[Exploration of the effect of blood lipids on the lesion distribution pattern in acute ischemic stroke based on MRI study with population standard spatial analysis].

Objective: To explore the effect of blood lipids on the lesion distribution pattern in patients with acute ischemic stroke by using MRI technology based on population standard spatial analysis. Methods: The MRI data of 1 202 patients with acute ischemic stroke in General Hospital of Eastern Theater Command from January 2015 to December 2020 and Nanjing First Hospital from January 2013 to December 2021 were retrospectively collected, including 871 males and 331 females, aged 26 to 94 (64±11) years. According to the condition of blood lipids, they were divided into the dyslipidemia group (n=683) and the normal blood lipids group (n=519). After the automatic segmentation of diffusion-weighted imaging (DWI) images by artificial intelligence, the infarct sites were registered to the standard space which was used to draw the frequency heat map. The chi-square test was used to compare the difference in lesion location between the two groups. Generalized linear model regression analysis was used to observe the correlation between each blood lipid index and lesion site, and inter-group comparison and correlation analysis were used to observe the relationship between each blood lipid index and lesion volume. Results: Compared with the normal blood lipid group, the lesions in the dyslipidemia group were more extensive, mostly distributed in the occipital temporal region of the right posterior cerebral artery and the frontal region of the left middle cerebral artery. The brain regions of higher triglyceride(TG) and higher low-density lipoprotein cholesterol(LDL-C) groups were concentrated in the posterior circulation. The brain regions in the higher total cholesterol(TC) and lower high-density lipoprotein cholesterol(HDL-C) groups were concentrated in the anterior circulation(all P<0.05). In the anterior circulation infarct volume, the higher TC group was significantly higher than the normal TC group[(27.58±5.34) vs (17.73±1.18)ml, P=0.029]. In the posterior circulation infarct volume, the higher LDL-C group and the TG group were significantly higher than the normal LDL-C and TG groups[(7.55±2.51) vs (3.55±0.31) ml; (5.76±1.19) vs (3.36±0.30) ml](both P<0.05). Correlation analysis showed that TC and LDL-C were non-linearly (U-shaped) correlated with anterior circulation infarct volume (both P<0.05). Conclusions: Different blood lipids have effects on the distribution pattern and volume of ischemic stroke infarcts. Different hyperlipidemia is related to the specific distribution site and the larger extent of infarction.

[Metagenomic data-analysis reveals enrichment of lipopolysaccharide synthesis in the gut microbiota of atrial fibrillation patients].

Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.

[Resting-state functional magnetic resonance imaging analysis of abnormal directional functional connectivity of the nucleus accumbens in patients with chronic tinnitus].

Objective: To investigate abnormal directional functional connectivity of the nucleus accumbens (NAc) in chronic tinnitus patients using resting-state functional magnetic resonance imaging (fMRI), and to determine the relationship between the degree of this connectivity and tinnitus characteristics. Methods: The resting-state fMRI data of 40 patients with bilateral chronic tinnitus (12 males and 28 females, aged from 26 to 63(50.6±11.6) years) and 40 healthy controls with normal hearing (16 males and 24 females, aged from 26 to 70(45.9±12.4)years) were retrospectively enrolled from the Department of Otolaryngology, Nanjing First Hospital from January 2017 to January 2020. The bilateral NAc were selected as seeds to detect the directional functional connectivity with the whole brain, then the effective connectivity values between the two groups were compared using Granger Causality Analysis (GCA), and the correlation between the effective connectivity and the characteristics of tinnitus was calculated. Results: Compared with healthy controls, the effective connectivity from the left NAc to left middle frontal gyrus in patients with bilateral chronic tinnitus was increased [(1.0±0.2)vs(0.6±0.3)], the effective connectivity from the right NAc to left inferior frontal gyrus was enhanced [(0.9±0.3)vs(0.6±0.4)], the effective connectivity from the right middle temporal gyrus to left NAc was enhanced [(1.0±0.2)vs(0.5±0.3)], the effective connectivity from the right middle frontal gyrus to right NAc was also enhanced[(1.0±0.2)vs(0.5±0.3)](all P<0.05). After adjusting for age, gender, education level, and gray matter volume, positive correlations was observed between the Tinnitus Handicap Questionnaire (THQ) scores and increased effective connectivity values from the left NAc to the left middle frontal gyrus (r=0.386, P=0.020). Additionally, enhanced effective connectivity values from the right middle frontal gyrus to the right NAc was also positively associated with tinnitus duration (r=0.390, P=0.019). Conclusion: The directional functional connectivity between the NAc and prefrontal cortex in patients with chronic tinnitus is enhanced.

[Effects of iASSIST navigation system and personal specific instrument assisted total knee arthroplasty in the treatment of osteoarthritis].

Objective: To compare the application of iASSIST assisted total knee arthroplasty (TKA) and three-dimentional(3D) printing personal specific instrument (PSI) assist TKA in the treatment of osteoarthritis (OA). Methods: Clinical data of 47 patients with OA admitted at Department of Orthopaedic Surgery in Nanjing Medical University Nanjing Hospital between April and September 2016 were retrospectively reviewed, including 20 males and 27 females, aging from 57 to 77 years with mean age of (63.8±8.2) years. They were randomly divided into iASSIST-TKA group (23 patients) and PSI-TKA group (24 patients). The data such as hip knee ankle (HKA) angle, frontal femoral component (FFC) angle, frontal tibial component (FTC) angle, lateral femoral component (LFC) angle, lateral tibial component (LTC) angle, time of operation, post-operative wound drainage, period of hospitalization, visual analog scale (VAS) and Knee Society Score (KSS) at 1 day, 7 days, 14 days, 1 month and 3 months were recorded and compared between the two groups. T test was used to compare measurement data, Fisher exact test and χ(2) test were applied to enumeration data in comparison among groups, and Kruskal-Wallis test was applied to ranked data. Results: The deviation values of HKA, FFC, LFC, FTC and LTC angles were all below 3°(-2° to 2°), and there were no significant difference between iASSIST-TKA group and PSI-TKA group (Z=-0.610 to 0.000, P=0.542 to 1.000). Compared to PSI-TKA group, the time of operation was long((80.7±8.8) minutes vs.(60.2±7.8) minutes), the amount of post-operative wound drainage was increased((210.7±32.1) ml vs.(185.5±30.2)ml) and the period of hospitalization decreased((5.4±2.4) d vs.(6.7±1.6) d) in iASSIST-TKA group, there were significant difference(t=-2.190 to 8.460, P=0.000 to 0.033). There were no significant difference in intra-operative blood drainage((18.4±5.4) ml vs.(17.3±6.2) ml) between the two groups(t=0.650, P=0.521). PSI-TKA group had a superior VAS score(4.8±0.6 vs. 5.5±0.9, 3.6±0.8 vs. 4.3±0.9), KSS clinical score(49.3±5.5 vs. 44.2±6.4, 54.9±4.0 vs. 50.8±4.2) and KSS function score(44.1±2.9 vs. 41.2±3.5, 49.6±3.8 vs. 46.6±3.2) in 1 day and 7 days post-operation(t=-3.420 to 3.150, P=0.001 to 0.007). There were no significant difference in VAS and KSS score in 14 days, 1 month and 3 months post-operation(t=-1.390 to 0.530, P=0.170 to 1.000) between the two groups. Conclusions: The iASSIST-TKA and PSI-TKA can help to make TKA procedure more accurately. iASSIST-TKA may take longer time of operation and have slower recovery, PSI-TKA may need more X-ray input and longer period of hospitalization. The long-term research of both techniques may be valuable for the further clinical usage.

A novel mutation links to von Hippel-Lindau syndrome in a Chinese family with hemangioblastoma.

Hemangioblastoma of the central nervous system occurs as sporadic tumors or as a part of von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary tumor syndrome caused by a germline mutation in the VHL tumor suppressor gene. We screened a Chinese family with VHL for mutations in the VHL gene and evaluated a genetic test for diagnosing VHL disease and clinical screening of family members. DNA extracted from the peripheral blood of all live members and from tissue of deceased family members with VHL disease was amplified by polymerase chain reaction to 3 VHL gene exons. Mutations in the amplification products were compared against the Human Gene Mutation Database. The involvement of multiple organs among the kindred with VHL disease was confirmed by medical history and radiography. Of the 12 members of the 4-generation family, 5 were diagnosed with VHL disease. Patient age at the initial diagnosis was 26-36 years (mean = 31 years). The mean time was 15 (11-19 months) from symptom appearance to the first patient visit to the hospital. Sequence analysis revealed that the frameshift mutation 327del C (p.Gly39Alafs*26) in exon 1 affected all family members, but not the healthy individuals or 16 unrelated controls. Members without gene mutation showed no clinical manifestation of VHL disease. We detected a conserved novel frameshift mutation in the VHL gene of the family members that contributes to VHL. DNA analysis of VHL is advantageous for VHL diagnosis. We developed a quick and reliable method for VHL diagnosis.

Clinical significance of carcinoembryonic antigen-, cytokeratin 19-, or survivin-positive circulating tumor cells in the peripheral blood of esophageal squamous cell carcinoma patients treated with radiotherapy.

Circulating tumor cells (CTCs) have been associated with clinical outcome in various malignancies. The aim of this study was to examine CTC status in the peripheral blood of patients with esophageal squamous cell carcinoma (ESCC) before and after radiotherapy, and to evaluate its clinical significance. A total of 72 ESCC patients treated with radical radiotherapy were enrolled in this study. The nested reverse-transcriptase polymerase chain reaction was used to detect the three representative markers of CTCs, namely carcinoembryonic antigen, cytokeratin 19, and survivin. The results showed that CTC(+), a status with positive expression of at least one of these three markers, in patients with ESCC pre- and post-radiotherapy were 54.2% (39/72) and 38.9% (28/72), respectively (P= 0.059). Furthermore, CTC (+) in patients pre- or post-radiotherapy was both correlated with lymph metastasis and adverse 2-year progression-free survival. It was also found that changes in CTC status after radiotherapy could reflect patients' response to radiotherapy. The response rates in cases with CTC status pre-radiotherapy(+)/post-radiotherapy(+), pre-radiotherapy(-)/post-radiotherapy(+), pre-radiotherapy(-)/post-radiotherapy(-), pre-radiotherapy(+)/post-radiotherapy(-) were 58.3% (21/36), 0% (0/3), 73.7% (14/19), and 85.7% (12/14), respectively. In a multivariate analysis of Cox proportional hazard model, only CTC (+) post-radiotherapy was an independent unfavorable prognostic factor for ESCC apart from subsequent chemotherapy and patients' Karnofsky performance status scores. In conclusion, positive detection of CTCs in patients with ESCC after radiotherapy may be a promising biomarker for radiation efficiency and prognosis assessment in ESCC.