.2) mmHg ( P=0.004). Apart from one case of a limited distal renal artery dissection, no other serious device/procedure-related adverse events were observed. At 6-month follow-up, the estimated glomerular filtration rate remained stable ((85.3±18.3) ml·min -1·1.73 m -2 vs. (82.3±19.2) ml·min -1·1.73 m -2, P=0.41). No renal artery stenosis was detected. Conclusions:The domestic interventional ultrasound RDN system could effectively reduce office and ambulatory blood pressure in patients with uncontrolled hypertension, demonstrating a favorable safety profile. Long-term efficacy requires confirmation through large-scale randomized controlled trials.

Different pathologic features of vulnerable plaques may display heterogeneous ultrasonic performances during the formatting or developing procedures.Combined application of multimodal ultrasound technology is efficient for evaluating plaque components and assessing the vulnerability of plaques through analyzing various ultrasonic manifestations,having unique advantages and development potential for predicting the risk of ischemic stroke,guiding early clinical intervention,evaluating the efficacy and prognosis and so on.The research progresses of multimodal ultrasound technology for assessing the vulnerability of carotid atherosclerotic plaques were reviewed in this article.