ObjectiveTo identify the characteristic exhaled volatile organic compounds （VOCs） associated with postoperative pulmonary complications （PPCs） in patients after abdominal surgery. MethodsThis study prospectively enrolled 76 patients with tracheal intubation who were transferred to intensive care unit （ICU） after abdominal surgery at Peking University People's Hospital between December 10， 2022 and June 30， 2023. The patients' basic information was collected during their perioperative period， and their exhaled VOCs were collected within 24 hours after their admission to the ICU， and then analyzed by gas chromatography and mass spectrometry （GC-MS）. According to whether PPCs occurred 24 hours after surgery， the patients were divided into PPCs group （n=44） and non-PPCs group （n=32）， and the differences of VOCs were compared between the two groups. Lasso regression analysis was used to screen the valuable variables of VOCs， and Logistics regression analysis to determine the characteristic VOCs associated with the occurrence of PPCs. ResultsAmong the 76 patients， 44 had PPCs and 32 had no PPCs. Lasso regression analysis screened 4 PPCs-related compounds from exhaled VOCs of two groups for further analysis and Logistics regression analysis showed that the increase of 1-Hexadecanol content in exhaled breath was significantly correlated with the occurrence of PPCs （OR： 1.000， P=0.002）. ConclusionThis study indicated that the increased content of 1-Hexadecanol in patients' exhaled breath after abdominal surgery may be associated with the occurrence of PPCs.

Objective:To evaluate the role of tubulin tyrosin ligase like-6 (TTLL6)-mediated microtubule polyglutamylation and Spastin(a microtubule cleaving protein)-induced excessive microtubule cleavage in the developmental impairment of dendritic spines in neonatal mice following repeated sevoflurane anesthesia, by utilizing TTLL6 conditional knockout mice.Methods:Fifty SPF female TTLL6 brain tissue-specific knockout (TTLL6 CKO: Camk2-Cre + ; TTLL6 f/f) and fifty control (TTLL6 CON: TTLL6 f/f) mice with C57BL/6J background, aged 6 days old were selected.TTLL6 CKO mice were divided into TTLL6 CON control group and TTLL6 CON sevoflurane group, and TTLL6 CKO mice were divided into TTLL6 CKO control group and TTLL6 CKO sevoflurane group, with 25 mice in each group by random block method.Mice in the sevoflurane groups were exposed to 3% sevoflurane with 60% O 2 for 2 hours daily on postnatal days 6, 8, and 10.The mice in control groups received only 60% O 2 under the same condition.The polyGlu-Tubulin and postsynaptic density 95(PSD95) protein expression were detected using Western blot. The expressions of TTLL6, Spastin, and α-Tubulin were assessed via immunofluorescence.Golgi staining and electron microscopy were employed to observe the density of hippocampal dendritic spines and synaptic conditions. The Morris water maze test was used to evaluate spatial memory capabilities. Statistical analysis was performed using GraphPad Prism 8.0 software. Results:(1) Behavioral results showed significant time and group interactions among the four groups in terms of latency to find the platform ( F=8.22, P<0.001).Mice in the TTLL6 CON sevoflurane group had a significantly longer escape latency on days 3-7 compared with the TTLL6 CON control group (all P<0.05), while there was no significant difference between the TTLL6 CKO sevoflurane group and the TTLL6 CKO control group (all P>0.05). The number of platform crossings differed significantly among the four groups ( H=11.95, P=0.007).The TTLL6 CON sevoflurane group had significantly fewer crossing times than the TTLL6 CON control group ( P<0.05), but no significant difference was observed between the TTLL6 CKO sevoflurane group and the TTLL6 CKO control group ( P>0.05). (2) Golgi staining and electron microscopy results revealed significant differences in dendritic spine density and synapse number among the four groups( F=29.00, 41.94, both P<0.001). The dendritic spine density ((5.83±0.40)/10 μm) and the number of synapses ((3.67±0.58)/10 μm) in the TTLL6 CON sevoflurane group were both significantly lower than those in the TTLL6 CON control group ((12.87±1.70)/10 μm, (9.33±0.57)/10 μm)(both P<0.05). In contrast, there was no statistically significant difference between the TTLL6 CKO sevoflurane group and TTLL6 CKO control group (both P>0.05). (3) Immunofluorescence results showed significant differences in the percentage of TTLL6 and Spastin and α-Tubulin co-expressed positive cells in the CA3 region of the hippocampus among the four groups of mice ( F=215.20, 26.08, both P<0.001). The percentage of TTLL6 and Spastin and α-Tubulin co-expressed positive cells in the TTLL6 CON sevoflurane group ((16.75±1.81) %, (47.98±8.42) %) were significantly higher than those in the TTLL6 CON control group ((2.44±0.58) %, (20.07±4.54) %)(both P<0.05), while there was no statistically significant difference between the TTLL6 CKO sevoflurane group and TTLL6 CKO control group ( P>0.05). (4) Western blot results indicated significant differences in the expression of polyGlu-Tubulin and PSD95 proteins in the hippocampal tissue among the four groups of mice ( F=19.66, 8.57, both P<0.001). The TTLL6 CON sevoflurane group had higher polyGlu-Tubulin expression (0.86±0.19) and lower PSD95 expression (0.61±0.13) compared to the TTLL6 CON control group (0.51±0.11, 1.01±0.07) (both P<0.05).However, there was no significant difference between the TTLL6 CKO sevoflurane group and the TTLL6 CKO control group ( P>0.05). Conclusion:The mechanism underlying long-term cognitive impairment in developing brain of neonatal mice caused by repeated sevoflurane anesthesia may relate to the upregulation of TTLL6-induced microtubule polyglutamylation and accelerated Spastin-mediated microtubule severing, which ultimately leads to abnormal dendritic spine development.

Objective To explore the application of artificial intelligence quantitative analysis in the prognostic assessment of patients with connective tissue disease-associated interstitial lung disease(CTD-ILD).Methods A total of 67 patients with CTD-ILD were retrospectively selected.All subjects underwent high-resolution computed tomography(HRCT)scanning and were categorized into three groups,namely mild,moderate and severe groups,based on the results of pulmonary function tests.The survival rates of patients in each group were compared using Kaplan-Meier curves and analysis of variance.The univariate analysis was employed to assess the rela-tionships between artificial intelligence parameters and patient prognosis.Significant results were then incorporated into a multifacto-rial Cox regression model to construct the most accurate predictive model.Results A significant difference in survival rate was observed among the three groups(P<0.05).Univariate analysis revealed that the volume and percentage of lung infection in deceased patients were significantly greater than those in surviving patients,while the lung volume in deceased patients was significantly smaller than that in surviving patients.The analysis showed left lung volume and the percentage of lesion components CT value≤-750 HU as risk factors for prognosis,and the combination of these two factors as the most effective predictive model.Conclusion The artificial intelligence analysis system for lung lesions provides a new systematic and quantitative method for the prognostic assessment of CTD-ILD patients,which can be used for the prognostic assessment and follow-up of CTD-ILD patients.

Objective To investigate the association between gut microbiota metabolite,trimethy-lamine-N-oxide(TMAO),and total imaging burden in diabetic patients with cerebral small vessel disease(CSVD).Methods A prospective study was conducted on 112 elderly diabetic patients with CSVD admitted in our hospital from June 2022 to May 2024.According to the total imaging burden score,they were divided into a high burden group(burden score≥2,57 cases)and a low burden group(burden score＜2,55 cases).High-performance liquid chromatography with online electrospray ionization tandem mass spectrometry was applied to detect the plasma level of TMAO.Then based on the tertile of plasma TMAO level,the patients were also assigned into low(＜2.44 μmol/L,38 cases),median(2.44 μmol/L≤TMAO＜5.18 μmol/L,37 cases)and high TMAO(≥5.18 μmol/L,37 cases)groups.ROC curve analysis was used to assess the predictive value of plasma TMAO level for high imaging burden in diabetic patients with CSVD.Binary logistic regression analysis was employed to analyze the correlation between plasma TMAO level and high imaging burden.Results The high burden group exhibited significantly higher plasma TMAO level than the low burden group(P=0.002).The AUC value of plasma TMAO level in predicting high imaging burden was 0.669(95％CI:0.569-0.769,P=0.002).The percentage of high imaging burden was 34.2％,54.1％and 64.9％,respectively among the low,median and high TMAO groups,with significant differences among them(Chi-square=7.270,P=0.026).Binary logistic regression analysis indicated the correlation between TMAO and high imaging burden(OR=1.178,95％CI:1.019-1.364,P=0.027).Conclusion In elderly diabetic patients with CSVD,plasma TMAO level is closely associated with high imaging burden,with higher TMAO level,higher risk for high imaging burden.

A total of 269 non-diabetic chronic kidney disease (CKD) patients were enrolled in this study. Among them, 175 patients (65.1%) were assigned to the control group and received conventional therapy with maximally tolerated doses of renin-angiotensin-aldosterone system inhibitors, while 94 patients (34.9%) were assigned to the dapagliflozin group and received oral dapagliflozin 10 mg/day in addition to the conventional therapy. The results showed that the urine protein quantity in the dapagliflozin group was lower than those in the control group at 3, 6, 12, 18, and 24 months of follow-up (all P<0.05), and the blood albumin level was higher than those in the control group at 18 and 24 months of follow-up (all P<0.05). The Kaplan-Meier survival curve analysis results showed that the cumulative renal survival rate of the dapagliflozin group was significantly higher than that of the control group (Log-rank test, χ2=5.078, P=0.024). Multivariable Cox regression analysis results revealed that using dapagliflozin was independently associated with a reduced risk of the composite endpoint in non-diabetic CKD patients ( HR=0.400, 95% CI 0.163-0.983, P=0.046). There was no statistical difference in adverse reactions between the two groups (all P>0.05). It is indicated that dapagliflozin has a renal protective effect independent of hypoglycemic action and good safety.

Diagnosis and treatment of refractory hydrocephalus are the keys in reflecting the overall level of diagnosis and treatment of hydrocephalus. However, there is currently no clear definition of refractory hydrocephalus; moreover, treatment of these patients is difficult, with high failure rate. This article focuses on the definition, common causes and classification of refractory hydrocephalus, the treatment strategies of infectious refractory hydrocephalus, the treatment dilemmas of negative pressure or low-pressure hydrocephalus, and treatment future directions of refractory hydrocephalus, in order to attract attention of clinicians to the diagnosis and treatment of refractory hydrocephalus.

Objective To explore the application of artificial intelligence quantitative analysis in the prognostic assessment of patients with connective tissue disease-associated interstitial lung disease(CTD-ILD).Methods A total of 67 patients with CTD-ILD were retrospectively selected.All subjects underwent high-resolution computed tomography(HRCT)scanning and were categorized into three groups,namely mild,moderate and severe groups,based on the results of pulmonary function tests.The survival rates of patients in each group were compared using Kaplan-Meier curves and analysis of variance.The univariate analysis was employed to assess the rela-tionships between artificial intelligence parameters and patient prognosis.Significant results were then incorporated into a multifacto-rial Cox regression model to construct the most accurate predictive model.Results A significant difference in survival rate was observed among the three groups(P<0.05).Univariate analysis revealed that the volume and percentage of lung infection in deceased patients were significantly greater than those in surviving patients,while the lung volume in deceased patients was significantly smaller than that in surviving patients.The analysis showed left lung volume and the percentage of lesion components CT value≤-750 HU as risk factors for prognosis,and the combination of these two factors as the most effective predictive model.Conclusion The artificial intelligence analysis system for lung lesions provides a new systematic and quantitative method for the prognostic assessment of CTD-ILD patients,which can be used for the prognostic assessment and follow-up of CTD-ILD patients.

Objective:To evaluate the role of tubulin tyrosin ligase like-6 (TTLL6)-mediated microtubule polyglutamylation and Spastin(a microtubule cleaving protein)-induced excessive microtubule cleavage in the developmental impairment of dendritic spines in neonatal mice following repeated sevoflurane anesthesia, by utilizing TTLL6 conditional knockout mice.Methods:Fifty SPF female TTLL6 brain tissue-specific knockout (TTLL6 CKO: Camk2-Cre + ; TTLL6 f/f) and fifty control (TTLL6 CON: TTLL6 f/f) mice with C57BL/6J background, aged 6 days old were selected.TTLL6 CKO mice were divided into TTLL6 CON control group and TTLL6 CON sevoflurane group, and TTLL6 CKO mice were divided into TTLL6 CKO control group and TTLL6 CKO sevoflurane group, with 25 mice in each group by random block method.Mice in the sevoflurane groups were exposed to 3% sevoflurane with 60% O 2 for 2 hours daily on postnatal days 6, 8, and 10.The mice in control groups received only 60% O 2 under the same condition.The polyGlu-Tubulin and postsynaptic density 95(PSD95) protein expression were detected using Western blot. The expressions of TTLL6, Spastin, and α-Tubulin were assessed via immunofluorescence.Golgi staining and electron microscopy were employed to observe the density of hippocampal dendritic spines and synaptic conditions. The Morris water maze test was used to evaluate spatial memory capabilities. Statistical analysis was performed using GraphPad Prism 8.0 software. Results:(1) Behavioral results showed significant time and group interactions among the four groups in terms of latency to find the platform ( F=8.22, P<0.001).Mice in the TTLL6 CON sevoflurane group had a significantly longer escape latency on days 3-7 compared with the TTLL6 CON control group (all P<0.05), while there was no significant difference between the TTLL6 CKO sevoflurane group and the TTLL6 CKO control group (all P>0.05). The number of platform crossings differed significantly among the four groups ( H=11.95, P=0.007).The TTLL6 CON sevoflurane group had significantly fewer crossing times than the TTLL6 CON control group ( P<0.05), but no significant difference was observed between the TTLL6 CKO sevoflurane group and the TTLL6 CKO control group ( P>0.05). (2) Golgi staining and electron microscopy results revealed significant differences in dendritic spine density and synapse number among the four groups( F=29.00, 41.94, both P<0.001). The dendritic spine density ((5.83±0.40)/10 μm) and the number of synapses ((3.67±0.58)/10 μm) in the TTLL6 CON sevoflurane group were both significantly lower than those in the TTLL6 CON control group ((12.87±1.70)/10 μm, (9.33±0.57)/10 μm)(both P<0.05). In contrast, there was no statistically significant difference between the TTLL6 CKO sevoflurane group and TTLL6 CKO control group (both P>0.05). (3) Immunofluorescence results showed significant differences in the percentage of TTLL6 and Spastin and α-Tubulin co-expressed positive cells in the CA3 region of the hippocampus among the four groups of mice ( F=215.20, 26.08, both P<0.001). The percentage of TTLL6 and Spastin and α-Tubulin co-expressed positive cells in the TTLL6 CON sevoflurane group ((16.75±1.81) %, (47.98±8.42) %) were significantly higher than those in the TTLL6 CON control group ((2.44±0.58) %, (20.07±4.54) %)(both P<0.05), while there was no statistically significant difference between the TTLL6 CKO sevoflurane group and TTLL6 CKO control group ( P>0.05). (4) Western blot results indicated significant differences in the expression of polyGlu-Tubulin and PSD95 proteins in the hippocampal tissue among the four groups of mice ( F=19.66, 8.57, both P<0.001). The TTLL6 CON sevoflurane group had higher polyGlu-Tubulin expression (0.86±0.19) and lower PSD95 expression (0.61±0.13) compared to the TTLL6 CON control group (0.51±0.11, 1.01±0.07) (both P<0.05).However, there was no significant difference between the TTLL6 CKO sevoflurane group and the TTLL6 CKO control group ( P>0.05). Conclusion:The mechanism underlying long-term cognitive impairment in developing brain of neonatal mice caused by repeated sevoflurane anesthesia may relate to the upregulation of TTLL6-induced microtubule polyglutamylation and accelerated Spastin-mediated microtubule severing, which ultimately leads to abnormal dendritic spine development.

Objective To investigate the association between gut microbiota metabolite,trimethy-lamine-N-oxide(TMAO),and total imaging burden in diabetic patients with cerebral small vessel disease(CSVD).Methods A prospective study was conducted on 112 elderly diabetic patients with CSVD admitted in our hospital from June 2022 to May 2024.According to the total imaging burden score,they were divided into a high burden group(burden score≥2,57 cases)and a low burden group(burden score＜2,55 cases).High-performance liquid chromatography with online electrospray ionization tandem mass spectrometry was applied to detect the plasma level of TMAO.Then based on the tertile of plasma TMAO level,the patients were also assigned into low(＜2.44 μmol/L,38 cases),median(2.44 μmol/L≤TMAO＜5.18 μmol/L,37 cases)and high TMAO(≥5.18 μmol/L,37 cases)groups.ROC curve analysis was used to assess the predictive value of plasma TMAO level for high imaging burden in diabetic patients with CSVD.Binary logistic regression analysis was employed to analyze the correlation between plasma TMAO level and high imaging burden.Results The high burden group exhibited significantly higher plasma TMAO level than the low burden group(P=0.002).The AUC value of plasma TMAO level in predicting high imaging burden was 0.669(95％CI:0.569-0.769,P=0.002).The percentage of high imaging burden was 34.2％,54.1％and 64.9％,respectively among the low,median and high TMAO groups,with significant differences among them(Chi-square=7.270,P=0.026).Binary logistic regression analysis indicated the correlation between TMAO and high imaging burden(OR=1.178,95％CI:1.019-1.364,P=0.027).Conclusion In elderly diabetic patients with CSVD,plasma TMAO level is closely associated with high imaging burden,with higher TMAO level,higher risk for high imaging burden.

A total of 269 non-diabetic chronic kidney disease (CKD) patients were enrolled in this study. Among them, 175 patients (65.1%) were assigned to the control group and received conventional therapy with maximally tolerated doses of renin-angiotensin-aldosterone system inhibitors, while 94 patients (34.9%) were assigned to the dapagliflozin group and received oral dapagliflozin 10 mg/day in addition to the conventional therapy. The results showed that the urine protein quantity in the dapagliflozin group was lower than those in the control group at 3, 6, 12, 18, and 24 months of follow-up (all P<0.05), and the blood albumin level was higher than those in the control group at 18 and 24 months of follow-up (all P<0.05). The Kaplan-Meier survival curve analysis results showed that the cumulative renal survival rate of the dapagliflozin group was significantly higher than that of the control group (Log-rank test, χ2=5.078, P=0.024). Multivariable Cox regression analysis results revealed that using dapagliflozin was independently associated with a reduced risk of the composite endpoint in non-diabetic CKD patients ( HR=0.400, 95% CI 0.163-0.983, P=0.046). There was no statistical difference in adverse reactions between the two groups (all P>0.05). It is indicated that dapagliflozin has a renal protective effect independent of hypoglycemic action and good safety.