OBJECTIVE: To investigate the relationship between mean perfusion pressure (MPP) and the risk of sepsis-associated acute kidney injury (SA-AKI) and its prognosis, and to determine the optimal cut-off value of MPP for predicting SA-AKI. METHODS: A retrospective cohort study was conducted. The clinical data of adult patients with sepsis were collected from the Medical Information Mart for Intensive Care-IV 2.2 (MIMIC-IV 2.2) database. The patients were divided into two groups based on the occurrence of SA-AKI. Baseline characteristics, vital signs, comorbidities, laboratory indicators within 24 hours of intensive care unit (ICU) admission, and clinical outcome indicators were collected. Mean MPP was calculated using the average values of mean arterial pressure (MAP) and central venous pressure (CVP), MPP = MAP-CVP. Cox regression models were constructed, relevant confounding factors were adjusted, and multivariate Logistic regression analysis was used to investigate the associations between MPP and the risk of SA-AKI as well as ICU death. The predictive value of MPP for SA-AKI was evaluated using receiver operator characteristic curve (ROC curve) analysis, and the optimal cut-off value was determined. RESULTS: A total of 6 009 patients were ultimately enrolled in the analysis. Among them, SA-AKI occurred in 4 755 patients (79.13%), while 1 254 patients (20.87%) did not develop SA-AKI. Compared with the non-SA-AKI group, the MPP in the SA-AKI group was significantly lowered [mmHg (1 mmHg≈0.133 kPa): 62.00 (57.00, 68.00) vs. 65.00 (60.00, 70.00), P < 0.01], and the ICU mortality was significantly increased [11.82% (562/4 755) vs. 1.59% (20/1 254), P < 0.01]. Three Cox regression models were constructed: model 1 was unadjusted; model 2 was adjusted for gender, age, height, weight and race; model 3 was adjusted for gender, age, height, weight, race, heart rate, respiratory rate, body temperature, hemoglobin, platelet count, white blood cell count, anion gap, HCO₃^-, blood urea nitrogen, serum creatinine, Cl^-, Na⁺, K⁺, fibrinogen, international normalized ratio, blood lactic acid, pH value, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, sequential organ failure assessment score, Charlson comorbidity index score, use of vasopressors, mechanical ventilation, and urine output. Multivariate Logistic regression analysis showed that when MPP was treated as a continuous variable, there was a negative correlation between MPP and the risk of SA-AKI in model 1 and model 2 [model 1: odds ratio (OR) = 0.967, 95% confidence interval (95%CI) was 0.961-0.974, P < 0.001; model 2: OR = 0.981, 95%CI was 0.974-0.988, P < 0.001], and also a negative correlation between MPP and the risk of ICU death (model 1: OR = 0.955, 95%CI was 0.945-0.965, P < 0.001; model 2: OR = 0.956, 95%CI was 0.946-0.966, P < 0.001). However, in model 3, there was no significant correlation between MPP and either SA-AKI risk or ICU death risk. when MPP was used as a multi-categorical variable, in model 1 and model 2, referring to MPP ≤ 58 mmHg, when 59 mmHg ≤ MPP ≤ 68 mmHg, as MPP increased, the risk of SA-AKI progressively decreased (OR value was 0.411-0.638, all P < 0.001), and the risk of ICU death also gradually decreased (OR value was 0.334-0.477, all P < 0.001). ROC curve showed that MPP had a certain predictive value for SA-AKI occurrence [area under the ROC curve (AUC) = 0.598, 95%CI was 0.404-0.746], and the optimal cut-off value was 60.5 mmHg. CONCLUSION MPP was significantly associated with the risk of SA-AKI, with an optimal cut-off value of 60.5 mmHg, and also demonstrated a significant correlation with the risk of ICU death.
Humans ; Acute Kidney Injury/physiopathology* ; Retrospective Studies ; Sepsis/physiopathology* ; Middle Aged ; Prognosis ; Male ; Female ; Aged ; Risk Factors ; Intensive Care Units ; Adult ; Logistic Models ; Proportional Hazards Models

The effective local management of oligometastatic non-small cell lung cancer (NSCLC) has the potential to prolong patients' survival. The role of radiotherapy as a local treatment modality in patients with oligometastatic NSCLC, whether as first-line therapy or consolidation therapy, remains uncertain. Several studies have demonstrated that stereotactic ablative radiotherapy can offer clinical benefits for patients with oligometastatic NSCLC without increasing adverse reactions. Furthermore, the exploration of the potential synergistic effects of combining radiotherapy and immunotherapy on extending progression-free survival and overall survival in patients with oligometastatic NSCLC is also a topic worthy of attention.

Objective To rapidly visualize and detect the extracellular vesicles of glial cells in a simulated space environment.Methods By using 2,5 Gy irradiation and 12,24 h microgravity treatment,a damage model of glial cells was established in a simulated space environment.Exosomes extracted from conditioned media with reagent kits were transferred to neurons to elucidate the impact of glial cells on neurons.By performing live-cell fluorescence labeling of exosomes,a visualization monitoring scheme based on fluorescence intensity analysis was developed to characterize the release patterns of extracellular vesicles.The release patterns of exosomes were represented by the fluorescence intensity of the conditioned media.The effects of different storage conditions and duration on the quantity and size of exosomes were investigated.Results The exosomes released from damaged glial cells in the simulated space environment could to some extent protect neurons,with exosomes playing a decisive role in this process,and the neurosystem exosome visualization detection scheme was consistent with the traditional exosome validation scheme.An empirical curve for exosome quantity and size was established for semi-quantitative analysis,providing a new approach for rapid detection of exosomes in cell culture media.Furthermore,the optimal storage conditions for culture medium samples were clarified,laying the foundation for ground/space-based online analysis of culture medium samples after spaceflight.Conclusion Exosome rapid detection and analysis can be achieved through fluorescence labeling and utilized to investigate glial cell injury in a simulated space environment.

Although chromosomal mosaic embryos detected by trophectoderm(TE)biopsy offer healthy embryos available for transfer,high-resolution postnatal karyotyping and chromosome testing of the transferred embryos are insufficient.Here,we applied single-cell multi-omics sequenc-ing for seven infants with blastula chromosomal mosaicism detected by TE biopsy.The chromo-some ploidy was examined by single-cell genome analysis,with the cellular identity being identified by single-cell transcriptome analysis.A total of 1616 peripheral leukocytes from seven infants with embryonic chromosomal mosaicism and three control ones with euploid TE biopsy were analyzed.A small number of blood cells showed copy number alterations(CNAs)on seem-ingly random locations at a frequency of 0％-2.5％per infant.However,none of the cells showed CNAs that were the same as those of the corresponding TE biopsies.The blastula chromosomal mosaicism may be fully self-corrected,probably through the selective loss of the aneuploid cells dur-ing development,and the transferred embryos can be born as euploid infants without mosaic CNAs corresponding to the TE biopsies.The results provide a new reference for the evaluations of trans-ferring chromosomal mosaic embryos in certain situations.

Objective:To investigate whether radiotherapy should be delivered before the application of immune checkpoint inhibitor PD-1 in patients with advanced non-small cell lung cancer (NSCLC) and evaluate the effect of previous radiotherapy on the efficacy and pulmonary toxicity of PD-1 inhibitor.Methods:Clinical data of patients with stage Ⅳ NSCLC who received immunotherapy in Henan Cancer Hospital from March 2015 to September 2019 were retrospectively analyzed. The baseline data of patients, the status of radiotherapy and immunotherapy and the pulmonary toxicity were collected. According to whether radiotherapy was given before PD-1 inhibitor application, all patients were divided into the previous radiotherapy and non-radiotherapy groups. Survival analysis was performed by Kaplan- Meier method. Results:A total of 90 patients were enrolled including 39 cases in the previous radiotherapy group and 51 cases in the non-radiotherapy group. The median follow-up time was 22.9 months. The median progression-free survival (mPFS) in the previous radiotherapy group was 7.5 months (95% CI 5.4-9.5 months), significantly longer compared with 4.1 months (95% CI 3.1-5.1 months) in the non-radiotherapy group ( P=0.003). The median overall survival (mOS) significantly differed between two groups[15.2 months (95% CI 12.3-18.1 months) vs. 9.3 months (95% CI 6.1-12.5 months)]( P=0.040). The incidence of pulmonary toxicity showed no significant difference between two groups ( P=0.154). Conclusions:Patients with stage Ⅳ NSCLC patients in the previous radiotherapy group obtain significantly better mPFS and mOS and similar pulmonary toxicity compared with their counterparts in the non-radiotherapy group. Nevertheless, the findings remain to be validated by subsequent investigations with larger sample size.

OBJECTIVE：To optimi ze and improve the quality standard for Keqing capsules. METHODS ：According to general rule 0502 method stated in 2015 edition of Chinese Pharmacopeia （part Ⅳ），TLC method was used to identify Reineckia carnea and Morus alba in Keqing capsules [the developing solvents were dichloromethane-ethyl acetate-formic acid （10 ∶ 4 ∶ 0.2，V/V/V） and ethyl acetate-carbinol-ammonia （12 ∶ 2 ∶ 1，V/V/V），respectively]. The contents of morphine and codeine phosphate in Keqing capsules were determined by HPLC. The determination was performed on XBridge C 18 column with mobile phase consisted of acetonitrile-0.01 mol/L potassium dihydrogen phosphate aqueous solution （pH value adjusted to 2.7 with 5％ phosphoric acid solution）（5 ∶ 95，V/V）at the flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm，and the column temperature was 35 ℃. The sample size was 10 µL. RESULTS ：In TLC of R. carnea and M. alba in samples ，same color spots were shown in the correspon ding positions of reference substance chromatogram without interference from negative control. The linear range of morphine and codeine phosphate were batches of Keqing capsules were 0.97-1.37，0.16-0.37 mg/g，respectively. CONCLUSIONS ：TLC identification method for R. carnea and M. alba ，as well as HPLC content determination method for morphine and codeine phosphate in Keqing capsules are established；the method is simple ，accurate and reliable with strong specificity ，which improves the quality standard of Keqing capsules.

Gastrodin is a phenolic glycoside that has been demonstrated to provide neuroprotection in preclinical models of central nervous system disease, but its effect in subarachnoid hemorrhage (SAH) remains unclear. In this study, we showed that intraperitoneal administration of gastrodin (100 mg/kg per day) significantly attenuated the SAH-induced neurological deficit, brain edema, and increased blood-brain barrier permeability in rats. Meanwhile, gastrodin treatment significantly reduced the SAH-induced elevation of glutamate concentration in the cerebrospinal fluid and the intracellular Ca overload. Moreover, gastrodin suppressed the SAH-induced microglial activation, astrocyte activation, and neuronal apoptosis. Mechanistically, gastrodin significantly reduced the oxidative stress and inflammatory response, up-regulated the expression of nuclear factor erythroid 2-related factor 2, heme oxygenase-1, phospho-Akt and B-cell lymphoma 2, and down-regulated the expression of BCL2-associated X protein and cleaved caspase-3. Our results suggested that the administration of gastrodin provides neuroprotection against early brain injury after experimental SAH.
Animals ; Apoptosis ; drug effects ; Astrocytes ; drug effects ; metabolism ; Benzyl Alcohols ; administration & dosage ; Blood-Brain Barrier ; drug effects ; metabolism ; Brain ; drug effects ; metabolism ; Brain Edema ; etiology ; prevention & control ; Calcium ; metabolism ; Glucosides ; administration & dosage ; Glutamic Acid ; metabolism ; Male ; Microglia ; drug effects ; metabolism ; Neurons ; drug effects ; Neuroprotective Agents ; administration & dosage ; Oxidative Stress ; drug effects ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; complications ; metabolism ; prevention & control

Objective To compare the effects of different extracts of Rheum palmatum on weight and tissue structure of hypothalamusand and pituitary of adult female rats,and screen the main reproductive toxicity extract.Methods The water,chloroform,ethyl acetate,and n-butanol extracts and water-soluble substance of R.palmatum were prepared by polarity gradient extraction method.Female adult rats were randomly divided into blank control group,rhubarb water extract group,and different extracts groups.The dosage of all the groups was equivalent to 4.00 g/kg crude rhubarb.Rats were administered with extracts by gavage for 60 d.Body mass growth rate of rats were calculated before and after administration.The pathological changes of hypothalamic arcuate nucleus neurons and pituitary gonadal cell were observed with light microscope.Results Compared with the blank control group,the body mass growth rate of rhubarb water extract group was decreased (P ＜ 0.05),while those in the different extracts groups were increased (P ＜ 0.01);The hypothalamic arcuate nucleus neurons of rhubarb water extract group showed chromatin marginalization,nissl substance dissolving,fuzzy boundary of nuclear membrane,as well as hell cells,and the total number of adenohypophysis cells reduced and the cells arranged in irregular.However,there were no apparent pathologic changes in different extracts groups.Conclusion Rhubarb water extract administration by long-term dose can reduce weight growth rate and result in pathologic changes of hypothalamic arcuate nucleus and adenohypophysis,while the different extracts can increase weight growth rate significantly and have little effects on the organizational structure ofhypothalamic arcuate nucleus and adenohypophysis.

Objective To investigate the relationship between cytochrome P450 1A2 (CYP1A2) gene polymorphism and susceptibility to chronic obstructive pulmonary disease (COPD). Methods CYP1A2 gene polymorphisms in 100 COPD cases and 100 healthy controls were tested with polymerase chain reaction- restriction fragment length polymorphism (PCR- RELP). Results Genotype frequencies of 4 SNPs in both the COPD and control groups were in accordance with Hardy-Weinberg equilibrium (P>0.05). There was significant difference between the COPD and control groups in genotype and allele frequencies of 1D and 1F (P<0.05), but not of 1C and 1E (P>0.05). Conclusion CYP1A2*1D and CYP1A2*1F polymorphisms may play an important role in the development of COPD.