Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Objective:To explore the effects of phased goal directed fluid therapy (GDFT) during anesthesia surgery on tissue perfusion and cognitive function in patients undergoing radical lung cancer surgery.Methods:A total of 108 lung cancer patients were prospectively selected and randomly divided into a control group and a study group using a random number table method. The control group received classical restrictive liquid therapy, while the study group received staged GDFT. We compared the surgical time, intraoperative blood loss, colloid fluid dosage, crystalloid fluid dosage, total output, and urine volume between two groups of patients; Two groups of patients were compared in terms of oxygenation index (OI), respiratory index (RI), central venous oxygen saturation (ScvO 2), lactate (Lac), central venous arterial carbon dioxide partial pressure difference (Pcv-aCO 2), oxygen supply index (DO 2I), and oxygen uptake rate (O 2ERe) before anesthesia induction (T 0), before single lung ventilation (T 1), 1 hour of single lung ventilation (T 2), immediate resumption of dual lung ventilation (T 3), 30 minutes of dual lung ventilation (T 4), and after surgery (T 5); The Mini Mental State Examination (MMSE) was used to evaluate the cognitive function scores of two groups of patients 1 day before surgery and 1 and 3 days after surgery, while recording the incidence of cognitive dysfunction (POCD) and pulmonary complications (including pulmonary infection, acute lung injury, pulmonary embolism, pulmonary edema, atelectasis, etc.) within 3 days after surgery. Results:The amount of crystal fluid and urine output in the research group was significantly lower than that in the control group, while the amount of colloidal fluid was significantly higher than that in the control group (all P<0.05). The OI of the study group T 1-T 5 was significantly higher than that of the control group, while the RI of T 2-T 5 was significantly lower than that of the control group (all P<0.05). The ScvO 2 of the study group T 1 to T 5 was significantly higher than that of the control group, and the Lac was significantly lower than that of the control group (all P<0.05); The MMSE scores of both groups of patients were significantly lower than those before surgery on day 1 and 3 after surgery, and the MMSE scores of the study group were significantly higher than those of the control group on day 1 and 3 after surgery (all P<0.05). The incidence of POCD within 3 days after surgery in the study group was 16.67%(9/54), lower than 37.04%(20/54) in the control group (χ 2=5.704, P=0.017); The incidence of pulmonary complications in the study group was lower than that in the control group (5.56% vs 22.22%, χ 2=4.955, P=0.026). Conclusions:The application of staged GDFT during anesthesia in patients undergoing radical lung cancer surgery can further improve tissue perfusion, improve microcirculation and oxygen supply-demand balance of systemic organs and tissues, including the brain, alleviate perioperative brain function damage, and reduce the occurrence of postoperative POCD compared to conventional liquid therapy.

Objective To compare the safety and clinical value of warm-water infusion or carbon dioxide(CO2)insufflation in difficult colonoscopy.Methods A collection of 150 patients from May 2021 to October 2023 who underwent unsedated and difficult colonoscopy were randomly divided into warm-water insufflation group(W group,n=50),CO2 insufflation group(C group,n=50)and air insufflation group(A group,n=50).Record the cecal insertion time,the abdominal pain score during the examination and 20 min and 1 h after the examination,the success rate of intubation,the polyps detection rate,the willingness to re-examine and the need for assistance in the three groups.Some patients were randomly selected to record partial pressure of end-tidal carbon dioxide(PetCO2)of pre-examination,the ileocecal and 20 min after the examination to understand CO2 retention in the body.Results The cecal insertion time of group A was longer than that of group W and group C,and group W was shorter than group C.The abdominal pain score of group A was higher than that of group W and group C at each time point,and the abdominal pain score during the examination was lower in the group W compared with group C.The success rate of intubation and the willingness to re-examination in the group A were lower than those in group W and group C,The above differences were statistically significant(P<0.05).However,there was no statistical difference between the the group W and group C in terms of success rate of intubation,willingness to re-examine,and abdominal pain score at 20 minutes and 1 hour after the examination(P>0.05).In the group W,significantly fewer patients required abdominal compression compared with the other two groups,and the rate of position conversion was significantly lower than that in group A(P<0.05).There was no significant difference in the detection rate of polyps among the three groups(P>0.05).In addition,PetCO2 of group C was within the normal range at all time points,and there was no statistical difference compared with the group A(P>0.05).Conclusion Compared with the air group,water or CO2 insufflation colonoscopy is safe and has a high success rate in difficult colonoscopy.It can reduce the patient's abdominal discomfort,especially water insufflation colonoscopy is more suitable for promotion in primary hospitals.

Objective:To explore the clinical and genetic characteristics of asparagine synthase deficiency.Methods:Case series studies. Retrospective analysis and summary of the clinical data of 6 cases with asparagine synthase deficiency who were diagnosed by genetic testing and admitted to the Third Affiliated Hospital of Zhengzhou University from May 2017 to April 2023 were analyzed retrospectively. The main clinical features, laboratory and imaging examination characteristics of the 6 cases were summarized, and the gene variation sites of them were analyzed.Results:All of the 6 cases were male, with onset ages ranging from 1 month to 1 year and 4 months. All of the 6 cases had cognitive and motor developmental delay, with 3 cases starting with developmental delay, 3 cases starting with convulsions and later experiencing developmental arrest or even regression. All of 6 cases had epilepsy, in whom 2 cases with severe microcephaly developed epileptic encephalopathy in the early stages of infancy with spasms as the main form of convulsions, 4 cases with mild or no microcephaly gradually evolved into convulsions with no fever after multiple febrile convulsions with focal seizures, tonic clonic seizures and tonic seizure as the main forms of convulsions. Three cases of 4 gradually developed into stagnation or even regression of development and ataxia after multiple convulsions with no fever. There were normal cranial imaging in 2 cases, dysplasia of the brains in 1 cases, frontal lobe apex accompanied by abnormal white matter signal in the frontal lobe and thin corpus callosum in 1 case, thin corpus callosum and abnormal lateral ventricular morphology in 1 case, and normal in early stage, but gradually developing into cerebellar atrophy at the age of 5 years and 9 months in 1 case. Two cases underwent visual evoked potential tests, the results of which were both abnormal. Three cases underwent auditory evoked potential examination, with 1 being normal and 2 being abnormal. All of 6 cases had variations in the asparagine synthase gene, with 2 deletion variations and 7 missense variations. The variations of 2 cases had not been reported so far, including c.1341_1343del and c.1283A>G, c.1165_1167del and c.1075G>A. The follow-up time ranged from 3 months to 53 months. Two cases who had severe microcephaly died in infancy, while the other 4 cases with mild or no microcephaly were in survival states until the follow-up days but the control of epilepsy was poor.Conclusions:Asparagine synthase deficiency has a certain degree of heterogeneity in clinical phenotype. Children with obvious microcephaly often present as severe cases, while children with mild or no microcephaly have relatively mild clinical manifestations. The variation of asparagine synthetase gene is mainly missense variation.

Objective:To evaluate the effect of ultrasound-guided single fascia iliaca compartmentblock (FICB) combined with esketamine on postoperative delirium (POD) in elderly patients undergoing hip fracture surgery.Methods:Sixty-two patients of either sex, aged 60-85 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing hip fracture surgery under subarachnoid anesthesia, were divided into 2 groups ( n=31 each) using a random number table method: single FICB group (group FICB) and single FICB combined with esketamine group (group FICB+ E). Ultrasound-guided FICB was performed on the operated side at 30 min before subarachnoid anesthesia. In FICB+ E group, esketamine was intravenously injected as a bolus of 0.3 mg/kg at 5 min before skin incision followed by an infusion of 0.25 mg·kg -1·h -1 until 30 min before the end of procedure. Patient-controlled intravenous analgesia was used for postoperative analgesia, and tramadol 1 mg/kg was given for rescue analgesia. The pressing times of patient-controlled analgesia, the number of rescue analgesia, and consumption of tramadol were recorded within 48 h after operation. The Ramsay sedation score was used to assess the degree of sedation at skin incision, 30 min after the start of surgery, 30 min before the end of surgery, at the end of surgery, and at discharge from the post-anesthesia care unit. Postoperative delirium (POD) occurred within 7 days after surgery was assessed using the Confusion Assessment Method. The serum concentrations of tumor necrosis factor-alpha, interleukin-6, S100β and glial fibrillary acidic protein (GFAP) were detected by enzyme-linked immunosorbent assay on admission to the operating room and at 3 and 7 days after surgery. The occurrence of adverse drug reactions (respiratory depression, nausea and vomiting, dizziness, somnolence, urinary retention) was recorded. Results:Compared with group FICB, the incidence of POD was significantly decreased within 3 days after surgery, the consumption of tramadol, pressing times of patient-controlled analgesia and the number of rescue analgesia were reduced, Ramsay sedation score was increased at each time point, and the serum concentrations of tumor necrosis factor-alpha, interleukin-6, S100β and glial fibrillary acidic protein were decreased after surgery ( P<0.05), and no significant change was found in the total incidence of POD at 7 days after surgery in group FICB+ B ( P>0.05). Conclusions:Ultrasound-guided single FICB combined with esketamine can provide adequate analgesia and sedation in the perioperative period for elderly patients with hip fractures, reducing the risk of early postoperative (within 3 days) POD.

Objective:To evaluate the efficacy of esketamine combined with fascia iliaca compartment-subarachnoid block in optimizing anesthesia in elderly patients undergoing hip fracture surgery.Methods:Sixty-two American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ elderly patients of either sex, aged 60-85 yr, with body mass index of 18.5-30.0 kg/m 2, were divided into 2 groups ( n=31 each) using a random number table method: fascia iliaca compartment-subarachnoid block group (FS group) and esketamine combined with fascia iliaca compartment-subarachnoid block group (ES group). In FS group, patients underwent ultrasound-guided fascia iliaca compartment block at 30 min before the operation of subarachnoid anesthesia on the surgical side. In ES group, esketamine 0.25 mg/kg was intravenously administered at 5 min before skin incision based on the fascia iliaca compartment-subarachnoid block. Patient-controlled intravenous analgesia was used for postoperative analgesia, and tramadol 1 mg/kg was intravenously given for rescue analgesia when numerical rating scale score > 4. The pressing times of patient-controlled analgesic pump, the number of rescue analgesia and consumption of tramadol were recorded within 48 h after operation. The occurrence of postoperative adverse reactions (respiratory depression, nausea and vomiting, dizziness, drowsiness, pruritus, illusion, nightmares) was recorded. Results:Compared with FS group, the consumption of postoperative tramadol was significantly decreased, and the pressing times of patient-controlled analgesic pump and the number of rescue analgesia were reduced in ES group ( P<0.05). There were no significant differences in the incidence of postoperative adverse reactions between the two groups ( P>0.05). Conclusions:Combination of esketamine with fascia iliaca compartment-subarachnoid block for hip fracture surgery can raise postoperative analgesia and optimize clinical management strategies in elderly patients.

Objective:To evaluate the role of stimulator of interferon genes (STING) signaling pathway in carbon monoxide (CO)-releasing molecule-3 (CORM-3)-induced reduction of hepatocyte pyroptosis and apoptosis in a rat model of hepatic ischemia-reperfusion.Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 9-11 weeks, weighing 320-380 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (S group), ischemia-reperfusion group (IR group), CORM-3 group (C group) and STING agonist ADU-S100 group (A group).Hepatic ischemia-reperfusion injury models were developed by reversible ligation of left middle hepatic artery, portal vein and bile duct branches for 45 min, followed by reperfusion in anesthetized animals in IR, C and A groups.In group C, CORM-3 4 mg/kg was injected into the femoral vein immediately after reperfusion.The equal volume of normal saline containing dimethyl sulfoxide was injected into the femoral vein in S, IR and A groups.At 1.5 h after injection into the femoral vein, ADU-S100 10 mg/kg was intraperitoneally injected in A group, and the equal volume of normal saline was given instead in S, IR and C groups.The serum alanine transaminase (ALT) and aspartate transaminase (AST) concentrations were determined at 3 h of reperfusion.The rats were sacrificed at 12 h of reperfusion, and liver tissues were collected for determination of the content of CO (by colorimetry), expression of interleukin-1beta (IL-1β), IL-18, Bcl-2, Bax, interferon regulatory factor 3 (IRF3), phosphorylated IRF3 (p-IRF3), STING, NOD-like receptor protein 3 (NLRP3), aspirin D (GSDMD) and activated caspase-1 (by Western blot), and pyroptosis and apoptosis rates of hepatocytes (by immunofluorescence staining).The liver injury was scored. Results:Compared with group S, the serum ALT and AST concentrations, liver injury score, CO content, and pyroptosis and apoptosis rates of hepatocytes were significantly increased, and the expression of IL-1β, IL-18, p-IRF3, STING, NLRP3, GSDMD and activated caspase-1 was up-regulated, and the Bcl-2/Bax ratio was decreased in group IR ( P<0.05).Compared with group IR, the serum ALT and AST concentrations, liver injury score, and pyroptosis and apoptosis rates of hepatocytes were significantly decreased, the CO content was increased, the expression of IL-1β, IL-18, p-IRF3, STING, NLRP3, GSDMD and activated caspase-1 was down-regulated, and the Bcl-2/Bax ratio was increased in group C ( P<0.05).Compared with group C, the serum ALT and AST concentrations, liver injury score, and pyroptosis and apoptosis rates of hepatocytes were significantly increased, the CO content was decreased, the expression of IL-1β, IL-18, p-IRF3, STING, NLRP3, GSDMD and activated caspase-1 was up-regulated, and the Bcl-2/Bax ratio was decreased in group A ( P<0.05). Conclusions:The mechanism by which CORM-3 attenuates hepatocyte pyroptosis and apoptosis may be related to the inhibition of activation of STING signaling pathway in a rat model of hepatic ischemia-reperfusion.

Objective: To investigate the changes and clinical significance of Caveolin-1, matrix metalloproteinase-9(MMP-9) and interleukin-1β(IL-1β)in cerebrospinal fluid of children with bacterial meningitis or viral encephalitis. Methods: Thirty-six cases of children with bacterial meningitis, 42 cases of children with viral encephalitis, and 20 cases of children with non-nervous system infection were selected from September 2016 to June 2018 at the Third Affiliated Hospital of Zhengzhou University.The levels of Caveolin-1, MMP-9 and IL-1β in cerebrospinal fluid were detected by using enzyme linked immunosorbent assay(ELISA). Results: Cerebrospinal fluid Caveolin-1, MMP-9 , IL-1β levels in the acute phase of bacterial meningitis were(49.06±8.96) ng/L, (134.79±18.88) μg/L, (100.02±14.67) μg/L, respectively, and (29.13±7.25) ng/L, (18.69±7.23) μg/L, (47.57±8.95) μg/L in recovery phase, which were higher than those of the controls[(11.18±2.24) ng/L, (11.53±3.54) μg/L, (39.75±7.08) μg/L)], and the differences were significant (all P<0.05). Cerebrospinal fluid Caveolin-1, MMP-9, IL-1β levels in the acute phase of viral encephalitis were (42.71±10.48) ng/L, (62.78±17.39) μg/L, (57.97±11.28) μg/L, respectively, and (29.13±7.25) ng/L, (18.69±7.23) μg/L, (47.57±8.95) μg/L in recovery phase, which were higher than those of controls, and the differences were significant (all P<0.05). The levels of Caveolin-1, MMP-9 and IL-1β in cerebrospinal fluid of bacterial meningitis group and viral encephalitis group were significantly higher than those of convalescent group (all P<0.05). The levels of Caveolin-1, MMP-9, IL-1β in cerebrospinal fluid of bacterial meningitis group were significantly higher than those in viral encephalitis group (all P<0.05) in the acute phase, and no significant difference was found in the recovery phase(all P>0.05). Cerebrospinal fluid Caveolin-1, MMP-9, IL-1β showed no significant difference among children with different severity of intracranial infection.Correlation analysis showed that there was a positive correlation between Caveolin-1, MMP-9 and IL-1 β levels in cerebrospinal fluid of acute in bacterial meningitis group and viral encephalitis group(Caveolin-1 and MMP-9: R²=0.239, P<0.05; MMP-9 and IL-1β: R²=0.766, P<0.01; Caveolin-1 and IL-1β: R²=0.245, P<0.05). Conclusions Caveolin-1, MMP-9 and IL-1 β involved in the pathogenesis of intracranial infection in children, and the effects of different pathogens on intracranial infection were different.

Objective: To investigate the changes and clinical significance of vascular endothelial (VE)-cadherin and procalcitonin (PCT) in serum and cerebrospinal fluid (CSF) of children with viral encephalitis or bacterial meningitis(BM). Methods: A total of 42 cases of children with viral encephalitis(viral encephalitis group), 36 cases of children with BM(BM group), and 20 cases of children with non-nervous system injury(control group) were selected from September 2016 to June 2018 at the Third Hospital of Zhengzhou University.The serum and CSF levels of VE-cadherin and PCT levels of the 3 groups were detected by using enzyme-linked immunosorbent assay. Results: The levels of VE-cadherin in the serum of viral encephalitis group, BM group and control group at the acute phase were (5.60±1.17) mg/L, (7.08±1.01) mg/L and (2.52±0.68) mg/L respectively, and the levels of VE-cadherin in CSF of viral encephalitis group, BM group and control group were (6.00±1.09) mg/L, (6.97±1.11) mg/L and(1.93±0.88) mg/L, respectively.The levels of PCT in the serum of viral encephalitis group, BM group and control group at the acute phase were (0.26±0.11) μg/L, (0.82±0.17) μg/L and (0.27±0.13) μg/L, respectively, and the levels of PCT in the CSF of viral encephalitis group, BM group and control group were (0.25±0.11) μg/L, (0.72±0.14) μg/L, (0.28±0.17) μg/L, respectively.As a result, the levels of VE-cadherin and PCT in the serum and CSF of BM group showed significant increase, compared with viral encephalitis group and control group in the acute phase(F=124.94, 163.21, 151.62, 127.37, all P<0.01). The levels of VE-cadherin in the serum and CSF of viral encephalitis group were also significantly higher than that of control group (all P<0.01), but there was no difference between viral encephalitis group and control group about the levels of PCT in the serum and CSF (all P>0.05). The levels of VE-cadherin in the serum of viral encephalitis group and BM group after treatment were (2.34±0.81) mg/L and (2.67±1.29) mg/L, and were(2.55±0.92) mg/L and(2.39±0.74) mg/L in the CSF.The levels of PCT in the serum of viral encephalitis group and BM group after treatment were (0.25±0.11) μg/L, (0.30±0.17) μg/L, and the levels of PCT in the CSF of viral encephalitis group and BM group were(0.22±0.10) μg/L and (0.27±0.12) μg/L.After effective treatment, the levels of VE-cadherin, PCT in serum and CSF of BM group and viral encephalitis group were almost equal, and the difference was not statistically significant(F=1.83, 0.76, 2.72, 3.89, all P>0.05). In the receiver operating characteristic (ROC) curve, the area under the ROC curve of VE-cadherin in serum and CSF was 0.896 and 0.912, and was 0.670 and 0.668 of PCT respectively. Conclusions VE-cadherin may be involved in the early stage of intracranial infection, and it may be helpful in differentiation of virus or bacterial infection with PCT.VE-cadherin has a good diagnostic value for intracranial infection.