OBJECTIVES: To investigate the association of serum albumin level after human albumin infusion with 28-day mortality in critically ill patients with acute kidney injury (AKI) and its impact on 90-day outcomes of the patients. METHODS: We conducted a retrospective cohort study based on the MIMIC IV database (2008-2019), including 5918 AKI patients treated with albumin in the ICU. Based on serum albumin levels within 72 h after albumin infusion, the patients were divided into low (<30 g/L), medium (30-35 g/L), and high albumin (>35 g/L) groups. Restricted cubic spline regression and multivariate logistic regression were used to analyze the association of albumin levels with patient mortality, and the results were verified in a external validation cohort consisting of 110 sepsis-induced AKI patients treated in Nanfang Hospital between 2017 and 2022 using survival analysis and multivariate adjustment. RESULTS: In the MIMIC training cohort, multivariate logistic regression showed no significant differences in 28-day mortality of the patients with different albumin levels (P>0.05). However, restricted cubic spline analysis indicated a non-linear dose-response relationship between albumin levels and 28-day mortality (threshold effect: risk increased when albumin levels >3.6 g/dL). Secondary endpoint analysis revealed that the patients with high albumin levels had a shorter duration of mechanical ventilation (P<0.001) but a longer ICU stay (P<0.001). In the validation cohort, albumin levels ≥30 g/L were significantly associated with a reduced 28-day mortality rate (P<0.05). CONCLUSIONS The association between increased serum albumin levels following albumin infusion and 28-day mortality of critically ill patients with AKI exhibits a cohort dependency and can be influenced by multiple factors including disease type and severity, infusion strategies, and statistical methods.
Humans ; Acute Kidney Injury/therapy* ; Critical Illness/mortality* ; Retrospective Studies ; Serum Albumin/analysis* ; Male ; Female ; Intensive Care Units ; Middle Aged ; Logistic Models ; Aged

Objective:To investigate the clinicopathological features, immunophenotype, molecular characteristics, and differential diagnosis of MED15-TFE3 gene fusion renal cell carcinoma (MED15-TFE3 RCC).Methods:A total of 12 MED15-TFE3 RCCs, diagnosed from 2016 to 2023, were collected from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China for clinicopathologic, immunohistochemical, fluorescence in situ hybridization (FISH) and RNA sequencing (RNA-seq) analyses and follow-up. In addition, its diagnosis and differential diagnosis were also explored.Results:There were five males and seven females. The patients′ ages ranged from 16 to 60 years, with an average age of 40.4 years. The follow-up time ranged from 15 to 92 months, and no recurrence or metastasis was observed. Histologically, 6 cases exhibited extensive cystic structures with almost no solid sheet components, while the remaining 6 cases displayed a cysto-solid growth pattern. The cytoplasm of the tumor cells appeared flocculent, with a clear or faintly eosinophilic appearance, and nucleoli were inconspicuous. Psammoma bodies were observed in 12 cases. There was deposition of basement membrane-like material in 5 cases. All cases showed strong expression of TFE3, GPNMB, Cathepsin K, Melan A, and PAX8, while no expression of CAⅨ or CK7. FISH analyses showed that all 12 cases were positive for the MED15-TFE3 fusion, while the MED15-TFE3 fusion gene and specific fusion sites were detected in 2 cases using RNA-seq.Conclusions:MED15-TFE3 RCC is a type of TFE3-rearranged renal cell carcinoma that exhibits both identifiable diagnostic characteristics and highly deceptive morphology. Its distinct extensive cystic structure can be easily confused with multilocular cystic renal neoplasm of low malignant potential, necessitating careful differentiation in routine practice.

[Objective] To evaluate the clinical application value of intrauterine perfusion with platelet-rich plasma (PRP) combined with in vitro fertilization-frozen-thawed embryo transfer (IVF-FET) in patients with chronic endometritis (CE). [Methods] A randomized controlled trial (RCT) was conducted, enrolling 60 CE patients undergoing artificial cycle frozen embryo transfer at our hospital from January 2022 to January 2024. Participants were randomly divided into three groups: Group A (routine frozen embryo transfer, n=20), Group B (routine frozen embryo transfer + one PRP intrauterine perfusion, n=20), and Group C (routine frozen embryo transfer + two PRP intrauterine perfusions, n=20). Endometrial thickness during the transformation and transplantation phases, uterine artery pulsatility index (PI), resistance index (RI), systolic peak velocity/end-diastolic velocity (S/D) ratio during transplantation, serum levels of IL-2, IL-4, IL-6, IL-10, and TNF-α during transplantation, as well as biochemical pregnancy rate, clinical pregnancy rate, live birth rate, and early miscarriage rate were compared across groups. [Results] No significant differences in endometrial thickness were observed among the three groups during the transformation phase (P>0.05). During the transplantation phase, endometrial thickness in Groups C and B was significantly higher than in Group A[9.54 (8.96-10.22) and 8.90 (8.34-9.72) vs 8.37 (7.89-8.75) mm, P<0.05], with Group C showing greater thickness than Group B (Z=3.733, P<0.05). Endometrial thickness in Groups C and B during transplantation was significantly increased compared to their respective transformation phases (Z=2.191, 2.462; P<0.05). Groups C and B exhibited lower PI, RI, and S/D values than Group A[PI:1.87 (1.77-1.97), 1.94 (1.88-2.15) vs 2.43 (2.35-2.49); RI:0.75 (0.73-0.77), 0.78 (0.75-0.81) vs 0.84 (0.83-0.86); S/D:2.61 (2.33-3.42), 3.01 (2.20-3.93) vs 3.72 (3.06-4.49); P<0.05]. Group C demonstrated lower PI and RI than Group B (P<0.05). IL-2 levels in Groups C and B were higher than in Group A[3.88 (2.71-5.01), 3.59 (2.73-4.38) vs 3.16 (2.11-3.25) ng/L, P<0.05], while IL-4, IL-6, IL-10, and TNF-α levels were significantly lower (IL-4: Z=1.428, 2.421; IL-6: Z=1.754, 2.435; IL-10: Z=1.754, 2.854; TNF-α: Z=1.961, 1.765; P<0.05). Group C had lower IL-6 levels than Group B (Z=3.976, P<0.05). Biochemical pregnancy rate, clinical pregnancy rate, and live birth rate in Group C were significantly higher than in Group A (75% vs 40%, 70% vs 35%, 60% vs 20%, P<0.05). No significant differences in early miscarriage rates were observed among the groups (χ²=3.750, P>0.05). [Conclusion] Intrauterine autologous PRP perfusion in CE patients enhances pregnancy and live birth rates, improves pregnancy outcomes post-FET, and demonstrates superior efficacy in endometrial repair and receptivity with two PRP perfusions compared to a single perfusion. This provides a safe and effective therapeutic option for optimizing outcomes in CE patients with prior implantation failure.

Objective:To investigate the clinicopathological features, immunophenotype, molecular characteristics, and differential diagnosis of MED15-TFE3 gene fusion renal cell carcinoma (MED15-TFE3 RCC).Methods:A total of 12 MED15-TFE3 RCCs, diagnosed from 2016 to 2023, were collected from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China for clinicopathologic, immunohistochemical, fluorescence in situ hybridization (FISH) and RNA sequencing (RNA-seq) analyses and follow-up. In addition, its diagnosis and differential diagnosis were also explored.Results:There were five males and seven females. The patients′ ages ranged from 16 to 60 years, with an average age of 40.4 years. The follow-up time ranged from 15 to 92 months, and no recurrence or metastasis was observed. Histologically, 6 cases exhibited extensive cystic structures with almost no solid sheet components, while the remaining 6 cases displayed a cysto-solid growth pattern. The cytoplasm of the tumor cells appeared flocculent, with a clear or faintly eosinophilic appearance, and nucleoli were inconspicuous. Psammoma bodies were observed in 12 cases. There was deposition of basement membrane-like material in 5 cases. All cases showed strong expression of TFE3, GPNMB, Cathepsin K, Melan A, and PAX8, while no expression of CAⅨ or CK7. FISH analyses showed that all 12 cases were positive for the MED15-TFE3 fusion, while the MED15-TFE3 fusion gene and specific fusion sites were detected in 2 cases using RNA-seq.Conclusions:MED15-TFE3 RCC is a type of TFE3-rearranged renal cell carcinoma that exhibits both identifiable diagnostic characteristics and highly deceptive morphology. Its distinct extensive cystic structure can be easily confused with multilocular cystic renal neoplasm of low malignant potential, necessitating careful differentiation in routine practice.

Objective:To observe whether endothelial cells undergo pyroptosis in the inflammatory periodontal environment by using a model in vivo and in vitro, providing an experimental basis for indepth understanding of the underlying pathogenesis of periodontitis. Methods:According to the classification of periodontal diseases of 2018, gingival tissues were collected from periodontally healthy subjects and patients with stage Ⅲ-Ⅳ, grade C periodontitis, who presented Department of Oral and Maxillofacial Surgery and Department of Periodontology, School of Stomatology, The Fourth Military Medical University from April to May 2022. Immunohistochemical staining was performed to detect the expression level and distribution of gasdermin D (GSDMD), a hallmark protein of cell pyroptosis, in gingival tissues. Periodontitis models were established in each group by ligating the maxillary second molar teeth of three mice for 2 weeks (ligation group). The alveolar bone resorption was determined by micro-CT (mice without ligation treatment were used as the control group), and the colocalization of GSDMD and CD31 were quantitatively analyzed by immunofluorescence staining in gingival tissues of healthy and inflammatory mice. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and treated with lipopolysaccharide (LPS) of Porphyromonas gingivalis (Pg) combined with adenosine triphosphate (ATP) at various concentrations of 0.5, 1.0, 2.5, 5.0, and 10.0 mg/L, respectively, and the 0 mg/L group was set as the control group at the same time. Scanning electron microscopy was used to observe the morphology of HUVECs. Western blotting was used to detect the expression of gasdermin D-N terminal domains (GSDMD-N) protein and immunofluorescence cell staining was used to detect the expression and distribution of GSDMD. Cell counting kit-8 (CCK-8) was used to detect the proliferative ability of HUVECs, and propidium iodide (PI) staining was used to detect the integrity of cell membrane of HUVECs. Results:Immunohistochemistry showed that GSDMD in gingival tissues of periodontitis was mainly distributed around blood vessels and its expression level was higher than that in healthy tissues. Micro-CT showed that alveolar bone resorption around the maxillary second molar significantly increased in ligation group mice compared with control subjects ( t=8.88, P<0.001). Immunofluorescence staining showed significant colocalization of GSDMD with CD31 in the gingival vascular endothelial cells in mice of ligation group. The results of scanning electron microscopy showed that there were pores of different sizes, the typical morphology of pyroptosis, on HUVECs cell membranes in the inflammatory environment simulated by ATP combined with different concentrations of LPS, and 2.5 mg/L group showed the most dilated and fused pores on cell membranes, with the cells tended to lyse and die. Western blotting showed that the expression of GSDMD-N, the hallmark protein of cell pyroptosis, was significantly higher in 2.5 and 5.0 mg/L groups than that in the control group ( F=3.86, P<0.01). Immunofluorescence cell staining showed that the average fluorescence intensity of GSDMD in 2.5 mg/L group elevated the most significantly in comparison with that in the control group ( F=35.25, P<0.001). The CCK-8 proliferation assay showed that compared to the control group (1.00±0.02), 0.5 mg/L (0.52±0.07), 1.0 mg/L (0.57±0.10), 2.5 mg/L (0.58±0.04), 5.0 mg/L (0.55±0.04), 10.0 mg/L (0.61±0.03) groups inhibited cell proliferation ( F=39.95, P<0.001). PI staining showed that the proportion of positive stained cells was highest [(56.07±3.22)%] in 2.5 mg/L group ( F=88.24, P<0.001). Conclusions:Endothelial cells undergo significant pyroptosis in both in vivo and in vitro periodontal inflammatory environments, suggesting that endothelial cell pyroptosis may be an important pathogenic factor contributing to the pathogenesis of periodontitis.

Objective To explore the differences in brain functions between individuals with good acclimatization to high altitudes and those with poor acclimatization based on microstate and functional connectivity analysis of resting-state electroencephalogram(EEG)activities.Methods A total of 44 residents exposed to the high-altitude environment of 3 650 m above sea level were enrolled.They were divided into two groups according to their findings for the high-altitude acclimatization index(AAI),with 22 in the good acclimatization group and 22 in the poor acclimatization group.The good acclimatization group had 10 males and 12 females of the mean age of(20.48±2.09)years.Among them,10 were Tibetans,and 12 were Han Chinese.The poor acclimatization group consisted of 18 males and 4 females,with a mean age of(18.90±1.25)years.Among them,7 were Tibetans,and 15 were Han Chinese.The K-means clustering algorithm was used to classify EEG microstates into four categories of A,B,C,and D.The average duration,coverage,occurrence frequency,and transition probabilities between microstates were compared.Coherence analysis(COH)was performed to assess the strength of brain network connectivity.Results Compared to the good acclimatization group,the poor acclimatization group exhibited a longer duration,higher occurrence frequency,and coverage of microstate C.The coverage of microstate D was also higher,while the occurrence frequency and coverage of microstate B were lower.The poor acclimatization group showed a decrease in transitions from microstate B to A or D,while transitions from C to B or D,and those from D to A or C increased,showing statistically significant differences between the groups(P＜0.05).In the α,β,δ,and θ frequency bands,the poor acclimatization group had higher COH strength in regions such as the frontal and occipital lobes,showing symmetrical functional connectivity between the left and right hemispheres.Conclusion The good and poor high-altitude acclimatization groups exhibit different neural mechanisms in terms of microstates and functional connectivity.There are significant differences between individuals with good acclimatization and those with poor acclimatization regarding visual information processing,interference resistance,brain network stability,and coherence.

Objective:To review and summarize the main problems that have occurred in the history of manned spaceflight worldwide and the experience of the medical rescue support for astronauts at the main landing site since the first manned spaceflight mission of the Shenzhou-5 in China in 2003, focus on the technical status and return characteristics during the construction of the space station since the Shenzhou-12, and formulate a targeted injury treatment plan to ensure the safety of astronauts.Methods:This article summarized the lessons of accidental injuries of astronauts in foreign aerospace history, especially in the space station stage, combined with the experience of medical support of astronauts in manned spaceflight in China, and put forward a series of organizations, plans and treatments according to the mission characteristics of long-term orbits and adjustments of the main landing sites of space station mission spacecraft.Results:On the basis of the original pre-cabin emergency and helicopter ICU comprehensive rescue platform, the emergency procedures were further optimized, and the treatment plans under different complex terrains and the principles of rapid treatment and evacuation of astronauts were formulated.Conclusions:The effective treatment of astronauts returning from the space station in various situations could be ensured by the comprehensive rescue plan for the medical rescue of the space station mission and the construction and organization of the helicopter rescue platform.

Objective:This study aims to analyze the characteristics and basic principles of emergency surgery risks and anesthesia care of medical support at the landing site for China’s taikonauts of the Shenzhou-12, and to summarize China’s experience in medical support at the landing site for manned spaceflight, and ensure supports in special environments such as an emergency return of manned spaceflight.Methods:This study was carried out through literature research on relevant reports on the emergency surgery risks and aids of domestic and foreign astronauts at the landing sites, and summaries of the experience in medical support for taikonauts of spacecrafts from Shenzhou-5 to Shenzhou-11 at the landing sites. At the same time, according to the characteristics of Shenzhou-12 such as the long on-orbit time, the adjustment in the landing area, the optimization of the mission mode, and new search and rescue power, a series of organization, pre-arranged planning, equipment allocation, and effective anesthesia treatment plan were proposed and inspected in practice.Results:Based on the original anesthesia care plan of medical support, the first-aid carrier was adjusted and modified, the first-aid procedure was optimized, a new generation of supraglottic airway opening tool, video laryngoscope, portable ultrasound, and other devices were added, and the anesthesia care plan at the landing site for manned spaceflight was formulated to provide strong support for the medical care of taikonauts that had stayed in the outer space for a long time.Conclusions:Upon the targeted improvement and process optimization, the anesthesia care plan of medical support for taikonauts of Shenzhen-12 in the landing area fully meets the anesthesia requirement of medical support in special environments such as the emergency return of the taikonauts that have stayed in the outer space for a long time under the new orbital altitude.

To analyze how the handover were effected by the conditions of manned spaceflight medical support mission through the practice of medical equipment and drugs in Shenzhou-12 and Shenzhou-13 manned spaceflight medical rescue support missions, this article discussed the preparation, organization and implementation in the handover of medical equipment and drugs in the changing of medical rescue teams, summarized the notices in the work of handover, and provided experience for the smooth handover of different manned spaceflight medical rescue teams in the future.

Objective:To study the effects of trioxygen pretreatment on cerebral ischemia/reperfusion (I/R) injury in rats.Methods:A total of 24 clean grade male Sprague-Dawley (SD) rats were randomly divided into Sham group, brain I/R group (I/R group) and Ozone pretreatment group (Ozone group), with 8 rats in each group. The animals were routinely fed, and the operation was performed 5 days after the intervention of Ozone group by intraperitoneal injection of trioxygen water (concentration 80 mg/L, 0.01 mL/g), and the Sham group and I/R group were injected with equal volume normal saline. The Sham group only separated the arteries without ligation, and the I/R group and Ozone group established the rat cerebral I/R model. Neurological deficit score (NDS) was performed 2 hours after ischemia and modified neurological deficit score (mNSS) was performed 24 hours after reperfusion. Brain tissue was collected after anesthesia. Cerebral infarction was observed by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining and the percentage of cerebral infarction volume was calculated. Protein expression of metabolic glutamate receptor 5 (mGluR5) and ionic glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluA2 in cerebral ischemic penumbra was determined by Western blotting.Results:Compared with the Sham group, NDS score, mNSS score and percentage of cerebral infarction volume in I/R group were increased [NDS score: 2.63±0.52 vs. 0, mNSS score: 9.63±1.19 vs. 1.13±0.64, cerebral infarction volume: (41.25±2.93)% vs. 0%, all P < 0.05], and expressions of mGluR5 and GluA2 in penumbra area of cerebral ischemia were decreased [mGluR5 protein (mGluR5/β-actin): 0.44±0.14 vs. 1.00±0.10, GluA2 protein (GluA2/β-actin): 0.23±0.08 vs. 1.00±0.25, both P < 0.05]. Compared with the I/R group, mNSS score and percentage of cerebral infarction volume in the Ozone group were decreased [mNSS score: 7.00±1.20 vs. 9.63±1.19, cerebral infarction volume: (27.23±6.21)% vs. (41.25±2.93)%, both P < 0.05], and mGluR5 and GluA2 expressions in the penumbra of cerebral ischemia were up-regulated [mGluR5 protein (mGluR5/β-actin): 0.81±0.10 vs. 0.44±0.14, GluA2 protein (GluA2/β-actin): 0.76±0.13 vs. 0.23±0.08, both P < 0.05]. Conclusion:Trioxygen preconditioning can alleviate cerebral I/R injury in rats, and its mechanism may be related to the upregulation of GluR5 and GluA2 in the ischemic penumbra.