BACKGROUND: Postoperative pulmonary complications (PPCs) are major adverse events in neurosurgical patients. This study aimed to develop and validate machine learning models predicting PPCs after neurosurgery. METHODS: PPCs were defined according to the European Perioperative Clinical Outcome standards as occurring within 7 postoperative days. Data of cases meeting inclusion/exclusion criteria were extracted from the anesthesia information management system to create three datasets: The development (data of Huashan Hospital, Fudan University from 2018 to 2020), temporal validation (data of Huashan Hospital, Fudan University in 2021) and external validation (data of other three hospitals in 2023) datasets. Machine learning models of six algorithms were trained using either 35 retrievable and plausible features or the 11 features selected by Lasso regression. Temporal validation was conducted for all models and the 11-feature models were also externally validated. Independent risk factors were identified and feature importance in top models was analyzed. RESULTS: PPCs occurred in 712 of 7533 (9.5%), 258 of 2824 (9.1%), and 207 of 2300 (9.0%) patients in the development, temporal validation and external validation datasets, respectively. During cross-validation training, all models except Bayes demonstrated good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.840. In temporal validation of full-feature models, deep neural network (DNN) performed the best with an AUC of 0.835 (95% confidence interval [CI]: 0.805-0.858) and a Brier score of 0.069, followed by Logistic regression (LR), random forest and XGBoost. The 11-feature models performed comparable to full-feature models with very close but statistically significantly lower AUCs, with the top models of DNN and LR in temporal and external validations. An 11-feature nomogram was drawn based on the LR algorithm and it outperformed the minimally modified Assess respiratory RIsk in Surgical patients in CATalonia (ARISCAT) and Laparoscopic Surgery Video Educational Guidelines (LAS VEGAS) scores with a higher AUC (LR: 0.824, ARISCAT: 0.672, LAS: 0.663). Independent risk factors based on multivariate LR mostly overlapped with Lasso-selected features, but lacked consistency with the important features using the Shapley additive explanation (SHAP) method of the LR model. CONCLUSIONS: The developed models, especially the DNN model and the nomogram, had good discrimination and calibration, and could be used for predicting PPCs in neurosurgical patients. The establishment of machine learning models and the ascertainment of risk factors might assist clinical decision support for improving surgical outcomes. TRIAL REGISTRATION ChiCTR 2100047474; https://www.chictr.org.cn/showproj.html?proj=128279 .
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Algorithms ; Lung Diseases/etiology* ; Machine Learning ; Neurosurgical Procedures/adverse effects* ; Postoperative Complications/diagnosis* ; Risk Factors ; ROC Curve

Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

Objective:To understand the molecular transmission characteristics of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome(AIDS) patients in the mountainous area of southwest Zhejiang Province(Lishui city).Methods:A total of 147 blood samples were collected from newly-diagnosed HIV-1 infected who received no antiviral therapy, and pol gene was amplified, followed by sequencing. MEGA6.0 software was used to construct phylogenetic tree and determine gene subtypes. HIVDB online was used to analyze drug resistance mutation, then the pairwise genetic distance(GD) was calculated and the opitimal threshold of GD was selected, finally the molecular transmission network was constructed by Cytoscape3.7.0 software. Chi-square or Fisher′s exact probability method was used for statistical analysis. Results:A total of 134 sequences were obtained successfully, and nine subtypes were detected. The dominant subtypes were CRF08_BC (34.33%, 46/134), CRF01_AE (29.85%, 40/134) and CRF07_BC (23.88%, 32/134). It also found that age, registered residence, education level and transmission route had significant differences in distribution of subtypes ( P<0.05). Nineteen drug resistance individuals were found, and the total drug resistance rate was 14.18% (19/134). The HIV-1 molecular transmission network was plotted based on 1.2% GD threshold. A total of 15 transmission clusters (cluster size ranging from 2 to 29) were found. The network access rate was 49.25% (66/134), mainly including male (75.76%, 50/66), heterosexual (81.82%, 54/66) and patientsrinfected with CRF08_ BC (50.00%, 33/66). A transmission cluster including two cases of female sex workers and seven cases of drug resistance was identified, in which the average age of the patients was 57.21 years old and the average degree value was 22.7, and the cases were mainly infected through heterosexual contact (96.55%, 28/29). The highest homology of the sequences in the cluster was in Yunnan. Conclusions:The HIV-1 subtypes were diverse in the mountainous area of southwest Zhejiang Province(Lishui city). Drug resistant transmission had reached a moderate epidemic level. There were molecular transmission clusters with the aggregation characteristics of elderly clients in specific regions. It was urgent to formulate and implement precise intervention strategies to curb the spread of HIV.

Objective:To compare the performance of four commercial kits for anti-HIV confirmatory assay and to provide a reference for clinical application.Methods:Two western blot (WB) kits and two recombinant immunoblot assay/line immune assay kits were used to detect 185 samples in parallel, McNermar test was used to analyze the consistency between the testing results and HIV infection status. Compared to the testing result of the most used MP company’s WB kit, the odds ratio ( OR) was calculated. Results:The consistency of the testing results with the status of HIV infection by the four kits was 83.24%-92.43%, and the Kappa value was 0.558-0.831.The OR value of IMT company’s WB kit obtained from 57 HIV-uninfected samples was 0.932(95% CI: 0.446-1.946, P=0.851), and the OR values of WT company’s recombinant immunoblot assay (RIBA) and MK company’s line immune assay (LIA) were 2.348(95% CI: 1.069-5.158, P=0.034) and 23.064 (95% CI: 5.125-103.789, P<0.001), respectively. The OR value of LIA obtained from 128 HIV-infected samples was 0.153 (95% CI: 0.034-0.700, P=0.016). LIA showed fewest reactions by testing 95 HIV positive screening samples, which was significantly different from any other kit ( P< 0.05). There was no significant difference among the other three kits. In the case of non-specific reactions, the numbers of bands were all ≤4, and the proportion of light-colored bands accounted for 52.1% (37/71). The main bands were gp160(81.3%), p24(71.9%), and p17(28.1%). Conclusions:There was no significant difference between the two WB kits. The RIBA/LIA detection kits could reduce the generation of indeterminate result, but the LIA kit has the risk of false negative for weakly reactive samples.

Objective:To investigate the relationship between HIV-infected men who have sex with men and their sexual partners in Zhejiang province.Methods:A cross-sectional survey was conducted to recruit newly confirmed HIV/AIDS among MSM from 2015 to 2017, including sexual partner identification and molecular epidemiological study. Plasma was collected to extract RNA, and the pol gene of HIV-1 was amplified by RT-PCR/nested PCR. Phylogenetic tree and molecular transmission cluster were analyzed to identify the transmission relationship between sexual partners. Results:A total of 937 HIV/AIDS among MSM were recruited to promote HIV testing for their sexual partners, and 173 positive sexual partners were identified. 50.8% (61/120) of the gene sequences were clustered among the positive sex partners. Seven pairs of clustered sex partners combined with the results of recent infection preliminarily determined the transmission direction. In the clusters, there were statistical differences between the partners who were diagnosed in the same year ( OR=12.190, 95% CI: 1.563-95.054) or with current residence in the different districts ( OR=17.054, 95% CI: 1.742-166.982). Conclusions:Combined with a molecular transmission network, HIV test for the sexual partners of HIV/AIDS among MSM can improve the accurate tracking of cases and preliminarily determine the direction of transmission, according to the results of recent infection. It is suggested that after HIV is confirmed for HIV/AIDS among MSM, HIV tests should be carried out as soon as possible for their sexual partners, including a cross-regional sexual partner tracking test, which is helpful to improve the tracing procedure.

OBJECTIVE: To explore the serological feature and molecular mechanism for a case with A307 subgroup of the ABO blood group system. METHODS: Serological assay was carried out to determine the ABO blood group of the proband and his family members. Genotypes for exons 1 to 7 of the ABO gene were determined with sequence-specific primer polymerase chain reaction (SSP-PCR) and direct sequencing. The impact of the variant on the stability of alpha-1,3-N-acetylgalactosaminyltransferase (GTA) was predicted through construction of a 3D molecular model. RESULTS: The proband, his brother and daughter were diagnosed with Aend phenotype by serological analysis. Their ABO genotype was determined as A307/O02, with heterozygous c.467C>T (p.P156L) and c.745C>T (p.R249W) variants identified in exon 7 of the ABO gene. Molecular modeling suggested that the p.R249W variant may alter the number of hydrogen bonds between the amino acids. The protein was predicted to have a decreased Δ Δ G value of thermodynamic stability. CONCLUSION The p.R249W variant may give rise to the A307 subgroup by reducing the stability of the GTA enzyme, leading to serological features of Aend phenotype.

Objective:To evaluate the applicability of limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA, LAg for short) in determining the new HIV-1 infection status of MSM population with seroconversion and make correlation analysis of other biological indicators.Methods:The 15 cases with HIV seroconversion were found in a MSM observation cohort for calculating the HIV prevalence in Zhejiang.The subjects were conducted epidemiological investigation and sampled.The interval of infection time was estimated according to the exposure history and the time of HIV-positive confirmation.LAg, immunoblotting, CD4 cell counting and viral load test were applied in the testing of the related blood samples. McNermar test was conducted for consistency of the two methods.Results:Of 15 cases, the average age was (31.5±8.0) years old, ranging from 24 to 57 years old. The interval of infection time ranged from 40 days to 366 days, and the median was 134 days, with inter-quartile range from 89 to 180 days. A total of 7 cases were classified as new HIV-1 infection by LAg, and 8 cases were classified as chronic infection.The consistent rate was high to 86.67%, and kappa value was 0.73.The samples lacking at least two bands in p31, p51, p66 and gp120 by immunoblotting were determined as recent infection, of which the new infection proportion was significantly higher than that of other samples ( P=0.029).There was no statistical difference in the distribution of CD4 counts ( P=0.533) and viral loads ( P=0.467) between the new infection and chronic infection groups that divided by LAg. Conclusion:By combining with exposure history, the limiting antigen avidity enzyme immunoassay can be used to estimate the new HIV-1 infection.The other biological indicators such as immunoblotting bands, CD4 cell counts and viral loads, can be used as accessory indicators in evaluating the status of new HIV-1 infection.

Objective:To evaluate the applicability of limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA, LAg for short) in determining the new HIV-1 infection status of MSM population with seroconversion and make correlation analysis of other biological indicators.Methods:The 15 cases with HIV seroconversion were found in a MSM observation cohort for calculating the HIV prevalence in Zhejiang.The subjects were conducted epidemiological investigation and sampled.The interval of infection time was estimated according to the exposure history and the time of HIV-positive confirmation.LAg, immunoblotting, CD4 cell counting and viral load test were applied in the testing of the related blood samples. McNermar test was conducted for consistency of the two methods.Results:Of 15 cases, the average age was (31.5±8.0) years old, ranging from 24 to 57 years old. The interval of infection time ranged from 40 days to 366 days, and the median was 134 days, with inter-quartile range from 89 to 180 days. A total of 7 cases were classified as new HIV-1 infection by LAg, and 8 cases were classified as chronic infection.The consistent rate was high to 86.67%, and kappa value was 0.73.The samples lacking at least two bands in p31, p51, p66 and gp120 by immunoblotting were determined as recent infection, of which the new infection proportion was significantly higher than that of other samples ( P=0.029).There was no statistical difference in the distribution of CD4 counts ( P=0.533) and viral loads ( P=0.467) between the new infection and chronic infection groups that divided by LAg. Conclusion:By combining with exposure history, the limiting antigen avidity enzyme immunoassay can be used to estimate the new HIV-1 infection.The other biological indicators such as immunoblotting bands, CD4 cell counts and viral loads, can be used as accessory indicators in evaluating the status of new HIV-1 infection.

Objective To evaluate the role of heparanase in endotoxemia-induced destruction of vascular endothelial glycocalyx in rats.Methods Forty-eight pathogen-free male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-250 g, were randomly divided into 3 groups (n=16 each) using a random number table: control group (group C), lipopolysaccharide (LPS) group (group L) and LPS+ heparin group (group LH).Endotoxemia was induced by intravenous LPS 15 mg/kg in L and LH groups, and heparin sodium 100 U · kg-1 · h-1 was infused simultaneously in group LH.At 3 and 6 h after LPS injection, blood samples were collected from the femoral vein for determination of the serum concentrations of serum heparin sulfate (HS), syndecan-1, E-selectin and intercellular adhesion molecule-1 (ICAM-1) concentrations.The rats were then sacrificed, and lungs were removed for microscopic examination and for determination of wet/dry lung weight ratio (W/D ratio).Results Compared with group C, the serum HS, syndecan-1, E-selectin and ICAM-1 concentrations and W/D ratio were significantly increased in group L, and the serum HS and ICAM-1 concentrations were increased in group LH (P＜0.05).Compared with group L, the serum HS, syndecan-1, E-selectin and ICAM-1 concentrations and W/D ratio were significantly decreased in group LH (P＜0.05).The pathological changes of lungs were obvious in group L, and were significantly mitigated in group LH.Conclusion Heparanase is involved in endotoxemiainduced destruction of vascular endothelial glycocalyx in rats.