Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

AIM: To explore the clinical therapeutic effect of teprotumumab combined with glucocorticoid pulse therapy for thyroid-associated ophthalmopathy(TAO), and its impacts on thyroid function, levels of inflammatory factors, and adverse reactions in patients. METHODS: Active TAO patients admitted to the Ophthalmology Department were enrolled and randomly divide into the steroid group and the combined group. Then the steroid group was treated with glucocorticoid pulse therapy, while the combined group was combined with intravenous infusion of teprotumumab on the basis of the steroid group. The clinical therapeutic effect, the CAS, OSDI, M-C-TAO-QOL scores, ocular sign indicators(fissure width, proptosis), levels of inflammatory factors(TNF-α, CRP, IL-17), thyroid function(TSH, FT3, FT4)before and after treatment, and occurrence of adverse reactions were compared between two groups.RESULTS:Totally 96 TAO patients(192 eyes)were included, with 48 cases(96 eyes)in each group. In the combined group, there were 17 males and 31 females, with an average age of 51.85±3.53 y; in the steroid group, there were 14 males and 34 females, with an average age of 51.26±3.84 y. The total effective rate of the combined group(94%)was higher than that of the steroid group(79%)(P<0.05). After treatment, the CAS score, OSDI score, fissure width, proptosis, levels of TNF-α, CRP, and IL-17 in the combined group were all lower than those in the steroid group, and the M-C-TAO-QOL score was higher than that in the steroid group(P<0.05). However, there was no difference in thyroid function indicators and adverse reactions between two groups after treatment(P>0.05). CONCLUSION: The combination of teprotumumab and glucocorticoid pulse therapy for TAO has a prominent therapeutic effect. Meantime, it can more effectively control ocular inflammation, improve ocular signs and quality of life of patients, and has no obvious adverse effect on thyroid function, with controllable safety.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

Objective:To explore the efficacy and safety of instantly generated inhaled nitric oxide (iNO) for treating neonatal pulmonary hypertension (PH) complicated with severe hypoxic respiratory failure.Methods:This single-center, single-arm, prospective study included 32 neonates with PH complicated with hypoxic respiratory failure who were hospitalized in the neonatal intensive care unit (NICU) of Beijing Children′s Hospital Affiliated to Capital Medical University from March 2023 to March 2025 and received immediate iNO generation therapy. The demographic data, maternal pregnancy, mechanical ventilation parameters, arterial blood gas indexes, other hospitalization data and safety indexes of iNO treatment were collected. The time point for starting iNO treatment was set as 0 h, and the observation time points were 1, 6, 12, 24, 48 h after treatment and when iNO treatment was stopped. The positive reaction of iNO treatment was defined as the decrease of oxygenation index (OI)>10% or the increase of arterial partial pressure of oxygen (PaO 2)>10% after treatment. The OI, mechanical ventilation parameters, arterial blood gas index changes and treatment positive reaction ratio were analyzed to evaluate the effectiveness of iNO treatment, and the nitrogen dioxide concentration, methemoglobin (MetHb) concentration and other indicators were analyzed to evaluate the safety of iNO treatment. Paired t test or Wilcoxon signed rank sum test was used to compare the observation indexes at different treatment times. Friedman test was used to compare the concentration of nitrogen dioxide and MetHb at multiple treatment times. Receiver operating characteristic (ROC) curve was used to analyze the best cut-off value of OI related indexes to distinguish the treatment outcome of iNO. Results:Among 32 neonates, 18 (56%) were males and 14 (44%) were females, the gestational age was 38 (35, 39) weeks, the birth weight was 3.1 (2.3, 3.4) kg, and the age of enrollment was 3 (2, 8) days. The OI and the mean airway pressure at 48 h after treatment were both lower than those at 0 h ((10.4±2.0 vs. 22.6±2.5, 13.0 (12.0, 14.0) vs. 14.0 (13.0, 16.0) cmH 2O, 1 cmH 2O=0.098 kPa, both P<0.05). The fraction of inspired oxygen at 24 and 48 h after treatment were both lower than those at 0 h (both P<0.05). The PaO 2 at 6, 12, 24 and 48 h after treatment were all higher than those at 0 h (all P<0.05). The proportion of positive reactions to iNO treatment was 20 neonates (63%), 22 neonates (69%), 23 neonates (72%), 23 neonates (72%) and 26 neonates (8%) at 1, 6, 12, 24, 48 h after treatment, respectively. No occurrence of methemoglobinemia, excessive nitrogen dioxide concentration, or device related adverse events were observed. Out of 32 neonates, a total of 24 neonates (75%) were cured or improved and discharged according to medical advice, while 8 neonates (25%) died in the hospital. The best cut-off value of OI at 0 h and the decline range of OI at 12 h to distinguish the outcome of hospitalization were 24.8 and 22.2%, respectively. Conclusion:It was effective and safe to use instantly generated iNO to treat neonatal PH with severe hypoxic respiratory failure.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

Objective:The clinical symptoms of children with global developmental delay (GDD) were analyzed to provide the scientific basis for the intervention of children with GDD.Methods:The results of the neuro-psychobehavioral scale were collected from 32 511 children with GDD from June 2020 to November 2023. Inclusion criteria: Children diagnosed with GDD according to the Diagnostic and Statistical Manual of Mental Disorders-V, ages 0.0 to 4.9 years. Exclusion criteria: children with common hearing impairment and visual impairment. The Chi-square tests were used for statistical analysis.Results:There were more boys than girls with GDD in outpatient clinics (68.2% vs. 31.8%). Among the children, the proportion of developmental delay in 5, 4, 3, and 2 domains was 31.1%, 23.4%, 22.9% and 22.6% respectively. The rate of delay in 2-3 domains was lower in boys (41.9%) than in girls (53.1%). The rate of delay in 4-5 domains was higher in boys (58.1%) than in girls (46.9%) ( χ2=352.11, P<0.001). Overall, outpatient GDD decreased with age. From 1.0-1.9 to 4.0-4.9 years of age, the proportion of children with developmental delay in 5 domains increased with age (18.2%, 36.4%, 43.9%, 52.4%). Among children aged 0.0-0.9 years, the proportion of 2 domains of developmental delay was higher (33.4%).Among children aged 1.0-1.9 years, the proportion of 2-3 domains of developmental delay was higher (30.7%). Among children aged 2.0-, 3.0-, 4.0-4.9 years, the proportion of developmental delay in 5 domains was higher (36.4%, 43.9%, 52.4%). In children with GDD, the fine motor delay occurred most frequently (85.1%), followed by social self-care (83.9%), language (79.0%), adaptation (62.3%), and gross motor (52.8%). The frequency of developmental delays in fine motor, adaptability, language, and social self-care in boys was higher than that in girls ( χ2=161.37, χ2=41.10, χ2=320.90, χ2=238.54, all P<0.001). The age groups with the highest delay incidence of gross motor, fine motor, adaptability, language, and social self-care were: 4.0-4.9 years (70.6%), 3.0-3.9 years (97.4%), 4.0-4.9 years (81.2%), 2.0-2.9 years (90.9%),2.0-2.9 years (95.4%). The proportions of fine motor delay in GDD children aged 0.0-0.9, 3.0-3.9 and 4.0-4.9 years were (74.5%, 97.4%, 96.8%) and the proportions of social self-care delay in GDD children aged 1.0- and 2.0-2.9 years were (92.1%, 95.4%). Peripheral and mild developmental delays were predominant in children with GDD. The proportion of severe language delay (6.4%) was higher than that in other fields. Conclusions:The proportion of GDD children with developmental delay in 4-5 domains was 54.5%. The most frequent domain of delay was fine motor. The frequencies of developmental delays in fine motor skills, adaptability, language, and social self-care in boys were higher than in girls. Most of the developmental delays in GDD children were marginal and mild. The rate of severe developmental delay in language was higher than in other domains.

The patient is a 63-year-old man with a history of chronic illness, presenting with intermittent low-grade fever, recurrent dry cough, and shortness of breath upon exertion. Lung CT showed a nodule in the left lung and a large mass in the right lung with liquefactive necrosis and an air-fluid level accompanied by pleural effusion. Laboratory findings showed significantly increasedf immunoglobulin G (IgG), IgG4, and total immunoglobulin E, along with a mild increase in eosinophils, and moderate elevations in erythrocyte sedimentation rate and high-sensitivity C-reactive protein. Malignant tumors, immunological, and hematological diseases were ruled out. Various antibiotic treatments were ineffective and the condition was recurrent. Conventional methods failed to identify the pathogen. Metagenomic next-generation sequencing (mNGS) technology was used to detect Mycobacterium monacense from lung tissue. Targeted antibiotic treatment was effective with no further episodes of low-grade fever and alleviation of dry cough symptoms. This case underscores the clinical significance of mNGS technology for the diagnosis and treatment of unexplained pulmonary infections, providing a useful reference for clinical diagnostic and treatment.

Objective:To analyze the changes of DNA methylation in peripheral blood mononuclear cells (PBMC) of patients with hepatocellular carcinoma (HCC) and to evaluate the clinical value of a combined model based on FSIP1 gene methylation on the early diagnosis of HCC.Methods:This is a case-control study. From May 2023 to September 2024, 183 HCC patients and 155 healthy controls were collected in Qilu Hospital of Shandong University. The selected study subjects were divided into three cohorts: 14 HCC patients and 39 healthy controls formed the discovery cohort, a screening cohort consisted of 36 HCC patients and 39 healthy controls, 133 HCC patients and 77 healthy controls were included in the model construction cohort. 935k methylation chip analysis was used to identify specific differentially methylated sites in peripheral blood PBMC of the discovery cohort. The absolute value of the average methylation level difference between HCC group and healthy control group (|Δβ|) and P value were calculated. Then targeted bisulfite sequencing was used to verify the differentially methylated sites in the screening cohort. Finally, based on MethylTarget methylation sequencing technology, differential methylation sites were further verified in model construction cohort (divided into training set and validation set, training set consisted of 99 HCC patients and 57 healthy controls; validation set consisted of 34 HCC patients and 20 healthy controls). HCC early diagnosis model was constructed by random forest algorithm combined with clinical parameters and the diagnostic performance of the model was evaluated by receiver operating characteristic (ROC) curve in the validation set. Results:The total of 7 249 differentially methylated sites between HCC patients and healthy controls in discovery cohort were selected under the rule of |Δβ|≥0.06 and P<0.01. Among them, the cg02155073 site located on FSIP1 was hypermethylated in PBMC of HCC patients in the screening cohort and model cohort ( P<0.001). The AUC of HCC early diagnosis model (FmAP) based on FSIPI in the validation set was 0.967 (95% CI 0.924-1.000); sensitivity was 88%, specificity was 95%. The model had good diagnostic efficacy for patients with early HCC, stage Ⅰ-Ⅱ HCC AUC was 0.958 (95% CI 0.898-1.000). The FmAP model also had diagnostic value for tumor size <2 cm HCC and AFP negative HCC, with AUC of 0.955 (95% CI 0.898-1.000) and 0.964 (95% CI 0.934-0.994).The sensitivity were 92% and 93% and specificity both were 84%. Conclusion:The FmAP model based on FSIP1 gene methylation has good clinical value for the early diagnosis of hepatocellular carcinoma.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets