OBJECTIVE: To develop a method for identifying high-risk patients among septic populations requiring mechanical ventilation, and to conduct phenotypic analysis based on this method. METHODS: Data from four sources were utilized: the Medical Information Mart for Intensive Care (MIMIC-IV 2.0, MIMIC-III 1.4), the Philips eICU-Collaborative Research Database 2.0 (eICU-CRD 2.0), and the Anhui Medical University Second Affiliated Hospital dataset. The adult patients in intensive care unit (ICU) who met Sepsis-3 and received invasive mechanical ventilation (IMV) on the first day of first admission were enrolled. The MIMIC-IV dataset with the highest data integrity was divided into a training set and a test set at a 6:1 ratio, while the remaining datasets were served as validation sets. The demographic information, comorbidities, laboratory indicators, commonly used ICU scores, and treatment measures of patients were extracted. Clinical data collected within first day of ICU admission were used to calculate the sequential organ failure assessment (SOFA) score. K-means clustering was applied to cluster SOFA score components, and the sum of squared errors (SSE) and Davies-Bouldin index (DBI) were used to determine the optimal number of disease subtypes. For clustering results, normalized methods were employed to compare baseline characteristics by visualization, and Kaplan-Meier curves were used to analyze clinical outcomes across phenotypes. RESULTS: This study enrolled patients from MIMIC-IV dataset (n = 11 166), MIMIC-III dataset (n = 4 821), eICU-CRD dataset (n = 6 624), and a local dataset (n = 110), with the four datasets showing similar median ages and male proportions exceeding 50%; using 85% of the MIMIC-IV dataset as the training set, 15% as the test set, and the rest dataset as the validation set. K-means clustering based on the six-item SOFA score was performed to determine the optimal number of clusters as 3, and patients were finally classified into three phenotypes. In the training set, compared with the patients with phenotype II and phenotype III, those with phenotype I had the more severe circulatory and respiratory dysfunction, a higher proportion of vasoactive drug usage, more obvious metabolic acidosis and hypoxia, and a higher incidence of congestive heart failure. The patients with phenotype II was dominated by respiratory dysfunction with higher visceral injury. The patients with phenotype III had relatively stable organ function. The above characteristics were consistent in both the test and validation sets. Analysis of infection-related indicators showed that the patients with phenotype I had the highest SOFA score within 7 days after ICU admission, initial decreases and later increases in platelet count (PLT), and higher counts of neutrophils, lymphocytes, and monocytes as compared with those with phenotype II and phenotype III, their blood cultures had a higher positivity rates for Gram-positive bacteria, Gram-negative bacteria and fungi as compared with those with phenotype II and phenotype III. The Kaplan-Meier curve indicated that in the training, test, and validation sets, the 28-day cumulative mortality of patients with phenotype I was significantly higher than that of patients with phenotypes II and phenotype III. CONCLUSIONS Three distinct phenotypes in septic patients receiving IMV based on unsupervised machine learning is derived, among which phenotype I, characterized by cardiorespiratory failure, can be used for the early identification of high-risk patients in this population. Moreover, this population is more prone to bloodstream infections, posing a high risk and having a poor prognosis.
Humans ; Machine Learning ; Sepsis/therapy* ; Respiration, Artificial ; Intensive Care Units ; Organ Dysfunction Scores ; Male ; Female ; Middle Aged ; Adult

Recurrent spontaneous abortion(RSA)has complex etiologies,including embryonic chromosomal abnormalities,maternal immune factors,prethrombotic states,and uterine anatomical a-nomalies.Currently,the pathogenesis of RSA remains incompletely elucidated,with placental tropho-blast dysfunction considered a key factor contributing to pregnancy failure.Recent studies have dem-onstrated that non-coding RNA(ncRNA)are stably expressed at the maternal-fetal interface and reg-ulate the proliferation,apoptosis,invasion,and metastasis of trophoblast immune cells.The ncRNA can directly modulate target gene expression or influence the occurrence and progression of RSA through competitive endogenous RNA(ceRNA)regulatory networks,providing novel targets for re-searchers exploring the pathogenesis of RSA.Additionally,ncRNA mediate intercellular interactions via vesicular transport,offering new insights into their regulatory mechanisms.Due to their tissue spe-cificity and expression stability,ncRNA are promising as novel biomarkers for RSA and other preg-nancy-related disorders.This review summarized the regulatory roles of ncRNA in the immune mecha-nisms underlying the occurrence and development of RSA based on multiple domestic and internation-al studies.

Objective:To investigate the carriage of the thalassemia gene in sperm donors in Chongqing,China by analyzing the thalas-semia screening and gene mutation types of sperm donors in Chongqing Human Sperm Bank(CHSB),and to provide a reference for thalassemia screening in sperm donors in Chongqing.Methods:Blood samples were collected from 488 sperm donors in CHSB(donors with all tests qualified during the quarantine)from December 2021 to August 2024.A complete blood count analysis was performed to measure the mean corpuscular volume(MCV)and mean corpuscular hemoglobin(MCH).Polymerase chain reaction(PCR)/agarose gel electrophoresis was used to detect deletional α-thalassemia mutations.PCR and DNA reverse dot blot hybridization were used to detect 3 common non-deletional α-thalassemia mutations and 17 common β-thalassemia mutations.The test results were then analyzed.Results:Among the 488 sperm donors aged 25.64±4.95 years,15(3.07％,all Han nationality)tested positive for thalassemia.This carriage rate was lower than that of the thalassemia population in Chongqing(9.24％).Among the 15 thalassemia carriers,13 had deletional α-gene mutations(-α3.7 genotype in 11 cases[73.33％],-α4.2 genotype in 1 case[6.67％],and-SEA genotype in 1 case[6.67％]),and 2 had non-deletional α-gene mutations(both with the WSM heterozygous mutation).There was only 1 case of abnor-mal MCV and MCH2 indicators among thalassemia carriers(screening positive rate was 6.67％).Conclusion:Thalassemia screening in sperm donors in CHSB reveals a low thalassemia carriage rate,reflecting geographic(predominantly Sichuan and Chongqing ori-gins)and demographic(healthy men of childbearing potential)characteristics.Given the significant impact of thalassemia on the off-spring conceived through sperm donation,it is recommended to conduct thalassemia gene screening among sperm donors in human sperm banks.

Objective: To assess the association between Life eight ( LE8) scores and diabetes mellitus ( DM) ， and to examine the mediating effect of Methylmalonic acid (MMA). Methods: Based on cross-sectional data from the 2011—2014 National Health and Nutrition Examination Survey (NHANES) ，weighted multivariable logistic regression analyses were conducted to assess the association between the LE8 score and DM．A mediation model was further constructed to evaluate the mediating effect of MMA． Results: The weighted multivariable logistic regression analysis showed a significant negative correlation between LE8 score and the risk of DM．After adjusting for poten- tial confounders，a 1-point increase in LE8 was associated with a 7% reduction in DM risk ( OR = 0. 93，95% CI: 0. 92－0. 93，P = 0. 000 1) ．In contrast，the level of circulating MMA did not show a statistically significant rela- tionship with DM risk ( OR = 0. 99，95% CI: 0. 89 －1. 10，P = 0. 886 8) ．Further subgroup analysis by age re- vealed that in participants under 60 years of age，circulating MMA levels were positively associated with DM risk ( OR = 1. 39，95% CI: 1. 19 －1. 62 ，P ＜0. 000 1 ) ． Mediation analysis indicated that circulating MMA levels played a partial mediating role in the relationship between LE8 and DM，with a mediation ratio of 1. 5% (P < 0. 000 1) ． Conclusion High LE8 scores significantly reduce the risk of DM ，and circulating MMA levels may play a role in this，particularly among individuals younger than 60 years (individuals＜60 years of age

Objective:To evaluate the effect of individualized positive end-expiratory pressure (PEEP) titration based on open-lung strategy on the intraoperative thoracic fluid content (TFC) in elderly patients undergoing transurethral ultrasound-guided laser-induced prostatectomy (TULIP).Methods:Eighty-six American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, patients, aged 65-80 yr, with body mass index of 18-28 kg/m 2, scheduled for elective TULIP, were divided into 2 groups ( n=43 each) by the random number table method: fixed PEEP group (group C) and individualized PEEP titration group (group P). PEEP was set at 4 cmH 2O after routine mechanical ventilation in group C. Patients underwent pulmonary recruitment maneuvers combined with individualized PEEP titration during surgery in group P. TFC was measured using a non-invasive cardiac output monitor at 5 min after tracheal intubation (T 0), 30 min after PEEP titration and ventilation (T 1), 5 min before surgery (T 2), and 5 min before leaving the recovery room (T 3). Cardiac output, oxygenation index and stroke volume index were recorded from T 0-T 2, arterial blood gas analysis was simultaneously performed to record peak airway pressure and dynamic lung compliance, and oxygenation index was calculated. The duration of postanesthesia care unit stay, pulmonary complications within 7 days after surgery, and length of hospital stay were also recorded. Results:Eighty-three patients were finally included, with 42 in group C and 41 in group P. Compared with group C, TFC was significantly decreased at T 1-T 3, cardiac index, cardiac output and stroke volume index were decreased at T 1, dynamic lung compliance, PaO 2 and oxygenation index were increased at T 1 and T 2, PaCO 2 was decreased, the incidence of postoperative pulmonary complications was reduced, and the duration of postanesthesia care unit stay and postoperative length of hospital stay were shortened in group P ( P<0.05). Conclusions:Individualized PEEP titration based on open-lung strategy can effectively decrease TFC and improve intraoperative oxygenation and prognosis in elderly patients undergoing TULIP.

Objective:To evaluate the effect of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) on regional cerebral oxygen saturation (rScO 2) during induction of general anesthesia in patients undergoing traumatic brain injury (TBI) emergency surgery. Methods:A prospective randomized controlled trial was conducted. The TBI emergency general anesthesia patients who underwent intracranial hematoma removal surgery at the Northern Jiangsu People's Hospital from January to July in 2023 were enrolled. The patients were divided into a conventional mask ventilation group and a THRIVE group using a random number table method. The patients in the conventional mask ventilation group were anesthetized and induced to pre oxygenate without positive pressure ventilation in the front mask for 10 minutes, with an oxygen flow rate of 8 L/min and an fraction of inspired oxygen (FiO 2) of 1.00. After anesthesia induction for about 90 s, tracheal intubation was performed after the muscle relaxant took effect (patient's jaw muscle was relaxed). The patients in the THRIVE group were pre oxygenated with THRIVE for 10 minutes, with an oxygen flow rate of 30 L/min and a FiO 2 of 1.00. During anesthesia induction, the oxygen flow rate was increased to 50 L/min, and anesthesia induction medication was used. The lower jaw of patient was supported with both hands to maintain airway patency, and the patient's mouth was kept closed throughout the process. After the muscle relaxant took effect (the patient's jaw muscle was relaxed), tracheal intubation was performed. At the time of patient entering the operating room, 10 minutes of pre oxygenation, and immediately after successful intubation, rScO 2 was measured on the surgical and non-surgical sides. At the same time, ultrasound was used to measure the cross-sectional area (CSA) of the gastric antrum and arterial blood gas analysis was performed. The partial pressure of end-tidal carbon dioxide (P ETCO 2) during the first mechanical ventilation after successful tracheal intubation, the incidence of hypoxemia [pulse oxygen saturation (SpO 2) < 0.95] during tracheal intubation, as well as prognostic indicators such as the length of intensive care unit (ICU) stay, total length of hospital stay, and Glasgow outcome scale (GOS) score at discharge were recorded. Results:During the study period, a total of 70 TBI patients underwent emergency general anesthesia surgery, of which 2 patients died postoperatively, 2 patients were unable to cooperate with closed mouth breathing, and 3 patients had poor ultrasound image acquisition in the gastric antrum, all of whom were excluded. A total of 63 patients were ultimately enrolled, including 32 in the conventional mask ventilation group and 31 in the THRIVE group. There were no statistically significant differences in gender, age, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, Glasgow coma scale (GCS) score, optic nerve sheath diameter (ONSD), baseline vital signs, fasting situation, anesthesia time, surgical time, and intraoperative blood loss between the patients in the two groups, indicating comparability. When entering the operating room, there was no statistically significant difference in rScO 2 on the surgical and non-surgical sides, and blood gas analysis indexes arterial partial pressure of oxygen (PaO 2) and arterial partial pressure of carbon dioxide (PaCO 2) between the patients in the two groups. When pre oxygenated for 10 minutes, both the surgical and non-surgical sides rScO 2 levels in the THRIVE group were significantly higher than those in the conventional mask ventilation group (surgical side: 0.709±0.036 vs. 0.636±0.028, non-surgical side: 0.791±0.016 vs. 0.712±0.027, both P < 0.01), and the PaO 2 was significantly increased [mmHg (1 mmHg≈0.133 kPa): 450.23±60.99 vs. 264.88±49.33, P < 0.01], PaCO 2 was significantly reduced (mmHg: 37.81±3.65 vs. 43.59±3.76, P < 0.01), and the advantage continues tilled immediately after successful intubation. There was no statistically significant difference in CSA at each time point of ultrasound examination between the two groups. Compared with the conventional mask ventilation group, the patients in the THRIVE group showed a significant decrease in P ETCO 2 during the first mechanical ventilation after successful tracheal intubation (mmHg: 43.10±2.66 vs. 49.22±3.31, P < 0.01), and the incidence of hypoxemia during tracheal intubation was also significantly reduced [0% (0/31) vs. 28.12% (9/32), P < 0.01]. In terms of prognostic indicators, there was no statistically significant difference in the length of ICU stay and total length of hospital stay between the patients in the conventional mask ventilation group and the THRIVE group [length of ICU stay (days): 10 (9, 10) vs. 10 (9, 11), total length of hospital stay (days): 28.00 (26.00, 28.75) vs. 28.00 (27.00, 29.00), both P > 0.05]. However, the proportion of patients in the THRIVE group with a good prognosis at discharge (GOS score > 3) was significantly higher than that in the conventional mask ventilation group [35.5% (11/31) vs. 12.5% (4/32), P < 0.05]. Conclusion:THRIVE can significantly increase rScO 2 during anesthesia induction in TBI emergency surgery patients and improve their neurological function prognosis.

Objective:To evaluate the accuracy of inferior vena cava (IVC) parameters measured by ultrasound in predicting post-induction hypotension(PIH) in patients undergoing general anesthesia using a meta-analysis.Methods:Databases such as China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, PubMed, Cochrane Library and Embase were searched for diagnostic clinical trials that involved IVC parameters such as IVC collapsibility index (IVCCI), maximum and minimum IVC diameters (dIVCmax, dIVCmin) measured by ultrasound that predicted PIH from inception to May 2022. Primary outcomes were sensitivity, specificity, and the area under the receiver operating characteristic curve of each parameter. The meta regression analysis and subgroup analysis were used to explore the sources of heterogeneity.Results:Nineteen articles were ultimately included ( n=1 750). The sensitivity and specificity of IVCCI in predicting PIH were 0.73 and 0.82 respectively, and the area under the summary receiver operating characteristic curve(AUSROC) was 0.85, and the prediction threshold of IVCCI was (42.5±6.8)%. The sensitivity and specificity of dIVCmax in predicting PIH were 0.46 and 0.74 respectively, and the AUSROC was 0.64. The sensitivity and specificity of dIVCmin in predicting PIH were 0.69 and 0.66 respectively, and the AUSROC was 0.72. In subgroup analysis, the AUSROC of IVCCI in predicting PIH in etomidate subgroup and non-immediate measurement before induction subgroup was 0.92 and 0.71 respectively. The AUSROC of IVCCI was all between 0.8 and 0.9 in propofol group, fentanyl group, sufentanil group, ARB/ACEI group, unlimited surgical types group, and combined with vascular diseases group and other subgroups. Conclusions:IVCCI measured by ultrasound can moderately predict PIH, and dIVCmax and dIVCmin have low accuracy in predicting PIH. Immediate measurement before induction and use of etomidate can improve the predictive accuracy of IVCCI. The predictive accuracy of IVCCI is not affected by the type of opioid drugs, type of surgery, use of ARB/ACEI antihypertensive drugs or vascular diseases.

Objective To evaluate the role of P2Y₁₂ receptor in microglia in central post-stroke pain (CPSP) in mice and its mechanism. Methods Thirty-two specific pathogen-free(SPF)-grade male C57BL/6J mice were selected, aged 7 to 8 weeks, weighing 25 to 30 g, were divided into four groups using a random number table method: C group (sham operation group, n=8), CPSP group (n=8), CPSP-M group (CPSP plus P2Y₁₂ receptor inhibitor MRS2395, n=8) and C-M group (sham operation plus P2Y₁₂ receptor inhibitor MRS2395, n=8). CPSP model was induced by injecting 10 nL type Ⅳ collagenase(0.001 U/nL) into the right ventral posterior medial nucleus andventral posterior lateral nucleus. MRS2395(1.5 mg/kg) was injected intraperitoneally at 30 min before model preparation in CPSP-M group and C-M group and then injected once a day for 5 consecutive days, mice in C group and CPSP group were given saline at the same volume. Before the modeling (T₀) and 3, 7 and 14 days (T₁, T₂, T₃) after the establishment of the model, the thermal withdrawal latency (TWL), cold withdrawal latency (CWL) and paw withdrawal frequency (PWF) were measured. The mice were then sacrificed and the brain tissues were obtained for observing the location of P2Y₁₂receptor by double immunofluorescence staining and the pathological changes by HE staining, and for determination of the expression levels of P2Y₁₂ receptor, toll-like receptor 4 (TLR4), phospho-nuclear factor-κB p65 (p-NF-κB p65) and NF-κB p65 by western blot. Results P2Y₁₂ receptor was co-localized only with microglia, but not with neurons or astrocytes in brain tissue of CPSP group. Compared with C group, the TWL and CWL were significantly reduced and the PWF was significantly increased at T₁ to T₃, cerebral injury was aggravated significantly and the expressions of P2Y₁₂ receptor, TLR4 and p-NF-κB p65 in brain tissue were up-regulated in CPSP group and CPSP-M group (P < 0.05). There was no statistically significant difference between C group and C-M group in the above indicators (P>0.05). Compared with CPSP group, the TWL and CWL were significantly prolonged and the PWF was significantly reduced at T₁ to T₃, cerebral injury was relieved significantly and the expressions of P2Y₁₂ receptor, TLR4 and p-NF-κB p65 in brain tissue were down-regulated in CPSP group and CPSP-M group (P < 0.05). Conclusion P2Y₁₂ receptors in microglia may be involved in the development of CPSP by activating TLR4/NF-κB signaling pathway in mice.

Objective:To observe the effect of ventilator-induced lung injury (VILI) on blood-brain barrier permeability in rats.Methods:Forty-eight healthy clean male Sprague-Dawley (SD) rats were randomly divided into sham operation (Sham) group, low tidal volume (LVT) mechanical ventilation group (LVT group), normal tidal volume (NVT) mechanical ventilation group (NVT group) and high tidal volume (HVT) mechanical ventilation group (HVT group) with 12 rats in each group. After anesthesia, rats in the Sham group were intubated and kept spontaneous breathing. The rats in different tidal volume (VT) groups were mechanically ventilated by endotracheal intubation with VT of 6 mL/kg (LVT group), 10 mL/kg (NVT group), and 20 mL/kg (HVT group), respectively. The inspiration-expiration ratio of the three groups was 1∶1, the ventilation frequency was 40 times/min, and the ventilation time was 3 hours. At the end of the experiment, the bronchoalveolar lavage fluid (BALF) of rats was collected, and the levels of pro-inflammatory factors [tumor necrosis factor-α (TNF-α), interleukins (IL-1β and IL-6)] in BALF were detected by enzyme-linked immunosorbent assay (ELISA). The lung tissues of rats were collected, and the lung wet/dry weight (W/D) ratio was calculated. The pathological changes of lung tissues were observed under light microscopy after hematoxylin-eosin (HE) staining, and lung injury scores were performed. The brain tissue of rats was taken to measure the brain water content, and the Evans blue (EB) content of brain tissue was measured to reflect the permeability of the blood-brain barrier. The tight junction proteins in the brain tissues were detected by Western blotting.Results:After 3 hours of mechanical ventilation, with the increase of VT, the degree of lung injury in VILI rats gradually increased. When VT reached 20 mL/kg, lung tissue structure was significantly injured, alveolar wall edema, alveolar congestion, lung interstitial thickening, a large number of inflammatory cells infiltrated, and the lung injury score, lung W/D ratio, and the levels of TNF-α, IL-1β and IL-6 in BALF were significantly higher than those in the Sham group [lung injury score: 10.6±1.1 vs. 1.4±1.0, lung W/D ratio: 6.6±0.8 vs. 3.7±0.6, TNF-α(ng/L): 832.9±97.9 vs. 103.8±23.3, IL-1β (ng/L): 68.9±14.1 vs. 15.7±2.6, IL-6 (ng/L): 70.8±16.4 vs. 20.3±5.4, all P < 0.05]. Lung injury in rats was accompanied by aggravating brain injury. When VT reached 20 mL/kg, brain water content and EB content in brain tissue were significantly higher than those in the Sham group [brain water content: (85.4±3.6)% vs. (68.7±2.7)%, EB content in brain tissue (μg/g): 887±78 vs. 97±14, both P < 0.05], and the protein expressions of claudin-5, occluding and zonula occluden-1 (ZO-1) in the brain tissue were significantly lower than those in the Sham group [claudin-5 protein (claudin-5/β-actin): 0.67±0.12 vs. 1.45±0.19, occludin protein (occludin/β-actin): 0.48±0.11 vs. 0.99±0.21, ZO-1 protein (ZO-1/β-actin): 0.13±0.03 vs. 0.63±0.12, all P < 0.05]. Conclusion:VILI can induce brain edema and increase blood-brain barrier permeability in rats, which may be related to the down-regulation of tight junction protein expression in the brain tissue.

Objective:To evaluate the effect of open-lung strategy (OLS) on postoperative delirium (POD) in elderly patients undergoing laparoscopic surgery.Methods:Seventy-four elderly patients of both sexes, aged 65-80 yr, with body mass index of 18.5-30.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing elective laparoscopic radical rectal cancer or radical prostate cancer surgery under general anesthesia, were divided into 2 groups ( n=37 each) by the random number table method: OLS group and non-OLS (NOLS) group. Patients in OLS group received small tidal volume ventilation, recruitment maneuvers, and individualized positive end-expiratory pressure. Fixed positive end-expiratory pressure 5 cmH 2O was given in NOLS group. Cerebral regional oxygen saturation (rSO 2), pH value, PaO 2, PaCO 2 and PaO 2/FiO 2 were recorded before induction of anesthesia (T 0, baseline value), at 10 min after tracheal intubation (T 1), at 1 and 2 h after pneumoperitoneum (T 2, 3) and at 10 min after extubation (T 4). The levels of serum interleukin-6 (IL-6), IL-10 and calcium-binding protein (S100β) were measured by enzyme-linked immunosorbent assay before surgery, at the end of surgery, and at 1 day after surgery. The development of POD was assessed using the delirium assessment scale at 1-3 days after surgery. Results:Compared with NOLS group, the pH value was significantly decreased at T 3, PaCO 2 was increased, PaO 2, PaO 2/FiO 2 and rSO 2 were increased at T 2-4, serum IL-6 and S100β concentrations were decreased after surgery and at 1 day after surgery, the serum IL-10 concentration was increased, and the incidence of POD was decreased in OLS group ( P<0.05). Conclusions:OLS can increase rSO 2, reduce the systemic inflammatory response, and decrease the risk of POD in elderly patients undergoing laparoscopic surgery.