Tumor cell-derived exosomes mediating hsa_circ_0001739/lncRNA AC159540.1 facilitate liver metastasis in colorectal cancer.

BACKGROUND: The current study probed into how tumor cell-derived exosomes (Exos) mediated hsa_circ_0001739/lncRNA AC159540.1 to manipulate microRNA (miR)-218-5p/FTO-N6-methyladenosine (m6A)/MYC signal axis in liver metastasis in colorectal cancer (CRC). METHODS: hsa_circ_0001739 and lncRNA AC159540.1 were identified as the upstream regulator of miR-218-5p using ENCORI and LncBase databases. Expression patterns of miR-218-5p, hsa_circ_0001739, lncRNA AC159540.1, FTO, and MYC were detected, accompanied by loss-and-gain-of function assays to examine their effects on CRC cell biological functions. SW480 cells-derived Exos were purified, followed by in vitro studies to uncover the effect of hsa_circ_0001739/lncRNA AC159540. RESULTS: miR-218-5p was downregulated while hsa_circ_0001739/lncRNA AC159540.1 was upregulated in CRC tissues and cells. Silencing of hsa_circ_0001739/lncRNA AC159540.1 restrained the malignant phenotypes of CRC cells. Exos-mediated hsa_circ_0001739/lncRNA AC159540.1 competitively inhibited miR-218-5p to elevate FTO and MYC. The inducing role of Exos-mediated hsa_circ_0001739/lncRNA AC159540.1 in CRC was also validated in vivo. CONCLUSION: Conclusively, Exos-mediated circ_0001739/lncRNA AC159540.1 regulatory network is critical for CRC, offering a theoretical basis for CRC treatment.

Hyper-expression and hypomethylation of TM4SF1 are associated with lymph node metastases in papillary thyroid carcinoma patients.

Lymph node metastases (LNM) are an indicator for recurrence in papillary thyroid carcinoma (PTC) patients. However, prophylactic neck dissection (ND) cannot improve survival or recurrence rate because of increased surgical complications and occult LNM. Biomarkers are needed for the prediction of high-risk of LNM to avoid unnecessary operation and reduce the missed malignant lymph nodules. GEO database was searched for the differentially expressed genes (DEGs) between PTC patients with LNM (N1) and those without LNM (N0), transcriptional and methylation data of DEGs in THCA were examined from databases. The expression and methylation of TM4SF1 in fresh and paraffin tissues of PTC patients were examined by qRT-PCR, IHC, and MSP. TM4SF1 was the only one significantly associated with LNM. UALCAN revealed that TM4SF1 was overexpressed and hypomethylated in LNM patients. MEXPRESS presented a negative correlation between gene expression and promoter methylation of TM4SF1. DEGs were enriched in multiple pathways and the Extracellular Matrix (ECM)-receptor interaction pathway showed the greatest correlation with LNM. IHC and qRT-PCR of tissues demonstrated that the expression of TM4SF1 in the N1 group was 4.5-fold higher than that in the N0 group (p<0.05). MSP exhibited that the positive rate of aberrant promoter methylation of TM4SF1 was 8.38% in N1 and 66.7% in N0 group (p<0.05). Hyper-expression and hypomethylation of TM4SF1 are associated with lymph node metastases in PTC patients.

Induction chemotherapy for the individualised treatment of hypopharyngeal carcinoma with cervical oesophageal invasion: a retrospective cohort study.

BACKGROUND: This study aimed to evaluate the potential of induction chemotherapy as an indicator of the management of advanced hypopharyngeal carcinoma with cervical oesophageal invasion. METHODS: Sixty-eight patients admitted to our hospital between February 2003 and November 2016 with stage IVB hypopharyngeal carcinoma with cervical oesophageal invasion were retrospectively analysed. Patients were divided into two groups according to the treatment they selected following an explanation of the different treatments available. Patients in group A received induction chemotherapy and had (1) complete/partial remission following chemotherapy and radiotherapy/concurrent chemoradiotherapy or (2) stable disease following chemotherapy and surgery. Patients in group B underwent surgery followed by adjuvant radiotherapy/concurrent chemoradiotherapy. Survival analyses were performed using the Kaplan-Meier method, and differences between the groups were evaluated using the log-rank test. Laryngeal and oesophageal retention rates were compared using the cross-tabulation test. RESULTS: The 3- and 5-year overall survival rates were 22.86% and 11.43% in group A and 24.25% and 6.06% in group B, respectively (all P > 0.05). The laryngeal and oesophageal retention rates were 40.0% and 74.3% in group A and 0.0% and 27.3% in group B, respectively (all P < 0.01). There was no statistically significant difference in the incidence of post-operative complications between the two groups (group A 8.6%, group B 12.1%; P > 0.05). CONCLUSIONS: Induction chemotherapy may be an appropriate first choice to ensure laryngeal and oesophageal preservation in the individualised treatment of advanced hypopharyngeal carcinoma with cervical oesophageal invasion.

Regulatory roles of Alu transcript on gene expression.

Alu element is the most successful transposon and it maintains a high level of content in primate genome. However, despite the fact that the expression level of independent Alu element is rather low under common condition, an increasing number of the observations for the Alu transcripts in cells and tissues have been reported recently. Alu transcripts play key roles in the network of gene expression regulation. The main functions of Alu transcript focus on gene regulation both at transcriptional and post-transcriptional levels. This review summarizes major functions of Alu transcripts on gene expression and highlights molecular mechanisms dependent on conserved sequence or secondary structure in order to unravel a relative ubiquitous way that Alu transcript uses to affect the whole genome.

Decreased expression of interleukin-36α correlates with poor prognosis in hepatocellular carcinoma.

Interleukin-36α (IL-36α) has been found to have a prominent role in the pathogenesis of inflammatory disorders; however, little is known about the role of IL-36α in cancer. In this study, we investigated the expression, prognostic value, and the underlying antitumor mechanism of IL-36α in hepatocellular carcinoma (HCC). From immunohistochemistry analysis, IL-36α expression was lower in poorly differentiated HCC cells. In clinicopathological analysis, low IL-36α expression significantly correlated with tumor size, histological differentiation, tumor stage, and vascular invasion, and low intratumoral IL-36α expression had significantly worse overall survival rates and shorter disease-free survival rates. Moreover, intratumoral IL-36α expression was an independent risk factor for overall survival. Consecutive sections were used to detect CD3+, CD8+, and CD4+ tumor-infiltrating lymphocytes (TILs), and we found that high-IL-36α-expressing tumor tissues exhibited a significantly higher proportion of intratumoral CD3+ and CD8+ TILs, but not CD4+ TILs. Our in vitro model confirmed that supernatant from IL-36α-overexpressing human HCC cells had an increased capacity to recruit CD3+ and CD8+ T cells. Consistently, mouse HCC cells engineered to overexpress IL-36α demonstrated markedly delayed growth in vivo, as well as higher levels of intratumoral CD3+ and CD8+ TILs, compared with control mice. In vitro chemotaxis analysis also showed that mouse HCC cells overexpressing IL-36α could recruit more number of CD3+ and CD8+ T cells. These results show that IL-36α expression may play a pivotal role in determining the prognosis of patients with HCC, which we attribute to the activation of adaptive T cell immunity, especially CD8+ T cell immune response.

Inhibitory Effects of 5-Aza-2'-Deoxycytidine and Trichostatin A in Combination with p53-Expressing Adenovirus on Human Laryngocarcinoma Cells.

OBJECTIVE: To investigate the effects of 5-Aza-2'-deoxycytidine (5-Aza-Cdr) and trichostatin A (TSA) combined with p53-expressing adenovirus (Ad-p53) on Hep-2 cell line in vivo and in vitro, in order to explore its possibility in biological treatment of laryngocarcinoma. METHODS: Effects of 5-Aza-Cdr and TSA in combination with Ad-p53 on Hep-2 cell line in vivo were determined by Cell Counting Kit-8 (CCK-8) assay. The effect of drug combination was calculated by Jin's formula. Effects on the cell line in vitro were investigated by establishing the nude mice model. RESULTS: 5-Aza-Cdr and TSA showed inhibitory effects on the proliferation of Hep-2 cells in dose- and time-dependent manner. Ad-p53 can inhibit the growth of Hep-2 cells in vivo and in vitro. However, the combination of epigenetic reagents (5-Aza-Cdr/TSA) and Ad-p53 was less effective than individual use of Ad-p53. 5-Aza-Cdr and Ad-p53 inhibited the growth of transplanted tumors and reduced the volume of tumors, and the tumor volume of Ad-p53 group was significantly smaller than that of the control group (P<0.05). CONCLUSION: Both epigenetic reagents (5-Aza-Cdr/TSA) and Ad-p53 can suppress cell proliferation on Hep-2 in vivo and in vitro and there may be some antagonistic mechanism between Ad-p53 and epigenetic reagents (5-Aza-Cdr/ TSA).

Prognostic and Predictive Value of a 15 Transcription Factors (TFs) Panel for Hepatocellular Carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most devastating diseases worldwide. Limited performance of clinicopathologic parameters as prognostic factors underscores more accurate and effective biomarkers for high-confidence prognosis that guide decision-making for optimal treatment of HCC. The aim of the present study was to establish a novel panel to improve prognosis prediction of HCC patients, with a particular interest in transcription factors (TFs). MATERIALS AND METHODS: A TF-related prognosis model of liver cancer with data from ICGC-LIRP-JI cohort successively were processed by univariate and multivariate Cox regression analysis. Then, for evaluating the prognostic prediction value of the model, receiver operating characteristic (ROC) curve and survival analysis were performed both with internal data from the International Cancer Genome Consortium (ICGC) and external data from The Cancer Genome Atlas (TCGA). Furthermore, we verified the expression of three genes in HCC cell lines by Western blot and qPCR and protein expression level by IHC in liver cancer patients' sample. Finally, we constructed a TF clinical characteristics nomogram to furtherly predict liver cancer patient survival probability with TCGA cohort. RESULTS: By Cox regression analysis, a panel of 15 TFs (ZNF331, MYCN, AHRR, LEF1, ZNF780A, POU1F1, DLX5, ZNF775, PLSCR1, FOXK1, TAL2, ZNF558, SOX9, TCFL5, GSC) was identified to present with powerful predictive performance for overall survival of HCC patients based on internal ICGC cohort and external TCGA cohort. A nomogram that integrates these factors was established, allowing efficient prediction of survival probabilities and displaying higher clinical utility. CONCLUSION: The 15-TF panel is an independent prognostic factor for HCC, and 15 TF-based nomogram might provide implication an effective approach for HCC patient management and treatment.

Silencing novel long non-coding RNA FKBP9P1 represses malignant progression and inhibits PI3K/AKT signaling of head and neck squamous cell carcinoma in vitro.

BACKGROUND: Long non-coding RNAs (lncRNAs) play key roles in human cancers. In our previous study, we demonstrated that lncRNA FKBP prolyl isomerase 9 pseudogene 1 (FKBP9P1) was highly expressed in head and neck squamous cell cancer (HNSCC) tissues. However, its functional significance remains poorly understood. In the present study, we identify the role and potential molecular biologic mechanisms of FKBP9P1 in HNSCC. METHODS: Quantitative real-time polymerase chain reaction was used to detect the expression of FKBP9P1 in HNSCC tissues, matched adjacent normal tissues, human HNSCC cells (FaDu, Cal-27, SCC4, and SCC9), and human immortalized keratinocytes cell HaCaT (normal control). Cal-27 and SCC9 cells were transfected with sh-FKBP9P1-1, sh-FKBP9P1-2, and normal control (sh-NC) lentivirus. Cell counting kit-8 assay, colony formation assay, wound healing assay, and trans-well assay were used to explore the biologic function of FKBP9P1 in HNSCC cells. Furthermore, western blotting was used to determine the mechanism of FKBP9P1 in HNSCC progression. Chi-squared test was performed to assess the clinical significance among FKBP9P1 high-expression and low-expression groups. Survival analyses were performed using the Kaplan-Meier method and assessed using the log-rank test. The comparison between two groups was analyzed by Student t test, and comparisons among multiple samples were performed by one-way analysis of variance and a Bonferroni post hoc test. RESULTS: FKBP9P1 expression was significantly up-regulated in HNSCC tissues (tumor vs. normal, 1.914 vs. 0.957, t = 7.746, P < 0.001) and cell lines (P < 0.01 in all HNSCC cell lines). Besides, the median FKBP9P1 expression of HNSCC tissues (1.677) was considered as the threshold. High FKBP9P1 level was correlated with advanced T stage (P = 0.022), advanced N stage (P = 0.036), advanced clinical stage (P = 0.018), and poor prognosis of HNSCC patients (overall survival, P = 0.002 and disease-free survival, P < 0.001). Knockdown of FKBP9P1 led to marked repression in proliferation, migration, and invasion of HNSCC cells in vitro (P all < 0.01). Mechanistically, silencing FKBP9P1 was observed to restrain the PI3K/AKT signaling pathway. CONCLUSIONS: Silencing lncRNA FKBP9P1 represses HNSCC progression and inhibits PI3K/AKT (phosphatidylinositol 3 kinase/AKT Serine/Threonine Kinase) signaling in vitro. Therefore, FKBP9P1 could be a potential new target for the diagnosis and treatment of HNSCC patients.

The impact of lung protective ventilation strategy on elderly emergency surgical patients / 中国现代医生

Objective To observe the effects of implementing lung protective ventilation strategies on lung dynamic compliance and oxygenation function in elderly emergency surgery patients.Methods A total of 126 elderly patients undergoing emergency surgery admitted to Northern Jiangsu People's Hospital from December 2021 to December 2022 were selected.They were randomly divided into an observation group and a control group,with 63 patients in each group,using a random number table method.All selected cases underwent general anesthesia mechanical ventilation during surgery.The control group chose conventional ventilation mode,while the observation group adopted lung protective ventilation.The lung dynamic compliance,oxygenation function,inflammatory indicators,and complications of the two groups of patients were compared.Results Within 30 minutes of surgery,the mean airway pressure(Pmean)and peak airway pressure(Ppeak)levels of both groups of patients increased compared to preoperative levels.The observation group had a smaller increase than the control group(P<0.05),and the pulmonary dynamic compliance(Cdyn)levels were lower than preoperative levels.The observation group had a lower increase than the control group(P<0.05).After 2 hours of surgery,the levels of Pmean and Ppeak in both groups of patients decreased compared to 30 minutes during surgery,and the decrease in the observation group was smaller than that in the control group(P<0.05).The levels of Cdyn in both groups decreased compared to before surgery,and the observation group was lower than that in the control group(P<0.05).24 hours after surgery,the blood oxygen saturation(SpO2)and arterialpartial pressure of oxygen(PaO2)levels in both groups of patients decreased compared to before surgery,and the observation group was lower than the control group(P<0.05).The alveolar-arterial oxygen partial pressure difference[P(A-a)DO2]levels between the two groups increased compared to preoperative levels,and the observation group was higher than the control group(P<0.05).48 hours after surgery,the SpO2 and PaO2 levels in the observation group were higher than those in the control group,and the P(A-a)DO2 levels were lower than those in the control group(P<0.05).24 hours after surgery,the serum C-reactive protein(CRP)and white blood cell(WBC)levels in both groups were significantly increased compared to preoperative levels,and the observation group was higher than those in the control group(P<0.05).48 hours after surgery,the serum CRP and WBC levels of both groups of patients decreased compared to 24 hours after surgery,and the observation group was lower than the control group(P<0.05).The incidence of complications in the observation group was lower than that in the control group(7.94％vs.25.40％)(P<0.05).Conclusion Implementing lung protective ventilation strategies for elderly emergency surgical patients is beneficial for improving lung dynamic compliance and oxygenation function,inhibiting the release of inflammatory cytokines,reducing the incidence of postoperative pulmonary complications,and effectively exerting lung protective effects.

Effect of individualized PEEP titration based on open-lung strategy on intraoperative thoracic fluid content in elderly patients undergoing transurethral ultrasound-guided laser-induced prostatectomy / 中华麻醉学杂志

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.

The characteristic of an anti-human DR5 antibody A6.

The efficacy of many cancer treatments is due to their ability to induce apoptosis. DR5 can activate apoptosis pathway after binding with its natural ligand, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L). Both TRAIL and agonistic anti-DR5 monoclonal antibody are currently being explored for cancer therapy. The mechanisms of cytotoxicity of our previously prepared monoclonal antibody A6 against DR5 were investigated here. A6 could cause viability loss of Jurkat cells in both time- and dose-dependent manner which could be attributed to the activation of apoptosis pathway. Caspases 3, 8 and 9 were activated in Jurkat cells and the caspase specific inhibitors, such as broad caspases inhibitor Z-VAD-FMK, caspase 8 specific inhibitor Z-IETD-FMK and caspase 9 specific inhibitor Z-LEHD-FMK could recover the viability loss caused by A6. The function and molecular mechanism of TRAIL-mediated apoptosis were also investigated and compared with those of A6. Although A6 and TRAIL recognize a different epitope, they could induce a similar reaction in Jurkat cells.

[Video-assisted thoracoscopic extended thymectomy for myasthenia gravis].

OBJECTIVE: To investigate the outcome of video-assisted thoracoscopic extended thymectomy (VATET) for myasthenia gravis. METHODS: From January 2005 to February 2006, VATET had been performed for 41 patients of myasthenia gravis. Among them, 23 patients were female and 18 were male. The age ranged from 18 to 67 years old, and the disease duration ranged from 1 month to 3 years. In order to achieve maximal benefit, a transverse cervical incision was given access to the peri-thyroid space to remove fat in the neck which may contain ectopic thymus after all thymic tissue, including far-reaching ectopic sites. Peri-thymic adipose tissue in the anterior mediastinum was completely removed. RESULTS: In the 41 patients, mean operative time was 162 min. Sever patients sustained myasthenic crises that required reintubation and mechanical ventilation for a few days. Of all patients, 35 had lymphadenectasis, and 4 had ectopic thymus in the peri-thyroid space. After the 2 years' follow-up, the rate of complete stable remission was 41.4%, and the effective rate was 85.4%. CONCLUSIONS: Video-assisted thoracoscopic thymectomy represents a safe and valid approach for patients with myasthenia gravis. VATET may be a complement to completely remove all thymus including ectopic tissues.

Risk factor for prolonged post-anesthesia care unit stay in elderly patients after painless gastrointestinal endoscopy / 中华麻醉学杂志

Objective:To identify the risk factor for prolonged post-anesthesia care unit (PACU) stay in elderly patients after painless gastrointestinal endoscopy.Methods:The elderly patients received painless gastrointestinal endoscopy from March to June 2021 in our hospital were included in this study. The information such as preoperative interview, patient′s general condition, current and past medical history, intraoperative conditions, and conditions in the PACU was collected. Patients were divided into non-prolonged group (group N) and prolonged group (group D) based on whether PACU stay was prolonged, and the risk factors for prolonged PACU stay were identified by logistic regression analysis.Results:There were 257 patients in group D and 716 cases in group N, and the incidence of prolonged PACU stay was 26.4%. Compared with group N, the proportion of preoperative frailty, smoking, intraoperative hypotension, and ratio of hypotension, somnolence and dizziness in PACU were significantly increased in group D ( P<0.05). The results of logistic regression analysis showed that preoperative frailty, smoking, intraoperative hypotension, and hypotension, somnolence and dizziness in PACU were independent risk factors for prolonged PACU stay( P<0.05). Conclusions:Preoperative frailty, smoking, intraoperative hypotension, and hypotension, somnolence and dizziness are independent risk factors for prolonged PACU stay in elderly patients after painless gastrointestinal endoscopy.

Effect of transcutaneous electrical acupoint stimulation with midnight-noon ebb-flow acupoint selection on postoperative delirium in patients undergoing radical resection of colorectal cancer / 中华麻醉学杂志

Objective:To evaluate the effect of transcutaneous electrical acupoint stimulation with midnight-noon ebb-flow acupoint selection on postoperative delirium (POD) in the patients undergoing radical resection of colorectal cancer.Methods:A total of 93 patients of either sex, aged ≥18 yr, with body mass index <30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱor Ⅲ, scheduled for elective radical resection of colorectal cancer under general anesthesia, were divided into 3 groups ( n=31 each) using a random number table method: control group (group C), common TEAS group (group CT), and midnight-noon ebb-flow acupoint selection TEAS group (group MT). The patients received TEAS at bilateral Hegu, Quchi and Shousanli acupoints at 6: 00 in group MT and at 18: 00 in group CT on the day of operation and 1-3 days after surgery, with a frequency of 2/100 Hz, disperse-dense waves, intensity the maximum current that could be tolerated, and each TEAS lasted for 30 min. In group C, only the electrodes were pasted at the same acupoints without electric current at 6: 00 am. The POD was evaluated by the Confusion Assessment Method (CAM) at 1, 3 and 5 days after operation (T 1-3). Blood samples were collected for determination of serum interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) concentrations at 1 day before operation and at T 1. The time to first flatus and defection and adverse reactions after operation were recorded. Results:Compared with group C, the CAM scores at each time point and incidence of POD were significantly decreased, the concentrations of IL-1β, TNF-a and IL-6 in serum were decreased at T 1, the time to the first flatus and defecation was shortened, and the incidence of abdominal distension after surgery was decreased in MT and CT groups ( P<0.05). Compared with group CT, the CAM scores at T 3 and incidence of POD were significantly decreased, the concentrations of TNF-a and IL-6 at T 1 were decreased, and the time to first defecation after operation was shortened in group MT ( P<0.05). Conclusions:TEAS guided by midnight-noon ebb-flow acupoint selection provides better efficacy than common TEAS in decreasing the risk of POD in the patients undergoing radical resection of colorectal cancer, which is helpful for the early postoperative recovery of patients.

Development and validation of a predictive model for PACU hypotension in elderly patients undergoing painless gastrointestinal endoscopy / 中华麻醉学杂志

Objective:To develop and validate a predictive model for post-anesthesia care unit (PACU) hypotension in elderly patients undergoing painless gastrointestinal endoscopy.Methods:The medical records of elderly patients of both sexes, aged ≥60 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, undergoing painless gastrointestinal endoscopy at the Endoscopy Center of Subei People′s Hospital from March to June 2021, were retrospectively collected. The patients were randomly divided into training and validation sets according to the ratio of 3∶1. In the training set, the characteristic variables associated with PACU hypotension were screened by Lasso regression, and the independent risk factors for PACU hypotension were identified by multivariate logistic regression analysis of the characteristic variables, according to which a nomogram model predicting the risk for PACU hypotension was established.The discrimination, calibration and accuracy of the model were evaluated by calibration curve and receiver operating characteristic(ROC)curve. And the clinical practicability of the model was determined by decision curve analysis and further assessed by external validation.Results:Of the 973 patients ultimately included, 378 patients experienced PACU hypotension, with an incidence of 38.8%. Multivariate logistic regression analysis showed that age, prolonged preoperative water deprivation time, increased percentage of changes in SBP before and after induction, and intraoperative MAP <65 mmHg were independent risk factors for hypotension in the PACU, and intraoperative use of norepinephrine was a protective factor. The nomogram model was then developed based on the results. The area under the ROC curve was 0.710 (95% confidence interval [ CI] 0.672-0.748) in training set and 0.778 (95% CI 0.720-0.837) in validation set. In training and validation sets, the calibration curves were tested by Hosmer-Lemeshow good of fit test, the P values were 0.590 and 0.950, respectively. The decision curve analysis curve showed that the risk threshold of the prediction model in the training and validation sets were between 20% and 82% and between 18% and 92%, respectively, in the external validation. Conclusions:The nomogram model for prediction of PACU hypotension is successfully established based on age, prolonged preoperative water deprivation, percentage of change in SBP before and after induction, intraoperative MAP <65 mmHg and use of norepinephrine in elderly patients undergoing painless gastrointestinal endoscopy, and the model can visually and individually predict the risk of PACU hypotension.

Effects of lung protective ventilation on brain function in patients with traumatic brain injury / 中华急诊医学杂志

Objective:To evaluate the effect of individualized positive end-expiratory pressure (PEEP) ventilation strategy guided by driving pressure on intraoperative intracranial pressure in patients with moderate traumatic brain injury (TBI).Methods:Total of 111 patients aged 18-65 years old, with BMI of 17-28 kg/m 2, ASA grade of Ⅲ-Ⅳ, and Glasgow coma score of 9-11 before operation were treated with evacuation of intracranial hematoma in emergency. The patients were randomly divided into 0 cmH 2O PEEP group (Group 0 PEEP), 5 cmH 2O PEEP group (Group 5 PEEP) and individualized PEEP ventilation group (Group P) guided by driving pressure. The volume control ventilation mode is adopted, VT is 6 mL/kg, FiO 2 is 60%, and the inspiratory expiratory ratio is 1:2. Patients in Group 0 PEEP and Group 5 PEEP were given PEEP 0 or 5 cmH 2O for ventilation after tracheal intubation until the end of the operation. Patients in Group P were given individualized PEEP titration ventilation strategy guided by driving pressure after intubation. Blood gas analysis was performed at 5 min (T1) after tracheal intubation, 60 min (T3) after operation, and 5 min (T4) after operation. PaO 2, PaCO 2, and dynamic compliance (Cdyn) were recorded. The optic nerve sheath diameter (ONSD) was measured before anesthesia induction (T0), after PEEP titration in group P (T2, 10 min after ventilation in group 0 PEEP and 5 PEEP) and at T4; Serum neuron specific enolase (NSE) concentration was measured by ELISA before and 1 day and 3 days after operation; The occurrence of nervous system complications (intracranial infection, intracranial hypertension, epilepsy, brain edema, etc.) within 30 days after operation was followed up. Results:Compared with group 0 PEEP and 5 PEEP, Cdyn and PaO 2 in group P increased at T3-4 ( P<0.05), ONSD was not significantly different among the three groups ( P>0.05), NSE in group P decreased significantly at 1 and 3 days after operation, and the incidence of neurological complications in the three groups was not significantly different at 30 days after operation ( P>0.05). Conclusions:Individualized PEEP ventilation strategy guided by driving pressure can help improve lung and brain function in TBI patients.

Effect of ventilator-induced lung injury on blood-brain barrier permeability in rats / 中华危重病急救医学

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.

Effects of open-lung strategy on postoperative delirium in elderly patients undergoing laparoscopic surgery / 中华麻醉学杂志

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.

Gastric emptying in patients with cholelithiasis and in patients following cholecystectomy: measurement by ultrasonography / 中华麻醉学杂志

Objective:To evaluate the gastric emptying in the patients with cholelithiasis and in the patients following cholecystectomy by ultrasonography.Methods:Thirty patients with cholelithiasis, 30 post-cholecystectomy patients and 30 healthy volunteers, of either sex, aged 18-64 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰor Ⅱ, were selected and divided into cholelithiasis group (group CH), post-cholecystectomy group (group PC) and healthy volunteer group (group HV). The indigestion scores of the enrolled subjects in the past 3 months were assessed; the subjects took a semi-solid test meal (300 kcal) in the fasting state, and the cross-sectional area (CSA) of the gastric sinus was measured using ultrasound at fasting (T 0) and 5, 15, 30, 45, 60, 90 and 120 min after the test meal was taken (T 1-7). The gastric emptying fraction at T 5, 6 was calculated. The gastric half-emptying time and remaining area of the gastric sinus at T 7 were also calculated. Results:Compared with group HV, dyspepsia scores were significantly increased within the past 3 months ( P<0.05), the CSA of the gastric sinus was increased at T 3-7, the gastric emptying fraction was decreased at T 5-6, the gastric half-emptying time was prolonged, and the remaining area of the gastric sinus was increased at T 7 in group CH and group PC ( P<0.05). Compared with group CH, the CSA of the gastric sinus was significantly increased at T 4-7, the gastric emptying fraction was decreased at T 5, 6, the gastric half-emptying time was prolonged, and the remaining area of the gastric sinus was increased at T 7 in group PC ( P<0.05). Conclusions:Gastric emptying time is longer in the patients with cholelithiasis and in the patients following cholecystectomy than in healthy subjects and is further prolonged after cholecystectomy in the patients.

Relationship between SIRT1 and ferroptosis during curcumin-induced reduction of acute lung injury in a mouse model of sepsis / 中华麻醉学杂志

Objective:To evaluate the relationship between silent information regulator 1 (SIRT1) and ferroptosis during curcumin-induced reduction of acute lung injury in a mouse model of sepsis.Methods:One hundred and fifty-two SPF-grade male C57BL/6J mice, aged 8 weeks, weighing 23-27 g, were divided into 4 groups ( n=38 each) using a random number table method: sham operation group (C group), sepsis group (S group), curcumin group (Cur group) and curcumin plus SIRT1 inhibitor EX527 group (CE group). Curcumin 200 mg/kg was administered by intragastric gavage every day in Cur group. Curcumin 200 mg/kg was administered by intragastric gavage every day and EX527 5 mg/kg was intraperitoneally injected in CE group. The equal volume of solvent dimethyl sulfoxide (DMSO) was given in C group and S group. Sepsis model was developed by cecal ligation and puncture (CLP) after 5 days of consecutive administration in anesthetized animals. Twenty mice in each group were randomly selected to observe the survival condition within 7 days after CLP. The bronchoalveolar lavage fluid (BALF) was collected at 24 h after developing the model to determine the concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), IL-6 and IL-18 (by enzyme-linked immunosorbent assay), and the lung tissues were obtained for microscopic examination of the pathological changes which were scored and for determination of wet-to-dry lung weight (W/D) ratio, contents of glutathione (GSH), malondialdehyde (MDA) and iron (by colorimetry), and expression of SIRT1, glutathione peroxidase 4 (GPX4) and Acyl-CoA synthetase long chain family member 4 (ACSL4) (by Western blot). Results:Compared with C group, the 7-day survival rate after CLP was significantly decreased, the concentrations of TNF-α, IL-1β, IL-6 and IL-18 in BALF, W/D ratio and lung injury score were increased, the content of GSH in lung tissues was decreased, the contents of MDA and iron were increased, the expression of SIRT1 and GPX4 was down-regulated, and the expression of ACSL4 was up-regulated in S group ( P<0.05). Compared with S group, the 7-day survival rate after CLP was significantly increased, the concentrations of TNF-α, IL-1β, IL-6 and IL-18 in BALF, W/D ratio and lung injury score were decreased, the content of GSH was increased, the contents of MDA and iron were decreased, the expression of SIRT1 and GPX4 was up-regulated, and the expression of ACSL4 was down-regulated in Cur group ( P<0.05). Compared with Cur group, the 7-day survival rate after CLP was significantly decreased, the concentrations of TNF-α, IL-1β, IL-6 and IL-18 in BALF, W/D ratio and lung injury score were increased, the content of GSH was decreased, the contents of MDA and iron were increased, the expression of SIRT1 and GPX4 was down-regulated, and the expression of ACSL4 was up-regulated in CE group ( P<0.05). Conclusions:The mechanism by which curcumin attenuates acute lung injury may be related to activation of SIRT1 and further inhibition of ferroptosis in mice.