AIM:To investigate the effect of fibroblast growth factor 21(FGF21)on high glucose-induced oxidative stress in retinal pigment epithelial(RPE)cells and to clarify the underlying molecular mechanisms.METHODS:Single-cell sequencing data from the GEO database were analyzed to determine the expression profile of the FGF21 receptor FGFR1 in RPE cells. Human ARPE-19 cells were cultured and randomly assigned to control, high glucose(30 mmol/L), and high glucose+FGF21 analog treatment groups, with additional siFGFR1 and PI3K inhibitor groups. Cell viability in different treatment groups was assessed using CCK-8 assay, intracellular reactive oxygen species(ROS)levels were quantified using DCFH-DA fluorescent probing combined with immunofluorescence staining and flow cytometry. Transcriptome sequencing was performed on cells from the high glucose group and high glucose+FGF21 group to analyze the enrichment level of the PI3K/Akt signaling pathway. Western blotting was performed to detect phosphorylation levels of PI3K/Akt pathway components.RESULTS:Single-cell sequencing revealed specific expression of FGFR1 in RPE cells of retinal tissues from diabetic model mice. Under In vitro experiments, high glucose(30 mmol/L)exposure reduced ARPE-19 cell viability by 49.7% and increased ROS levels by approximately 2-fold. Whereas treatment with the FGF21 analog(60 ng/mL)restored cell viability and attenuated high glucose-induced ROS accumulation. Mechanistic studies demonstrated that FGFR1 knockdown inhibited the antioxidative stress of FGF21. Further validation of the molecular mechanism revealed that high glucose significantly suppressed the PI3K/Akt pathway activation(the levels of p-Akt and p-PI3K were decreased by 33.9% and 36.6%, respectively), while FGF21 effectively reversed this inhibitory effect and restored the expression of p-Akt and p-PI3K. Treatment with the PI3K inhibitor LY294002 inhibited the cytoprotective effect of FGF21 and significantly increased the ROS-positive cells, these findings confirm that PI3K/Akt signaling is indispensable downstream mechanism for FGF21 to exert its effects.CONCLUSION:FGF21 alleviates high glucose-induced oxidative stress and cellular injury in RPE cells by activating the PI3K/Akt signaling pathway through its receptor FGFR1.

Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1 : 1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.001). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.

[摘 要] 目的：探讨异位表达血红蛋白亚基（HBA/HBB）对缺氧条件下嵌合抗原受体T细胞（CAR-T细胞）功能障碍的改善作用及其对肿瘤细胞的杀伤效应。方法：全基因合成技术合成靶向HER2的CAR序列，构建共表达HBA或HBB的CAR慢病毒载体，包装慢病毒后感染人原代T淋巴细胞，制备异位表达HBA/HBB的CAR-T细胞，命名为HBA CAR-T和HBB CAR-T。采用缺氧探针检测小鼠实体瘤缺氧状态。通过流式细胞术检测瘤内CAR-T细胞占比、异位表达血红蛋白亚基的CAR-T细胞阳性率及CAR-T细胞的活性氧、凋亡水平。WB法检测HBA CAR-T和HBB CAR-T内相关血红蛋白亚基表达情况，采用细胞计数板计数检测细胞增殖水平，通过萤光素酶报告基因法检测CAR-T细胞对肿瘤细胞的杀伤能力，qPCR检测CAR-T细胞中缺氧诱导因子-1α（HIF-1α）表达水平，利用MitoXpress Intra试剂盒检测CAR-T细胞内氧气含量。结果：不同细胞构建的实体瘤模型均存在明显缺氧情况，且CAR-T细胞浸润水平与缺氧程度呈显著负相关（P < 0.000 1）。HBA CAR-T与HBB CAR-T构建成功（阳性率 > 60%），相应血红蛋白亚基可稳定表达。缺氧环境下HBA CAR-T和HBB CAR-T的ROS水平、凋亡水平显著下降，增殖、对肿瘤细胞的体外杀伤能力显著强于传统CAR-T细胞（均P < 0.05）。HBA CAR-T与HBB CAR-T内HIF-1α表达降低（均P < 0.001），且缺氧程度显著降低（均P < 0.001）。结论：异位表达血红蛋白亚基可改善缺氧条件下CAR-T细胞功能障碍并增强其对肿瘤细胞的体外杀伤作用。

Objective: To investigate the effects of clinical routine X-ray irradiation dose (average irradiation dose: 29.7±0.54 Gy) on the function, apoptosis, activation state and mitochondrial function of platelets during in vitro storage, so as to provide experimental evidence for optimizing platelet irradiation strategies. Methods: A paired experimental design was adopted. Platelets were collected from 12 healthy donors, and each sample was equally divided into the irradiated group and the control group (non-irradiated). All samples were stored for 5 days under standard platelet preservation conditions (22±2℃, continuous oscillation). Flow cytometry was used to detect platelet count, apoptosis rate (Annexin V+ positive rate), activation markers (CD62P, PAC-1, CD42b) and reactive oxygen species (ROS) level. Meanwhile, mitochondrial-specific probes were used to evaluate changes in mitochondrial count, membrane potential and adenosine triphosphate (ATP) content. Additionally, transmission electron microscopy (TEM) was employed to observe the ultrastructure of platelets, with a focus on mitochondrial morphology, platelet membrane integrity and granule distribution. Results: Within 5 days of storage, the platelet count was (841±89.16)×10 /L in the irradiated group and (824.5±92.88)×10 /L in the control group, with no statistically significant difference between the two groups (P=0.54). The apoptosis rate was (4.94±1.39) % in the irradiated group and (5.50±0.83) % in the control group, showing no significant difference (P=0.31). For activation indicators, the CD62P expression rate was (24.32±7.57) % in the irradiated group versus (25.21±8.13) % in the control group (P=0.43). The PAC-1 positive rates were (12.15±4.43) % and (11.75±3.40) % in the irradiated group and control group, respectively (P=0.44). The CD42b expression rates were (12.14±4.43) % and (11.75±3.4) % in the two groups, respectively (P=0.47). The ROS levels were (31.98±8.1) % and (30.64±5.89) % in the two groups, respectively (P=0.45). No significant differences were found in the above indicators. For mitochondrial function indicators, the mitochondrial count was (55.88±11.49) % in the irradiated group and (53.5±7.24) % in the control group (P=0.57). The ATP contents were (42.45±5.29) % and (41.58±9.50) % in the irradiated group and control group, respectively (P=0.77). The relative membrane potential values were (59.53±10.89) % and (57.49±6.54) % in the two groups, respectively (P=0.47). No significant difference were observed on the mitochondrial function-related indicators. TEM further confirmed that the ultrastructure of platelets in the irradiation group was intact, the mitochondrial morphology was normal, and no pathological changes such as swelling or vacuolization were observed. Conclusion: This study evaluated the impact of conventional-dose X-ray irradiation on platelet storage quality, confirming that this dose does not significant impair platelet count, apoptosis rate, activation status, or mitochondrial function. This finding provides important experimental evidence for the clinical promotion of X-ray irradiation technology and suggests its potential as a safe alternative to γ irradiation. Future studies could further expand the sample size and extend the observation period to verify the effects of X-ray irradiation on long-term platelet storage and post-transfusion in vivo survival rate.

AIM: To explore the factors affecting the whole-eye astigmatism after pterygium excision combined with autologous limbal stem cell transplantation.METHODS: A retrospective analysis was conducted on the medical records of 42 patients(42 eyes)with primary pterygium admitted in the ophthalmology department of Xijing Hospital from January 2023 to October 2023. They underwent pterygium excision combined with autologous limbal stem cell transplantation. The maximum invasion depth of pterygium into the cornea was measured with anterior segment optical coherence tomography(AS-OCT)before operation, the length of the pterygium invading cornea, the width of the limbus and the area of the invading cornea were measured during the operation, and three-dimensional values of corneal astigmatism of anterior segment, index of surface variance(ISV), index of vertical asymmetry(IVA), best corrected visual acuity(BCVA)and whole-eye astigmatism were collected before and at 1 mo after surgery. Patients with astigmatism ≤0.50 D or >0.50 D of the whole eye at 1 mo after surgery were assigned to group A and B, respectively. The differences of clinical data before and at 1 mo after surgery between the two groups, and the correlation between pre-operative clinical indicators and whole-eye astigmatism were analyzed. The decision tree algorithm was performed to explore the influencing factors of whole-eye astigmatism at 1 mo postoperatively.RESULTS: The maximum invasion depth of pterygium in the group A was significantly less than that in the group B [80.00(40.00, 180.00)μm vs 175.00(123.00, 190.00)μm, P=0.002]. Preoperative BCVA(LogMAR), whole-eye astigmatism, cornea astigmatism, ISV, IVA and maximum invasion depth of pterygium were positively correlated with whole-eye astigmatism at 1 mo after surgery(rs=0.317, P=0.041; rs=0.545, P<0.001; rs=0.448, P=0.003; rs=0.389, P=0.011; rs=0.382, P=0.013; rs=0.391, P=0.010). The decision tree algorithm screened out two influential factors: the maximum invasion depth of pterygium into the cornea and preoperative whole-eye astigmatism. The risk of whole-eye astigmatism >0.50 D at 1 mo after operation was higher with maximum invasion depth of pterygium into the cornea >95 μm than that with ≤95 μm. Among the patients with whole-eye astigmatism >2.63 D before operation, the probability of residual whole-eye astigmatism >0.50 D was 88.9%, and the predictive model AUC was 0.804.CONCLUSION: The whole-eye astigmatism after pterygium resection is mainly affected by the maximum invasion depth of pterygium into the cornea and preoperative whole-eye astigmatism. When the maximum invasion depth of pterygium into the corneal is >95 μm and the whole-eye stigmatism is >2.63 D before surgery, the patient should receive surgical treatment as soon as possible in order to obtain good clinical benefits.

[Objective] To explore the clinical features of IgG4-related urinary diseases so as to provide reference for the diagnosis and treatment of such diseases. [Methods] The clinical data of 4 cases of IgG4-related urinary system diseases diagnosed and treated in Xijing Hospital of Air Force Medical University during Aug.2019 and Dec.2023 were retrospectively collected.Here, we report on the diagnosis and treatment of these patients, analysing their symptoms, serology, imaging and pathology as well as their treatment and outcomes. [Results] The patients included 2 male and 2 female.The lesions were involved with the retroperitoneum and urinary system.Three patients had symptoms of lumbar pain.The imaging manifestations were complex, including retroperitoneal mass involving urinary system organs in 2 cases, tabdense shadow of the right kidney in 1 case, and simple cystic mass of kidney in 1 case.Serum IgG4 value was not detected before surgery.All patients underwent radical surgical treatment.Postoperative pathology showed fibrous tissue hyperplasia with a large number of plasma cells, lymphocytes, a few neutrophil infiltrates, and lymphoid follicles and obliterated vasculitis in some specimens.The number of IgG4⁺ plasma cells was more than 10 in all tissues under high power microscope.After surgery, 3 patients had symptoms improved, and serum IgG4 value was within the normal range; 1 patient (patem 3) had elevated IgG4 value during follow-up, received subsequent hormone therapy, and the serum IgG 4 level remained stable. [Conclusion] The symptoms of IgG4-related diseases involving the urinary system are non-specific, and the imaging findings are various, easily confused with other diseases.Early detection of serum IgG4 and biopsy pathology can help clinicians make correct diagnosis in the early stage.

Objective To explore the dietary nutrition status and nutritional intervention strategy of patients with Alzheimer’s disease (AD). Methods Among the 1 332 patients with AD diagnosed at Xijing Hospital from January 2021 to December 2023 were enrolled as the study subjects. The dietary intake data of patients were collected through questionnaire surveys and dietary reviews. During the study period, 30 patients did not complete the intervention due to withdrawal or loss of follow-up. Based on the actual number of people who completed the intervention, AD patients were randomly divided into intervention group (n=651, individualized nutritional intervention strategy) and control group (n=651, routine nutritional intervention), and both groups were intervened for 3 months. The cognitive function (MMSE score and MoCA score), nutritional status (MNA scale, NRS-2002 scale), and quality of life (GQOL-74) of the two groups of AD patients were compared to evaluate the effectiveness of the intervention strategies. Results A total of 1 332 questionnaires were distributed, and 1 302 valid questionnaires were finally recovered, with an effective recovery rate of 97.75% (1 302/1 332). The survey results showed that there were no statistical differences in baseline characteristics and dietary nutrition status between the two groups of AD patients before intervention (P>0.05). After nutritional intervention, the cognitive function, quality of life, and nutritional status of patients in the intervention group were significantly improved. The MMSE score, MoCA score, MNA score, and GQOL-74 score of the intervention group were significantly higher than those of the control group, while the NRS-2002 score was lower than that of the control group (P<0.05). Conclusion Nutritional intervention strategy has a significant effect on improving nutritional status, cognitive function, and quality of life of AD patients.

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Normal heart function depends on complex regulation by the brain, and abnormalities in the brain‒heart axis affect various diseases, such as myocardial infarction and anxiety disorders. However, systematic tracking of the brain regions associated with the input and output of the heart is lacking. In this study, we injected retrograde transsynaptic pseudorabies virus (PRV) and anterograde transsynaptic herpes simplex virus (HSV) into the left ventricular wall of mice to identify the whole-brain regions associated with the input to and output from the heart. We successfully detected PRV and HSV expression in at least 170 brain subregions in both male and female mice. Sex differences were discovered mainly in the hypothalamus and medulla, with male mice exhibiting greater correlation and hierarchical clustering than female mice, indicating reduced similarity and increased modularity of virus expression patterns in male mice. Further graph theory and multiple linear regression analysis of different injection timelines revealed that hub regions of PRV had highly similar clusters, with different brain levels, suggesting a top-down, hierarchically transmitted neural control pattern of the heart. Hub regions of HSV had scattered clusters, with brain regions gathered in the cortex and brainstem, suggesting a bottom-up, leapfrog, multipoint neural sensing pattern of the heart. Both patterns contain many hub brain regions that have been previously overlooked in brain‒heart axis studies. These results provide brain targets for future research and will lead to deeper insight into the brain mechanisms involved in specific heart conditions.
Animals ; Male ; Female ; Heart/physiology* ; Mice ; Herpesvirus 1, Suid ; Brain/physiology* ; Mice, Inbred C57BL ; Brain Mapping ; Efferent Pathways/physiology* ; Afferent Pathways/physiology* ; Simplexvirus ; Sex Characteristics