Objective To investigate the effect of angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and AngII receptor (ATR) gene polymorphisms combined with climatic factors on the incidence of essential hypertension (EH) in Tibetan population in Gannan area. Methods A follow-up study was conducted to select 671 Tibetan people in Gannan area who were physically examined in April 2019 at the Health Management Center of the Second Hospital of Lanzhou University and agreed to be enrolled as a fixed cohort, and the blood pressure values of the enrolled subjects were measured after 3.5 years of follow-up, and a total of 501 cases were obtained. At the same time, the peripheral blood of all subjects was collected and the polymorphisms of AGT, ACE and ATR genes were detected by gene chip technology, and the possible interactions were analyzed by logistic regression model, fork generation method and multifactor-dimensionality reduction (MDR). Results Sunshine time was a protective factor for the incidence of hypertension in the Tibetan population of Gannan (OR=0.781), while relative humidity (OR=1.182), air pressure (OR=1.338) and temperature (OR=1.449) were the risk factors for the incidence of hypertension. According to the results of partial correlation analysis, temperature had no effect on the incidence of hypertension after controlling air pressure. There was an additive interaction between high air pressure and the polymorphisms of rs699 (OR=1.650, 95%CI: 1.293-2.399, P<0.001) and rs5049 (OR=1.711, 95%CI: 1.337-4.920, P<0.001) genes of AGT gene; there was a multiplicative interaction between relative humidity and rs699 (OR=0.472, 95%CI: 0.120-0.783, P<0.05);there was a multiplicative interactions between the altitude ≥ 3000m and rs699 (OR=1.503, 95%CI: 1.220-3.174, P<0.01), rs5049 (OR=1.673, 95%CI: 1.380-3.961, P<0.001) or rs2148582 (OR=0.519, 95%CI: 0.284-0.716, P<0.05).However, there was no interaction between climatic factors and ACE or ATR gene polymorphisms on the incidence of hypertension. Conclusion Climatic factors and altitude ≥3 000 m are closely related to the incidence of hypertension in the Tibetan population of Gannan area, and the interaction between AGT gene polymorphisms and climatic factors affects the incidence of hypertension in the population of this area.

OBJECTIVES: To explore the mechanism of Shuangshu Decoction (SSD) for inhibiting growth of gastric cancer xenografts in nude mice. METHODS: Network pharmacology analysis was conducted to identify the common targets of SSD and gastric cancer cell ferroptosis, and bioinformatics analysis and molecular docking were used to validate the core targets. In the cell experiment, AGS cells were treated with SSD-medicated serum, Fer-1 (a ferroptosis inhibitor), or both, and the changes in cell viability, ferroptosis markers (ROS, Fe²⁺ and GSH), expressions of P53, SLC7A11 and GPX4, and mitochondrial morphology were examined. In a nude mouse model bearing gastric cancer xenografts, the effects of gavage with SSD, intraperitoneal injection of Fer-1, or their combination on tumor volume/weight, histopathology, and expressions of P53, SLC7A11 and GPX4 levels were evaluated. RESULTS: The active components in SSD (quercetin and wogonin) showed strong binding affinities to P53. In AGS cells, SSD treatment dose-dependently inhibited cell proliferation, increased ROS and Fe²⁺ levels, upregulated P53 expression, and downregulated the expressions of SLC7A11 and GPX4, but these effects were effectively attenuated by Fer-1 treatment. SSD also induced mitochondrial shrinkage and increased the membrane density, which were alleviated by Fer-1. In the tumor-bearing mouse models, gavage with SSD significantly reduced tumor size and weight, caused tumor cell necrosis, upregulated P53 and downregulated SLC7A11 and GPX4 expression in the tumor tissue, and these effects were obviously mitigated by Fer-1 treatment. CONCLUSIONS SSD inhibits gastric cancer growth in nude mice by inducing cell ferroptosis via the P53/SLC7A11/GPX4 axis.
Ferroptosis/drug effects* ; Animals ; Stomach Neoplasms/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Mice, Nude ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Amino Acid Transport System y+/metabolism* ; Mice ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Xenograft Model Antitumor Assays

Esophageal cancer is an upper gastrointestinal malignancy with a bleak prognosis.It is still being explored in depth due to its complex molecular mechanisms of occurrence and development.Lipids play a crucial role in cells by participating in energy supply,biofilm formation,and signal transduction pro-cesses,and lipid metabolic reprogramming also constitutes a significant characteristic of malignant tu-mors.More and more studies have found esophageal cancer has obvious lipid metabolism abnormalities throughout its beginning,progress,and treatment resistance.The inhibition of tumor growth and the enhancement of antitumor therapy efficacy can be achieved through the regulation of lipid metabolism.Therefore,we reviewed and analyzed the research results and latest findings for lipid metabolism and associated analysis techniques in esophageal cancer,and comprehensively proved the value of lipid metabolic reprogramming in the evolution and treatment resistance of esophageal cancer,as well as its significance in exploring potential therapeutic targets and biomarkers.

Signal transducer and activator of transcription 3(STAT3)is known to modulate the expression of genes related to cell transformation,proliferation,and survival,making it a significant target for cancer therapy.Recent research has also highlighted the crucial involvement of aberrant STAT3 activation in the pathogenesis of diabetic kidney disease(DKD).Accordingly,this article focuses on the therapeutic potential of targeting STAT3 in DKD.The structure of STAT3,its mechanisms of activity regulation,mechanisms of abnormal STAT3 activation in DKD,and a summary of the current research is provided.The review aims provide a reference for research into the pathogenesis of DKD and the development of new drugs.

Objective To explore the effect and mechanism of uric acid(UA)in regulating the larval growth and development of Drosophila melanogaster.Methods A total of 1350 newly hatched first-instar larvae of wild-type Drosophila melanogaster(W11 18)were collected,and the Drosophila melanogaster model of hyperurice-mia was constructed with a high purine diet.The larvae were assigned into three groups(n=150):control(stand-ard corn meal medium),low-dose adenine(corn meal medium containing 0.05％adenine),and high-dose ad-enine(corn meal medium containing 0.10％adenine),and two parallel groups were set up.The growth and de-velopment of larvae in each group was observed,and the UA and hormone levels were measured.In addition,the expression levels of genes involved in growth and development were determined.Results Compared with the con-trol group,the low-and high-dose adenine groups showed elevated UA levels(both P＜0.001)and prolonged de-velopmental period(P=0.024,P＜0.001).The high-dose adenine group showed decreased survival rate,pupa-tion rate,and eclosion rate and elevated levels of juvenile hormone(JH)and 20-hydroxyecdysone(20E)(all P＜0.001).The PCR results showed that compared with the control group,high-dose adenine upregulated the mRNA levels of reactive oxygen species(ROS),forkhead box O(FOXO),and mammalian target of rapamycin(mTOR)while downregulating the mRNA levels of Sestrin,mTOR complex 1(mTORC1),and AMP-activated protein kinase(all P＜0.001).Conclusion High concentrations of UA may promote the expression of ROS/FOXO/mTORC1/mTOR signaling pathway by regulating the levels of JH and 20E,thereby inhibiting the larval growth and development of Drosophila melanogaster.

Objective:To investigate the effects of blood pressure variability (BPV), serum reactive oxygen species (ROS) and superoxide dismutase (SOD) levels on cognitive function in patients with subcortical ischemic vascular disease (SIVD).Methods:A total of 133 patients with SIVD confirmed by craniocranial MRI admitted to Department of Neurology, Red Flag Hospital Affiliated to Mudanjiang Medical University from October 2021 to October 2022 were selected. According to Montreal Cognitive Assessment scores, they were divided into SIVD without cognitive impairment group (SIVD-NC group, n=39) and subcortical vascular cognitive impairment group (SVCI group, n=94); and 23 healthy volunteers with normal cognition who had normal brain MRI in the Physical Examination Center during the same period were chosen as control group. General data of all subjects and vascular risk factors in each group were collected, routine biochemical indexes of peripheral blood were detected, 24 h ambulatory blood pressure monitoring was performed, and serum ROS and SOD levels were detected by enzyme-linked immunosorbent assay. Statistical methods were used to analyze the risk factors for cognitive impairment, correlations of independent risk factors with cognitive function, and diagnostic value of risk factors in cognitive impairment in patients with SIVD. Results:(1) Compared with control group, SIVD-NC group had significantly increased percentages of patients with hypertension history or lacunar stroke history, and significantly increased hypersensitive C-reactive protein (hs-CRP) level ( P<0.05). Compared with control group and SIVD-NC group, patients in SVCI group had significantly older age, lower years of education, higher proportion of patients with lacunar stroke history, and increased hs-CRP level ( P<0.05). Compared with control group, SVCI group had significantly higher proportion of patients with hypertension history ( P<0.05). (2) SIVD-NC group had significantly higher ROS level than control group ( P<0.05); Compared with control group and SIVD-NC group, SVCI group had significantly increased ROS level ( P<0.05). (3) SIVD-NC group had significantly increased nighttime systolic blood pressure (nSBP) compared with control group ( P<0.05); SVCI group had significantly increased 24 h SBP, nSBP and nSBP-variable coefficient (CV) compared with control group and SIVD-NC group ( P<0.05). Compared with SIVD-NC group, SVCI group had significantly increased 24 h SBP-CV ( P<0.05). (4) The nSBP, nSBP-CV, serum hs-CRP and ROS, and lacunar stroke history were independent risk factors for cognitive impairment in SIVD patients ( OR=1.096, P<0.001, 95% CI: 1.042-1.154; OR=1.231, P=0.010, 95% CI: 1.050-1.443; OR=2.303, P=0.004, 95% CI: 1.311-4.039; OR=1.026, P<0.001, 95% CI: 1.014-1.039; OR=2.954, P=0.041, 95% CI: 1.045-8.348), and education level was a protective factor for that ( P<0.05). (5) Serum ROS and hs-CRP, nSBP, and nSBP-CV were negatively correlated with MoCA scores in SIVD patients ( r s=-0.336, P<0.001; r s=-0.503, P<0.001; r s=-0.204, P=0.018; r s=-0.309, P=0.001). (6) Serum ROS and hs-CRP, nSBP, and nSBP-CV had high diagnostic values in cognitive impairment in SIVD patients (areas under the curves: 0.874, 0.847, 0.804 and 0.702, P<0.05); combined diagnosis efficacy of multiple indexes was better (area under the curve: 0.948, P<0.05). Conclusion:Serum ROS and hs-CRP, nSBP and nSBP-CV are highly likely to be hemodynamic and serological monitoring indexes for screening of cognitive impairment in SIVD patients.

Esophageal squamous cell carcinoma is one of the most common malignant tumors in China. Neoadjuvant chemoradiotherapy combined with surgery significantly improved the survival rate of locally advanced operable esophageal squamous cell carcinoma, but approximately half of the patients had poor or no efficacy. To accurately predict the efficacy of neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma and select the dominant population of neoadjuvant chemoradiotherapy, many studies on biomarkers have emerged, which have promoted the progress of neoadjuvant therapy for esophageal squamous cell carcinoma to some extent. In this article, the studies on biomarkers predicting the efficacy of neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma were reviewed.

Pulsed electric field(PEF) provides high-energy instantaneous pulse and release energy to myocardial cell membrane, resulting in irreversible electroporation and causes myocardial cell contents leakage, destruction of intracellular homeostasis, cell death, and slight inflammatory response. PEF as non-thermal energy promotes the design and application of arrhythmia ablation catheter to enter a new stage. There are currently limited clinical studies that have proved the safety and effectieness of Farawave PEF catheter, PVAC GOLD PEF catheter, Lattice-tip Sphere-9 PEF and radiofrequency (RF) catheter used for atrial fibrillation ablation, but still need further discussion. The research of atrial fibrillation ablation with PEF is under study in China. In this paper, the design and application of PEF ablation for tachyarrhythmia are reviewed.
Atrial Fibrillation/surgery* ; Catheter Ablation ; Catheters ; Humans ; Pulmonary Veins/surgery* ; Tachycardia

Objective:To investigate the effect of mannose on the radiosensitivity of six human non-small cell lung cancer cell lines and its possible mechanism.Methods:The expression of mannose phosphate isomerase in six lung cancer cell lines were detected by Western blot. The inhibitory effect of mannose on the proliferation of lung cancer cell lines were observed by MTT assay. When irradiated with 0, 2, 4, 6, 8 and 10 Gy, the effect of mannose on the radiosensitivity of six lung cancer cell lines was detected by plate clone formation assay, respectively; and the apoptosis rates of normal control, mannose, irradiation and combined groups were detected by flow cytometry.Results:The expression levels of mannose phosphate isomerase were different among six lung cancer cell lines. Among them, A549 cells had the highest expression level and H460 cells showed the lowest expression level. When aD ministrated with 11.1 mmol/L mannose, the same inhibitory effect was observed on both A549 and H460 cell lines. Moreover, the inhibitory effect on H460 cell line was significantly increased with the increase of mannose concentration. In addition, aD ministration of 11.1 mmol/L mannose could significantly increase the radiosensitivity and apoptosis rate of H460 cell line. However, it exerted limited effect upon the radiosensitivity and apoptosis rate of A549 cell line. Conclusion:In six lung cancer cell lines with high expression of mannose phosphate isomerase, the aD ministration of mannose can enhance the radiosensitivity of partial tumors cells.

Objective:To evaluate the long-term survival and identify prognostic factors of patients diagnosed with early-stage non-small cell lung cancer (ES-NSCLC) receiving stereotactic ablation radiotherapy (SABR).Methods:Clinical data of 109 ES-NSCLC patients treated with SABR in Henan Cancer Hospital from 2011 to 2018 were retrospectively analyzed. The overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) were calculated by Kaplan- Meier method and log-rank test. Multivariate prognostic analysis was performed by Cox regression model. Results:The median follow-up time was 44 months (2-93 months). The median OS, CSS and PFS were 78 months, 78 months and 44 months, respectively. The 1-year OS, CSS and PFS were 95.4%, 97.2% and 84.1%, and 75.6%, 79.1% and 56.6% for the 3-year OS, CSS and PFS, and 55.6%, 60.7% and 37.3% for the 5-year OS, CSS and PFS, respectively. Univariate analysis showed that ECOG score, age, smoking history and derived-neutrophil/lymphocyte ratio (dNLR) were the influencing factors of OS ( P=0.03, 0.02, 0.04, 0.001). Age, smoking history and dNLR were the influencing factors of CSS ( P=0.02, 0.03, 0.001). Multivariate analysis demonstrated that dNLR was an independent prognostic factor for OS and CSS ( P=0.001, 0.001). Conclusions:ES-NSCLC patients treated with SABR can achieve favorable survival. The dNLR is an independent prognostic factor of OS and CSS, which can be considered in clinical application.