OBJECTIVE: To explore the effects of different endotracheal tube cuff pressure management modes on cuff sealing and the pressure exerted on the tracheal wall. METHODS: A prospective self-controlled study was conducted. Eleven patients undergoing endotracheal intubation and mechanical ventilation with an automatic airway management system (AGs) admitted to the Second Medical Centre of the Chinese People's Liberation Army General Hospital from October 1, 2020, to April 1, 2022, were enrolled as the study subjects. Within 24 hours after the establishment of artificial airway and mechanical ventilation, four cuff pressure management modes were randomly applied to each patient for 24 hours in sequence: automatic cuff pressure management mode [modeI: the safe range of cuff pressure was set at 20-35 cmH₂O (1 cmH₂O≈0.098 kPa), and the CO₂ pressure above the endotracheal tube cuff was automatically detected by AGs every 5 minutes to determine the cuff sealing status, and the cuff pressure was automatically adjusted], constant cuff pressure (25 cmH₂O) management mode (mode II: the cuff pressure was monitored by AGs through a pressure sensor, and the cuff pressure was maintained at 25 cmH₂O via a pressure pump), constant cuff pressure (30 cmH₂O) management mode (mode III: the cuff pressure was monitored by AGs through a pressure sensor, and the cuff pressure was maintained at 30 cmH₂O via a pressure pump), and manual cuff pressure management mode (mode IV: the cuff pressure was manually measured by nurses every 6-8 hours using a cuff pressure gauge to keep the cuff pressure at 25-30 cmH₂O after inflation). The CO₂ pressure above the endotracheal tube cuff (at 60-minute intervals) and the cuff pressure changes (at 50-ms intervals) were recorded to compare the differences in number of cuff leaks [no leak was defined as CO₂ pressure = 0, small leak as 0 < CO₂ pressure < 2 mmHg (1 mmHg≈0.133 kPa), and large leak as CO₂ pressure ≥ 2 mmHg] and cuff pressure among modesI-IV. RESULTS: A total of 24 CO₂ pressure measurements were taken per patient across the four modes, resulting in a total of 264 detections for each mode. Regarding the cuff leak, the total number of leak and large leak in modeIwas significantly lower than that in modes II-IV [total leak: 30 cases (11.36%) vs. 81 cases (30.68%), 70 cases (26.52%), 103 cases (39.02%); large leak: 15 cases (5.68%) vs. 50 cases (18.94%), 48 cases (18.18%), 66 cases (25.00%), all P < 0.05]. There was no significant difference in the number of cuff leak between modes II and III, and mode IV had the most severe cuff leak. In terms of cuff pressure, since mode IV required blocking the cuff tube from the AGs tube and the AGs cuff pressure management module did not actually work, real-time monitoring of cuff pressure was not possible. Therefore, cuff pressure changes were only analyzed in modes I-III. Each of the 11 patients underwent 24-hour cuff pressure monitoring under modes I-III, with 19 008 000 monitoring times for each mode. The cuff pressure in mode I was between that in modes II and III [cmH₂O: 27.09 (26.10, 28.14) vs. 26.60 (25.92, 27.47), 31.01 (30.33, 31.88), both P < 0.01]. Moreover, the number of extreme values of cuff pressure > 50 cmH₂O in mode I was significantly lower than that in modes II and III [19 900 cases (0.105%) vs. 22 297 cases (0.117%), 27 618 cases (0.145%), both P < 0.05]. CONCLUSION Dynamically monitoring the CO₂ pressure above the cuff to guide the adjustment of endotracheal tube cuff pressure can achieve better cuff sealing with a relatively lower cuff pressure load.
Humans ; Intubation, Intratracheal/instrumentation* ; Pressure ; Prospective Studies ; Respiration, Artificial ; Male ; Airway Management/methods* ; Female ; Middle Aged

Objective To analyze the incidence,colonization pathways,and predictive factors of bacterial colonization of epidural analgesia catheters in patients with chronic pain.Methods A total of 150 patients with chronic pain who underwent continuous epidural catheterization(catheter in-dwelling time of 7 to 10 days)were selected as study subjects.Samples from three sites were collect-ed for bacterial culture.Clinical data of the patients were collected,and the positive rate of bacterial culture,characteristics of bacterial species distribution,and bacterial colonization pathways were ana-lyzed.The efficacy of predictive factors was assessed using the receiver operating characteristic(ROC)curve.Results The positive rates of bacterial culture in samples from the skin swabbing fluid around the puncture site,the subcutaneous segment of the catheter,and the catheter tip were 22.0％,7.3％,and 8.7％,respectively.Staphylococcus epidermidis was the predominant colonizing bacterial species.Spearman correlation coefficient analysis showed a significant correlation between the results of bacterial culture from the skin around the puncture site and catheter tip colonization(r=0.47,P＜0.01).ROC curve analysis revealed that the area under the curve of bacterial culture results from the skin around the puncture site in predicting catheter tip bacterial colonization was 0.843,with a sensitivity of 84.9％and a specificity of 84.6％.Conclusion Bacterial migra-tion along the catheter is the main pathway for catheter tip bacterial colonization,and the results of bacterial culture from the skin around the puncture site are an effective predictive factor for the risk of bacterial colonization.

Objective : To analyze the differential expression profile of miRNAs in amniotic fluid exosomes of fetu- ses with Down syndrome (DS) and provide insights for identifying novel biomarkers for the prenatal diagnosis of DS . Methods : Amniotic fluid samples were collected from fetuses with DS and chromosomally normal fetuses . Exo- somes were isolated from the amniotic fluid and subjected to high-throughput sequencing. Differentially expressed miRNAs were identified , and target genes were predicted using TargetScan and miRanda. Target genes located on chromosome 21 were selected , and their biological functions and associated diseases were analyzed using Gene- Cards , HGNC , NCBI Gene , UniProtKB/Swiss-Prot , Ensembl , and OMIM databases . GO and KEGG enrichment analyses were performed to investigate the biological functions of the enriched genes . Results : A total of 59 differ- entially expressed miRNAs were identified , including 31 upregulated and 28 downregulated miRNAs . Based on a fold change > 2 and P < 0. 05 , 10 upregulated and 9 downregulated miRNAs with the highest expression levels were selected . Key miRNAs included hsa-let-7b-5p , hsa-let-7c-5p , hsa-let-7b-3p _ 1ss22CT , and hsa-miR-199b-5p , with BACH1 and IFNAR1 identified as their shared target genes . GO analysis revealed that the enriched target genes were primarily involved in protein binding , metal ion binding , transferase activity , DNA binding , transcriptional regulation by RNA polymerase Ⅱ , and nucleotide binding. KEGG pathway analysis indicated that the target genes were mainly associated with metabolic pathways , cancer-related pathways , the PI3K-Akt signaling pathway , and the Rap1 signaling pathway . Conclusion Differential expression of miRNAs in amniotic fluid exosomes was ob- served between DS fetuses and those with normal karyotypes . Combined analysis with placental miRNAs revealed hsa-miR-199b-5p as a common differentially expressed miRNA in both DS amniotic fluid and placenta. It is hypoth- esized that BACH1 and IFNAR1 , shared target genes of hsa-miR-199b-5p , hsa-let-7b-5p , hsa-let-7c-5p , and hsa- let-7b-3p_1ss22CT , may play a role in the pathogenesis of DS .

OBJECTIVE To observe the short-term efficacy and safety of venetoclax combined with homoharringtonine and cytarabine in the treatment of acute myeloid leukemia （AML）. METHODS The data of 40 newly diagnosed AML patients admitted to our hospital from October 2022 to November 2023 were retrospectively collected and divided into observation group and control group according to treatment plan， with 20 cases in each group. The patients in the control group were given Daunorubicin hydrochloride for injection+Cytarabine for injection， and the patients in the observation group were given Venetoclax tablets+ Homoharringtonine injection+Cytarabine for injection. The patients in both groups were given relevant medicine， with 28 days as one cycle. The short-term efficacy， negative rate of minimal residual disease （MRD）， duration of granulocyte deficiency， duration of platelet （PLT） ＜20×109 L－1， transfusion volume of suspended red blood cells and platelet， and the occurrence of adverse drug reactions were evaluated in both groups after 1 cycle of induction chemotherapy. RESULTS The complete remission or complete remission with incomplete hematologic recovery （CR/CRi） rate in the observation group was significantly higher than control group （P＜0.05）， and the negative rate of MRD in the observation group was also significantly higher than control group （P＜0.05）. However， in low-， medium- and high-risk patients， there was no statistical significance in CR/CRi rates between the two groups （P＞0.05）. There were no significant differences in the duration of agranulocytosis， the duration of PLT ＜20×109 L－1， the amount of suspended red blood cell transfusion， the amount of platelet transfusion， the incidence of hematologic toxicity and the incidence of non-hematologic toxicity between 2 groups （P＞0.05）. CONCLUSIONS Venetoclax combined with homoharringtonine and cytarabine show good short-term efficacy and safety in the treatment of AML.

Lipophosphatidic acid(LTA)was used to stimulate Mac-T cells,and the expression lev-els and phosphorylation levels of key proteins of nuclear factor-κB(NF-κB)and mitogen-activated protein kinase(MAPK)signaling pathway and the expression levels of upstream key action factors TLR4 and MyD88 proteins were detected by Western blot,and EDU assay was used to detect cell proliferation levels and flow cytometry was used to detect apoptosis.The results showed that acti-vation of GPR120 significantly decreased the phosphorylation levels of LTA-induced NF-κB(P65 and IκBα)(P＜0.01)and MAPK(JNK,ERK,p38)(P＜0.01)in Mac-T cells;inhibition of GPR120 was able to upregulate LTA-induced NF-κB(p65 and IκBα)in Mac-T cells(P＜0.01)and MAPK(JNK,ERK,p38)phosphorylation levels(P＜0.01);and activation of GPR120 significantly allevia-ted LTA-induced upregulation of TLR4 and MyD88(P＜0.01);inhibition of GPR120 significantly exacerbated LTA-induced upregulation of TLR4 and MyD88(P＜0.05);LTA stimulation led to a trend of diminished Mac-T cell proliferation and significantly increased apoptosis,whereas activa-tion of the GPR120 gene significantly increased cell activity(P＜0.01),promoted cell proliferation and significantly reduced apoptosis(P＜0.05)thereby alleviating the damage to Mac-T cells by LTA;LTA stimulation led to a highly significant increase in apoptosis(P＜0.01).In contrast,acti-vation of the GPR120 gene significantly reversed the increase in the apoptosis rate of Mac-T cells induced by LTA(P＜0.01),while inhibition of the GPR120 gene enhanced the apoptosis-promo-ting effect of LTA(P＜0.05),indicating that activation of the GPR120 gene attenuated the in-crease of apoptosis rate caused by LTA-induced inflammatory Mac-T cells.The results suggest that GPR120 can regulate inflammation by mediating TLR4 and MyD88 expression to inhibit NF-κB/MAPK inflammatory pathway activation and can promote cell proliferation.

Objective:To analyze clinical, immunopathological, therapeutic, and prognostic features of epidermolysis bullosa acquisita (EBA) .Methods:A retrospective study was conducted on patients with confirmed EBA at the Department of Dermatology, West China Hospital, Sichuan University from January 1, 2015 to July 30, 2022. Their clinical, immunopathological, therapeutic and prognostic features were analyzed. The autoimmune bullous skin disorder intensity score (ABSIS) was used to assess the severity of lesions in patients with EBA, and the visual analogue scale (VAS) to assess itch intensity. Descriptive statistical analysis was primarily carried out, and the correlation between disease severity scores and itch scores was analyzed using Pearson correlation analysis.Results:A total of 13 patients with EBA were included, including 9 males and 4 females, with the age at the clinic visit being 49.0 ± 20.6 years and ABSIS scores being 24.2 ± 10.7 points. One patient was diagnosed with classical EBA, while the remaining 12 patients with inflammatory EBA. Mucosal involvement was observed in 6 cases, whose oral mucosae were all affected. All patients had itching to varying degrees, with VAS scores of 5.6 ± 2.2 points; 9 of the 12 inflammatory EBA patients had VAS scores of ≥ 5 points, whereas 1 classical EBA patient had a VAS score of 2 points; there was no significant correlation between the ABSIS scores and VAS scores ( r = -0.02, P > 0.05). Histopathological examination showed subepidermal cleavages or blister formation and varying degrees of perivascular inflammatory cell infiltration in the superficial dermis of patients with inflammatory EBA. Direct immunofluorescence assay demonstrated linear IgG deposits along the basement membrane zone in all 13 patients, including 12 with concomitant linear C3 deposits in the basement membrane zone, 5 with linear IgA deposits, and 2 with IgM deposits. Indirect immunofluorescence on salt-split skin showed IgG deposition on the dermal side of the salt-split skin in the 13 patients. An elevated eosinophil count in the peripheral blood was observed in 1 out of 11 patients, while increased total IgE levels were noted in 3 out of 9 patients. Among the 13 EBA patients, 11 were treated with systemic glucocorticoids (equivalent to 10 - 100 mg/d of prednisone), and the other 2 were treated with compound glycyrrhizin tablets, sulfasalazine, hydroxychloroquine sulfate, and minocycline hydrochloride alone or in combination. During the follow-up period of 34.0 (27.5, 66.0) months in the 13 patients, 8 achieved complete remission after drug withdrawal, 2 achieved complete remission on therapy, 1 achieved partial remission on minimal therapy, and 2 presented with uncontrolled condition. The time to complete remission off/on therapy was 6.0 (3.8, 17.5) months. Conclusions:The inflammatory phenotype seems to be relatively common in EBA patients, with itching to varying degrees, and oral mucosa was the most commonly involved mucosa in those with mucosal damage. After treatment with systemic glucocorticoids alone or in combination with immunomodulators, most patients could achieve complete remission.

OBJECTIVES: The prevalence of human immunodeficiency virus (HIV) associated neurocognitive disorders (HAND) in people living with HIV/acquired immunodeficiency syndrome (PLWHA) worldwide is as high as 42.6%. This study aims to investigate the neurocognitive function status and its influencing factors in PLWHA, providing evidence for early identification and intervention of neurocognitive impairment in this population. METHODS: PLWHA aged 18 and above who received outpatient or inpatient care at the First Hospital of Changsha between June and August 2019 were included. Sociodemographic and HIV-related information were collected. Neurocognitive function was assessed using the Brief Neurocognitive Screen (BNCS), which includes the Digit Symbol Test (DST) and Trail Making Test A and B (TMT-A and TMT-B). Impaired neurocognitive function was defined as abnormal scores in at least one dimension (DST score <30, TMT-A time >60 seconds, TMT-B time >90 seconds). RESULTS: A total of 375 PLWHA were included, of whom 212 (56.5%) exhibited neurocognitive impairment. Higher impairment rates were observed among females, individuals aged ≥50 years, those with primary education or below, and those who were married/cohabiting (all P<0.05). Heterosexual transmission accounted for the majority of infections (233 cases, 62.1%), with a significantly higher rate of neurocognitive impairment (69.1%) compared to homosexual transmission and unknown routes (P<0.001). Higher WHO clinical stages were associated with increased impairment rates (P<0.001). PLWHA with a nadir CD4⁺ T cell count <200 cells/mm³ or an infection duration ≥5 years had significantly higher impairment rates than those with higher CD4⁺ T cell count or shorter infection durations (both P<0.05). Logistic regression analysis showed that patients with a nadir CD4⁺ T cell count <200 cells/mm³ had a significantly higher risk of neurocognitive impairment (OR=2.461, 95% CI 1.116 to 5.427). Compared to WHO stage I, the risk increased progressively in stage II (OR=6.005, 95% CI 2.906 to 12.407), stage III (OR=6.989, 95% CI 2.502 to 19.523), and stage IV (OR=22.059, 95% CI 7.289 to 66.760; all P<0.05). CONCLUSIONS Potential risk factors for neurocognitive impairment in PLWHA include low nadir CD4⁺ T cell counts and advanced WHO clinical stages. The lower the CD4⁺ T cell count and the higher the clinical stage, the greater the risk of neurocognitive dysfunction.
Humans ; Female ; Male ; Middle Aged ; HIV Infections/psychology* ; Adult ; Acquired Immunodeficiency Syndrome/psychology* ; Neuropsychological Tests ; Cognitive Dysfunction/epidemiology* ; Neurocognitive Disorders/epidemiology* ; CD4 Lymphocyte Count ; Risk Factors ; Aged

Objective Some colorectal cancer patients still face high recurrence rates and poor prognoses even after they have undergone the surgical treatment of radical resection.Identifying potential biochemical markers and therapeutic targets for the prognostic evaluation of patients undergoing radical resection of colorectal cancer is crucial for improving their clinical outcomes.Recently,it has been reported that the T cell immunoglobulin and mucin domain protein 3(Tim-3)and its ligand galactose lectin 9(galectin-9)play crucial roles in immune dysfunction caused by various tumors,such as colorectal cancer.However,their expressions,biological functions,and prognostic value in colorectal cancer are still unclear.This study aims to investigate the relationship between Tim-3 and galectin-9 expression levels and the clinicopathological characteristics and prognosis of patients undergoing radical resection of colorectal cancer.Methods A total of 171 patients who underwent radical resection of colorectal cancer at Chengdu Fifth People's Hospital between February 2018 and March 2019 were selected.Immunohistochemistry was performed to assess the expression levels of Tim-3 and galectin-9 in the cancer tissue samples and the paracancerous tissue samples of the patients.The relationship between Tim-3 and galectin-9 expression levels and the baseline clinical parameters of the patients was analyzed accordingly.Kaplan-Meier analysis was performed to assess the association between Tim-3 and galectin-9 expression levels and the relapse-free survival(RFS)and the overall survival(OS)of colorectal cancer patients.Cox regression analysis was conducted to identify factors associated with adverse prognosis in the patients.Results The immunohistochemical results showed that the high expression levels of Tim-3 and galectin-9 were observed in 70.18%(120/171)and 32.16%(55/171),respectively,of the colorectal cancer tissues,whereas the low expression levels were 29.82%(51/171)and 67.84%(116/171),respectively.Furthermore,the expression score of Tim-3 was significantly higher in colorectal cancer tissues than that in the paracancerous tissues,while the expression score of galectin-9 was lower than that in the paracancerous tissues(P＜0.05).Further analysis revealed that the expression of Tim-3 and galectin-9 was associated with the depth of tumor infiltration,vascular infiltration,and clinical staging(P＜0.05).During the follow-up period of 14-63 months,7 out of 171 patients were lost to follow-up.Among the remaining patients,49 and 112 cases presented abnormally low expression of Tim-3 and galectin-9,respectively,whereas 115 and 52 cases presented high expression of Tim-3 and galectin-9,respectively.Kaplan-Meier survival analysis demonstrated that patients with high Tim-3 expression in colorectal cancer tissues had significantly lower RFS and OS than those with low expression did(RFS:log-rank=22.66,P＜0.001;OS:log-rank=19.71,P＜0.001).Conversely,patients with low galectin-9 expression had significantly lower RFS and OS than those with high expression did(RFS:log-rank=19.45,P＜0.001;OS:log-rank=22.24,P＜0.001).Cox multivariate analysis indicated that TNM stage Ⅲ(HR=2.26,95%CI:1.20-5.68),high expression of Tim-3(HR=0.80,95%CI:0.33-0.91),and low expression of galectin-9(HR=1.80,95%CI:1.33-4.70)were independent risk factors affecting RFS and OS in patients(P＜0.05).Conclusion Aberrant expression of Tim-3 and galectin-9 is observed in colorectal cancer tissues.High expression of Tim-3 and low expression of galectin-9 are closely associated with adverse clinico-pathological characteristics and prognosis.They are identified as independent influencing factors that may trigger adverse prognostic events in patients.These findings suggest that Tim-3 and galectin-9 have potential as new therapeutic targets and clinical indicators.

Objective To evaluate the effect of preoperative pulmonary artery pressure on perioperative prognosis of the recipients with end-stage heart failure undergoing heart transplantation. Methods Clinical data of 105 recipients receiving heart transplantation were retrospectively analyzed. The mean pulmonary artery pressure (mPAP) was used as the diagnostic criterion. The optimal cut-off value of mPAP for predicting perioperative prognosis of heart transplant recipients was determined. According to the optimal cut-off value of mPAP, all recipients were divided into the low mPAP group (n=66) and high mPAP group (n=39). Intraoperative indexes (cardiopulmonary bypass time, aortic occlusion time, assisted circulation time and cold ischemia time of donor heart) and postoperative indexes [intra-aortic balloon pump (IABP) support rate, IABP support time, extracorporeal membrane oxygenation (ECMO) support rate, ECMO support time, mechanical ventilation time, length of ICU stay, incidence of moderate and severe tricuspid regurgitation and perioperative mortality rate] were compared between the low and high mPAP groups. The prognosis of the two groups was compared. Results The optimal cut-off value of mPAP in predicting clinical prognosis of heart transplant recipients was 30.5 mmHg. In the high mPAP group, the ECMO support rate and perioperative mortality rate were higher than those in the low mPAP group (both P < 0.05). No significant differences were observed in the cardiopulmonary bypass time, aortic occlusion time, assisted circulation time, cold ischemia time of donor heart, IABP support rate, IABP support time, ECMO support time, mechanical ventilation time, length of ICU stay and incidence of moderate and severe tricuspid regurgitation between two groups (all P > 0.05). No significant differences were noted in the 1-, 2-, 3- and 4- survival rates between two groups (all P > 0.05). Conclusions Preoperative mPAP in patients with end-stage heart failure is intimately correlated with perioperative prognosis of heart transplant recipients. The optimal cut-off value of mPAP in predicting perioperative prognosis of heart transplant recipients is 30.5 mmHg. In the high mPAP group, perioperative ECMO support rate and perioperative mortality rate are high, which do not affect the medium and long-term prognosis of the recipients undergoing heart transplantation.