[The efficacy and safety of protein A immunoadsorption combined with rituximab treatment for highly sensitized patients undergoing haplo-hematopoietic stem cell transplantation].

Objective: To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured. Results: After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) (P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) (P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0-15 989) (P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 (P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions: The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.

Prediction of programmed death-1 expression status in non-small cell lung cancer based on intratumoural and peritumoral computed tomography (CT) radiomics nomogram.

AIMS: This study aimed to predict the expression of programmed death-1 (PD-1) in non-small cell lung cancer (NSCLC) using intratumoral and peritumoral computed tomography (CT) radiomics nomogram. MATERIALS AND METHODS: Two hundred patients pathologically diagnosed with NSCLC from two hospitals were retrospectively analyzed. Of these, 159 NSCLC patients from our hospital were randomly divided into a training cohort (n=96) and an internal validation cohort (n=63) at a ratio of 6:4, while 41 NSCLC patients from another medical institution served as the external validation cohort. The radiomic features of the gross tumor volume (GTV) and peritumoral volume (PTV) were extracted from the CT images. Optimal radiomics features were selected using least absolute shrinkage and selection operator regression analysis. Finally, a CT radiomics nomogram of clinically independent predictors combined with the best rad-score was constructed. RESULTS: Compared with the 'GTV' and 'PTV' radiomics models, the combined 'GTV + PTV' radiomics model showed better predictive performance, and its area under the curve (AUC) values in the training, internal validation, and external validation cohorts were 0.90 (95% confidence interval [CI]: 0.83-0.97), 0.85 (95% CI: 0.74-0.96) and 0.78 (95% CI: 0.63-0.92). The nomogram constructed by the rad-score of the 'GTV + PTV' radiomics model combined with clinical independent predictors (prealbumin and monocyte) had the best performance, with AUC values in each cohort being 0.92 (95% CI: 0.85-0.98), 0.88 (95% CI: 0.78-0.97), and 0.80 (95% CI: 0.66-0.94), respectively. CONCLUSION: The intratumoral and peritumoral CT radiomics nomogram may facilitate individualized prediction of PD-1 expression status in patients with NSCLC.

Author Correction: Association between hormone replacement therapy and sex hormones in postmenopausal women: a systematic review and meta-analysis.

Correction to: Eur Rev Med Pharmacol Sci 2023; 27 (11): 5264-5279. DOI: 10.26355/eurrev_202306_32646-PMID: 37318501-published online on June 13, 2023. After publication, the authors applied a correction in the Funding section. The section has been amended as follows: This study was supported by a grant from the National Natural Science Foundation of China (No. 81671421). Moreover, the corresponding author's name was wrong. Therefore, in accordance with the email address, the correct corresponding author has been corrected from D.-H. LU to L.-Z. XU. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/32646.

Association between hormone replacement therapy and sex hormones in postmenopausal women: a systematic review and meta-analysis.

OBJECTIVE: The aim of the study was to systematically review and meta-analyze the available data on changes in the hormonal profile of postmenopausal women treated with hormone replacement therapy (HRT). MATERIALS AND METHODS: Full-text articles published up to April 30, 2021, were searched through PUBMED, EMBASE, the Cochrane library and Web of Science (WOS) databases and were screened strictly according to inclusion criteria. Randomized clinical trials and case control studies were enrolled. Studies not reporting steroid serum levels or not providing a control group were excluded from the analysis. Studies enrolling women with genetic defects or severe chronic systemic diseases were excluded. Data are expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Random effect models were used for the meta-analysis. RESULTS: HRT administration increases estradiol (E2) and reduces follicle stimulating hormone (FSH) serum levels compared with pre-treatment. Their changes are evident when oral and transdermal HRT are administered, while vaginal HRT not. No significant effect on E2 and FSH was found between 6 and 12 months, as well as between 12 and 24 months. No significant effect on E2 and FSH was shown between different regimes. No difference was observed between different HRT regarding their effect on lipid profiles, breast pain and vaginal bleeding, but oral estrogen combined synthetic progestin caused a reduction in sex hormone-binding globulin (SHGB). CONCLUSIONS: The review suggested oral and transdermal HRT could lead to a rise in E2 serum levels and a decrease in FSH. The types and doses of HRT did not seem to modify the E2 and FSH level. Also, oral estrogen combined synthetic progestin could cause a reduction in SHGB. This might be crucial when choosing the best possible treatment for each patient individually taking into consideration if potential benefits outweigh the risks.

[Research on the cone-beam CT of the fracture morphology and location of a single oblique complicated crown-root fracture of maxillary incisors].

Objective: To study the morphological pattern of single oblique complex crown fracture and its relative location to periodontal hard tissues from a three-dimensional perspective by using cone-beam CT, which provides a more intuitive and comprehensive understanding for the pathological features and rules of single oblique complex crown fracture. Methods: Primary cone-beam CT images of 56 maxillary permanent anterior teeth with oblique complex crown root fractures were collected from the Department of Integrated Emergency Dental Care, Capital Medical University School of Stomatology during January 2015 to January 2019. Fracture pattern, fracture angle, fracture depth, fracture width, and the relative location of the fracture line to the crest of the adjacent alveolar ridge were retrospectively analyzed. Independent samples t-test was used to compare the differences in angle, depth and width of fractures between sexes and tooth locations, as well as the pre-and post-fracture crown-to-root ratios between different tooth locations. Then the affected teeth were divided into juvenile group (≤18 years), young group (19-34 years) and middle-aged and elderly group (≥35 years). One-way ANOVA was applied to compare the differences in angle, depth and width of fracture between age groups, and Fisher exact test to compare the differences in fracture pattern of the teeth and the relative position of the fracture line to the crest of the adjacent alveolar ridge. Results: There were 35 males and 21 females in 56 patients, aged (28.2±13.2) years. Among the 56 affected teeth, forty-six were maxillary central incisors and 10 were lateral incisors. According to the patients' age and growing stage, they could be divided into the juvenile group (19 cases), the young group (14 cases), and the middle-aged and elderly group (23 cases). Forty-six (82%) affected teeth had an S-shaped fracture pattern, and ten (18%) had a diagonal pattern, in which the fracture angle of the S-shaped fracture line (47.85°±10.02°) was significantly greater than that of the diagonal line (28.30°±8.07°) (P<0.001). The fracture nadir was flush with or below the top of the alveolar crest in 98% (55/56) of cases. The fracture depth was significantly greater in the juvenile group [(1.75±0.73) mm] than in the young group [(1.21±0.68) mm](P=0.042) and in the middle-aged and elderly group [(1.12±0.90) mm] (P=0.001). The width of fractures among 56 patients was (4.75±1.44) mm, which had no statistically significant differences between different age, sex and tooth location groups (P>0.05). There were no statistically significant differences in the crown-to-root ratios after fracture of maxillary central incisors (1.18±0.13) compared to maxillary lateral incisors (1.14±0.20) (t=1.90, P=0.373). Conclusions: The fracture patterns of single oblique complex crown fracture were mainly S-shaped and oblique alignment; the fracture nadir was mostly located within 2.0 mm below the palatal alveolar crest.

[A preliminary study on the tear matrix metalloproteinase 9 point-of-care assay using a domestic kit].

Objective: To compare the point-of-care assays for tear matrix metalloproteinase 9 (MMP-9) using domestic and InflammaDry kits, and to evaluate the feasibility of diagnosing dry eye with the domestic kit. Methods: It was a cross-sectional study. Thirty dry eye patients and 30 age-and sex-matched normal volunteers were continuously enrolled in this cross-sectional study from June 2022 to July 2022. Both domestic and InflammaDry kits were used to detect the tear MMP-9 levels. The positive rates were recorded for qualitative analysis, and the gray ratios of bands (the gray value of detection bands to that of control bands) were collected for quantitative analysis. The correlations of MMP-9 levels with age, ocular surface disease index, fluorescence tear break-up time, tear meniscus height, Schirmer's Ⅰ test score, corneal fluorescein staining score, and meibomian gland dropout were analyzed. The Mann-Whitney U test, paired Chi-square test, Kappa test, and Spearman's correlation coefficient were used for statistical analysis. Results: There were 14 males and 16 females (30 eyes) in the control group, and their age was (39.37±19.55) years. In the dry eye group, 11 males and 19 females (30 eyes), aged (46.87±17.85) years, had moderate to severe dry eye. The positive rates of MMP-9 in tear fluid were significantly different between dry eye patients (InflammaDry: 86.67%; domestic kit: 70.00%) and controls (InflammaDry: 16.67%, P<0.001; domestic kit: 6.67%, P<0.001). Although the sensitivity of the domestic kit was lower than that of the InflammaDry kit (70.0% vs. 86.7%, P=0.001), the specificity was higher (93.3% vs. 83.3%, P=0.001). In dry eye patients, the positive coincidence rate was 80.7% (21/26), the negative coincidence rate was 100% (4/4), and the total coincidence rate was 83.3% (25/30), with no significant difference between the two kits (McNemar test: χ2=3.20, P>0.05), and the results of both kits were consistent (Kappa=0.53, P=0.001). The Spearman's correlation coefficient showed the gray ratios using both kits were positively correlated with the corneal fluorescein staining score (InflammaDry: ρ=0.48, P<0.05; domestic kit: ρ=0.52, P=0.003). Conclusion: The performances of the domestic and InflammaDry kits are consistent in the point-of-care assay for tear MMP-9, and the domestic kit has lower sensitivity but higher specificity.

Unambiguous Experimental Verification of Linear-in-Temperature Spinon Thermal Conductivity in an Antiferromagnetic Heisenberg Chain.

The everlasting interest in spin chains is mostly rooted in the fact that they generally allow for comparisons between theory and experiment with remarkable accuracy, especially for exactly solvable models. A notable example is the spin-1/2 antiferromagnetic Heisenberg chain (AFHC), which can be well described by the Tomonaga-Luttinger liquid theory and exhibits fractionalized spinon excitations with distinct thermodynamic and spectroscopic experimental signatures consistent with theoretical predictions. A missing piece, however, is the lack of a comprehensive understanding of the spinon heat transport in AFHC systems, due to difficulties in its experimental evaluation against the backdrop of other heat carriers and complex scattering processes. Here we address this situation by performing ultralow-temperature thermal conductivity measurements on a nearly ideal spin-1/2 AFHC system copper benzoate Cu(C_{6}H_{5}COO)_{2}·3H_{2}O, whose field-dependent spin excitation gap enables a reliable extraction of the spinon thermal conductivity κ_{s} at zero field. κ_{s} was found to exhibit a linear temperature dependence κ_{s}∼T at low temperatures, with κ_{s}/T as large as 1.70 mW cm^{-1} K^{-2}, followed by a precipitate decline below ∼0.3 K. The observed κ_{s}∼T clarifies the discrepancies between various spin chain systems and serves as a benchmark for one-dimensional spinon heat transport in the low-temperature limit. The abrupt loss of κ_{s} with no corresponding anomaly in the specific heat is discussed in the context of many-body localization.

Duodenal Permeability Is Associated With Mucosal Microbiota in Compensated Cirrhosis.

INTRODUCTION: Several complications of decompensated cirrhosis are believed to result from increased intestinal permeability. However, little is known about the relationship between mucosal bacteria and epithelial permeability in cirrhosis. We aimed to assess epithelial permeability and associations with mucosal bacteria in patients with compensated cirrhosis. METHODS: We obtained duodenal tissue biopsies from patients with compensated cirrhosis and controls. Patients were excluded if they used antibiotics or immunosuppression. The composition of mucosal microbiota was determined by 16S rRNA gene sequencing and epithelial permeability by transepithelial electrical resistance (TEER) and tight junction protein expression. RESULTS: We studied 24 patients with compensated cirrhosis and 20 controls. Patients with cirrhosis were older than controls (62 vs 52 years, P = 0.02) but had a similar number of extrahepatic comorbidities (2.2 vs 1.4, P = 0.13). Patients with compensated cirrhosis had lower duodenal TEER (i.e., increased epithelial permeability; 13.3 Ω/cm 2 ± 3.4 vs 18.9 Ω/cm 2 ± 7.1; P = 0.004). Patients with compensated cirrhosis trended toward a distinct mucosal microbiota community structure relative to controls ( P = 0.09). Clustering analysis identified two unique enterotypes. These enterotypes differed in bacterial composition and also TEER. A beta-binomial model found 13 individual bacteria associated with TEER, including Lactobacillus and Bifidobacterium taxa. Thirty-six taxa were associated with tight junction protein expression, including Lactobacillus and Bifidobacterium. DISCUSSION: Compensated cirrhosis is characterized by increased duodenal epithelial permeability with a distinct mucosal microbial community. Intriguingly, bacteria previously associated with health were protective of duodenal permeability.

[Early outcomes of excimer laser atherectomy for below-the-knee lesions in patients with diabetic foot].

Objective: To evaluate the clinical outcomes of excimer laser atherectomy (ELA) in the treatment of diabetic foot with below-the-knee(BTK) lesions. Methods: The clinical data of 11 patients with diabetic foot with BTK lesions who underwent ELA at Department of Vascular Surgery,Zhongshan Hospital of Fudan University and Department of Vascular and Wound Treatment Center,Jinshan Hospital of Fudan University from September 2019 to May 2021 were retrospectively analyzed.There were 10 males and 1 female,aged 70.5 years(range:41 to 83 years).There were 20 lesions in 12 limbs,including 19 chronic total occlusion.All of the limbs were classified as Rutherford class 5 and suffered ulceration.The surgical efficacy,complications and ankle brachial index(ABI) after operation were record. Results: All patients underwent the operation successfully,the technical success rate was 12/12.No distal embolization,flow-limiting dissection,perforation or bailout stenting was occurred.The follow-up period was 8.2 months(range:3 to 13 months).The ABI increased from 0.58(range:0.24 to 1.57) before operation to 0.88(range:0.68 to 1.05) after operation.At 3 months after the operation,1 limb (1/12) underwent endovascular operation again due to restenosis,ulcers were healed in 5 limbs(5/12),and no amputation (limb/toe),death or loss of follow-up patients.Six months after the operation,2 patients were lost to follow-up and 2 died,ulcers were healed in 6 limbs(6/8),1 limb (1/8) underwent toe amputation due to prolonged healing of ulcers of toe. Conclusion: ELA is feasible and effective in the treatment of DF with BTK lesions,providing a new option of debulking atherectomy in such a group of patients.

Changes in the Management of Patients having Radical Radiotherapy for Lung Cancer during the First Wave of the COVID-19 Pandemic in the UK.

AIMS: In response to the COVID-19 pandemic, guidelines on reduced fractionation for patients treated with curative-intent radiotherapy were published, aimed at reducing the number of hospital attendances and potential exposure of vulnerable patients to minimise the risk of COVID-19 infection. We describe the changes that took place in the management of patients with stage I-III lung cancer from April to October 2020. MATERIALS AND METHODS: Lung Radiotherapy during the COVID-19 Pandemic (COVID-RT Lung) is a prospective multicentre UK cohort study. The inclusion criteria were: patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between 2nd April and 2nd October 2020. Patients who had had a change in their management and those who continued with standard management were included. Data on demographics, COVID-19 diagnosis, diagnostic work-up, radiotherapy and systemic treatment were collected and reported as counts and percentages. Patient characteristics associated with a change in treatment were analysed using multivariable binary logistic regression. RESULTS: In total, 1553 patients were included (median age 72 years, 49% female); 93 (12%) had a change to their diagnostic investigation and 528 (34%) had a change to their treatment from their centre's standard of care as a result of the COVID-19 pandemic. Age ≥70 years, male gender and stage III disease were associated with a change in treatment on multivariable analysis. Patients who had their treatment changed had a median of 15 fractions of radiotherapy compared with a median of 20 fractions in those who did not have their treatment changed. Low rates of COVID-19 infection were seen during or after radiotherapy, with only 21 patients (1.4%) developing the disease. CONCLUSIONS: The COVID-19 pandemic resulted in changes to patient treatment in line with national recommendations. The main change was an increase in hypofractionation. Further work is ongoing to analyse the impact of these changes on patient outcomes.

[Relationship of C1QA level and therapeutic effect and prognosis of DLBCL patients treated with R-CHOP].

Objective: To investigate the relationship between plasma levels of complements before treatment and the clinicopathological feathers and prognoses of diffuse large B-cell lymphoma (DLBCL) patients treated with Rituximab (R)-CHOP or R-CHOP-like therapy. Methods: The clinicopathological data of 105 DLBCL patients treated in cancer Hospital of Chinese Academy of Medical Sciences from 2010 to 2016 were collected. The plasma samples from 105 DLBCL patients treated with R-CHOP or R-CHOP-like therapy and 80 healthy controls were used to detect 34 complement levels before treatment by utilizing antibody microarray. The relationship between plasma levels of complements and the clinicopathological feathers and prognosis of DLBCL patients were analyzed. Results: The signal values of C1QA and CR1L in patients with international prognostic index (IPI) scores of 3-5 were 1 261.43±138.9 and 2 214.69±98.58, respectively, higher than 950.79±80.19 and 984.67±121.79 in patients with IPI scores of 0~2 (both P<0.05). The levels of C1QA and CR1L in the non-complete response (CR) group were 1 165.43±98.56 and 2 263.13±145.63, respectively, higher than 914.70±100.77 and 1 821.34±84.68 in the CR group (both P<0.05). Cox regression analysis showed that elevated C1QA signal value was associated with poor progression-free survival (PFS) and poor overall survival (OS) (PFS: HR=2.063, 95%CI: 1.220-3.489, P=0.007; OS: HR=2.23, 95%CI: 1.036~4.798, P=0.040). After IPI correction by Cox multivariate model, the elevated C1QA signal value was still correlated with poor PFS (HR=1.765, 95%CI 1.034~3.013, P=0.037). Conclusions: The baseline plasma levels of C1QA and CR1L are correlated with IPI scores and therapeutic effects of DLBCL patients treated with R-CHOP. The baseline plasma level of C1QA has a certain predictive value for the prognostic evaluation of DLBCL.

[Biomechanical study of anterior occipital condyle screw plate system].

Objective: To analyze the feasibility of anterior occipitocervical fusion biomechanical characteristic of craniovertebral reconstruction by anterior occipital condyle screw plate system. Methods: Six cervical vertebra specimens including 4 males and 2 females were enrolled, whose mean age of death was (49.3±7.5) years. The normal models were established by soft tissue dissection, and the instability models were established by destroy bone and ligament structure including, anterior arch of the atlas, part of the lateral mass of the atlas, the odontoid process, the odontoid apical ligament, the pterygoid ligament, the transverse ligament of the atlas the joint capsule. The clivus screw fixation models were established by anterior clivus screw fixation, and then those models were performed by anterior occipital condyle screw fixation. All four groups were loaded with a 1.5 N·m continuous pure force in flexion-extension, lateral bending, and axial rotation. Then measured the range of motion of specimen C0-C1 and C0-C2. And the pull-out force test was conducted to compare the effects of unicortical and bicortical fixation on the pull-out force of screws. Results: In the C0-C1 segment, the range of motion in flexion-extension (forward and posterior), lateral bending and axial rotation in the clivus group was 6.46°±0.85°, 5.14°±0.76°, 2.73°±0.36°, 1.12°±0.41°, respectively; and it was 5.92°±0.90°, 4.16°±1.06°, 2.86°±0.50°, 1.05°±0.27°, respectively in the occipital condyle group. As for C0-C2 segment, the range of motion in the clivus group was 9.55°±1.99°, 10.46°±2.03°, 6.90°±1.29°, 13.51°±1.37°, respectively; and it was 8.14°±1.38°, 9.53°±1.55°, 4.75°±1.06°, 7.90°±1.68°, respectively, in the occipital condyle group. The ranges of motion in the occipital condyle group were significantly lower than clivus group (all P<0.05). The maximum pull out force by bicortical fixation was significantly better than unicortical fixation ((439±33) N vs (408±28) N, P<0.05). Conclusion: The anterior occipital condyle screw plate system provides better stability especially in anti-bending and anti-rotation than the anterior clival screw fixation.

[Digital and anatomical study of posterior atlantooccipital joint-occipital condyle-clivus screw technique].

Objective: To investigate the screw placement parameters, feasibility and safety of posterior atlantooccipital joint-occipital condyle-clivus screw technique in Chinese people. Methods: Upper cervical spine CT images of 46 patients, including 24 males and 22 females, were collected with random number table from June 2019 to May 2020 in Ningbo No.6 Hospital. The patients aged 20-55 years, with a mean age of (39±9) years. Total of 92 sides of upper cervical spine models were obtained by Mimics 19.0 digital three-dimensional reconstruction, and screw placement was conducted simulately. The midpoint of transition zone between the posterior arch of atlas and the inferior articular process of lateral mass was selected as the screw entry point. The diameter and length of screws was 3.5 mm and 50 mm, respectively. Detailed morphometric measurements of the 92 atlantooccipital joint-occipital condyle-clivus screws were conducted. The distance between the screw and its surrounding important structures, screw inside and upper tilting angles, the length of screw trajectory in atlas and the length of screw trajectory on occipital side (occipital condyle-clivus) were all measured. Paired t test was performed on the parameters of left and right screw placement to confirm whether there was difference between the two sides. Results: In the 46 cases of upper cervical spine digital three-dimensional models, 92 posterior atlantooccipital joint-occipital condyle-clivus screws were implanted. All the screws were completely fixed in the clivus, without breaking through the upper sphenoid sinus, entering into the canalis spinalis and foramen magnum, and damaging the surrounding structures such as hypoglossal canal. The screw trajectory parameters between the left and right sides were slightly different, but there was no statistical differences between the two sides (P>0.05). The vertical distance between the screw entry point and the upper edge of atlas was (12.6±1.0) mm, the vertical distance between the screw entry point and the lower edge of atlas was (6.5±0.6) mm, the distance between the screw and the medial border of atlas vertebral artery foramen was (6.7±0.6) mm, the distance between the screw entry point and the medial wall of atlas was (6.6±0.7) mm, the distance between the screw outer margin and the hypoglossal canal was (5.5±0.6) mm, screw inside tilting angle was 21.2°±2.5°, screw upper tilting angle was 52.0°±3.4°, the length of screw trajectory in atlas was (12.1±0.9) mm, the length of screw trajectory on occipital side (occipital condyle-clivus) was (37.9±0.9) mm. Conclusion: The posterior atlantooccipital joint-occipital condyle-clivus screw technique can serve as a feasible and safe treatment for instability of the occipitocervical junction, which can be used as a new posterior occipitocervical fusion technique.

Abnormalities of the default-mode network homogeneity and executive dysfunction in people with first-episode, treatment-naive left temporal lobe epilepsy.

OBJECTIVE: Converging evidence has demonstrated that there is aberrant connectivity of the default-mode network (DMN) in left temporal lobe epilepsy (lTLE) yet changes in the network homogeneity (NH) of the DMN in people with first-episode, treatment-naive lTLE remains unclear. In this study, we used an NH method to investigate the NH of the DMN in people with first-episode, treatment-naive, lTLE, at rest. PATIENTS AND METHODS: We collected resting-state functional magnetic resonance imaging (rs-fMRI), and attention network test (ANT) data from 43 people with lTLE and 42well-matched, healthy control subjects. An NH approach was used to analyze the data. RESULTS: People with lTLE have decreased NH in the right inferior temporal gyrus (ITG) and the left middle temporal lobe (MTG), and increased NH in the bilateral precuneus (PCu) and right inferior parietal lobe (IPL), as compared with the controls. We also found that people with lTLE had a longer executive control reaction time (RT). No significant correlations were found between abnormal NH values and clinical variables in the subjects. CONCLUSIONS: These findings suggest that abnormal NH of the DMN exists in lTLE subjects and highlight the significance of the DMN in the pathophysiology of cognitive problems occurring in lTLE.

Linoleic acid and α-linolenic acid inhibit conjugative transfer of an IncX4 plasmid carrying mcr-1.

AIMS: The aim of this study was to determine the effects of unsaturated fatty acids on clinical plasmids. METHODS AND RESULTS: Two unsaturated fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) at final concentration 0, 0·03, 0·3 and 3 mmol l-1 , respectively, were used to assess the effects on conjugative transfer of a mcr-1-harbouring plasmid pCSZ4 (IncX4) in conjugation experiment. The inhibitory mechanisms were analysed by molecular docking and the gene expression of virB11 was quantitated by qRT-PCR. Target plasmid diversity was carried out by TrwD/VirB11 homology protein sequence prediction analysis. Our results showed that LA and ALA inhibit plasmid pCSZ4 transfer by binding to the amino acid residues (Phe124 and Thr125) of VirB11 with dose-dependent effects. The expression levels of virB11 gene were also significantly inhibited by LA and ALA treatment. Protein homology analysis revealed a wide distribution of TrwD/VirB11-like genes among over 37 classes of plasmids originated from both Gram-negative and Gram-positive bacteria. CONCLUSIONS: This study demonstrates representing a diversity of plasmids that may be potentially inhibited by unsaturated fatty acids. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work reported here provides additional support for application of curbing the spread of multiple plasmids by unsaturated fatty acids.

Correlations of hsa_circ_0046264 expression with onset, pathological stage and chemotherapy resistance of lung cancer.

OBJECTIVE: The purpose of this study was to investigate the correlations of hsa_circ_0046264 expression with the onset, pathological stage, and chemotherapy resistance of lung cancer. PATIENTS AND METHODS: Firstly, gene expression profiling microarrays were applied to screen the differentially expressed circular ribonucleic acids (circRNAs) in the tumor tissues of patients with non-small cell lung cancer (NSCLC). Secondly, quantitative Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) assay was adopted to further verify the circRNAs with significant differences. Thirdly, the correlations of hsa_circ_0046264 expression level with the clinical features of NSCLC patients were explored via statistical analysis. Fourthly, Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curve were utilized to investigate the influence of hsa_circ_0046264 expression level on the survival of the patients. Finally, the role of hsa_circ_0046264 in the process of lung cancer was probed using in vitro experimental methods. RESULTS: It was shown in the results of gene microarray assay that hsa_circ_0046264 was the most prominently upregulated gene, and RT-qPCR assay further proved that hsa_circ_0046264 expression was upregulated remarkably in the tissues of tumor patients. Clinical analysis indicated that the expression level of hsa_circ_0046264 was notably associated with the patient's age, tumor size, tumor-node-metastasis (TNM) stage, and lymph node metastasis (p<0.01). In addition, Kaplan-Meier statistical analysis manifested that the patients in hsa_circ_0046264 low-expression group had a markedly longer survival than those in hsa_circ_0046264 high-expression group. In the tumor tissues and serum of the patients, the area under ROC curve of hsa_circ_0046264 was 0.971 and 0.915, the specificity was 0.973 and 0.957, and the sensitivity was 0.951 and 0.927, while the Youden Index was 0.924 and 0.884 respectively. The results of Cell Counting Kit-8 (CCK-8) assay revealed that the proliferative ability of lung cancer A549 cells was significantly enhanced at 36, 48, and 72 h in hsa_circ_0046264 overexpression group. According to the results of wound-healing assay, the migratory ability of A549 cells was distinctly strengthened in hsa_circ_0046264 overexpression group compared with that in the control group (p<0.05). Moreover, the transwell assay results pointed out that the invasive ability of A549 cell lines at 48 h after overexpression of hsa_circ_0046264 was evidently stronger than that in control group (p<0.05). Under the stimulation of different doses of cisplatin, hsa_circ_0046264 overexpression group had a clearly raised survival rate of A549 cells in comparison with control group, and the differences in data were statistically significant (p<0.01). CONCLUSIONS: Hsa_circ_0046264 may serve as a potential biomarker for the diagnosis and prognosis and a possible therapeutic target of lung cancer.

[Analysis of asymmetric hearing loss in both ears of patients with occupational noise-induced deafness].

Objective: To investigate the characteristics of asymmetric hearing loss in left and right ears of patients with occupational noise-induced deafness and to explore the possible causes of asymmetric hearing loss. Methods: A total of 423 cases of occupational noise-induced deafness diagnosed in Guangdong Province Hospital for Occupational Disease Prevention and Treatment from May 2015 to May 2018 were investigated retrospectively. On the basis of three consecutive pure tone audiometry (PTA) with intervals of more than 3 d in hospital, the minimum of hearing threshold of each frequency and the frequency response threshold of auditory steady-state response (ASSR) , and based on the GBZ 49-2014 "Diagnosis of Occupational Noise-induced Deafness". The statistical analysis of Wilcoxon signed rank test and Spearman correlation analysis were carried out by nonparametric test. The hearing threshold weight of PTA and the response threshold of ASSR were tested and compared from different dimensions according to sex, age, length of service of exposure noise, diagnosis grade and so on. Results: There were 369 male (87.23%) and 54 female (12.77%) ; the age was (41.8±7.6) years; the length of service was (10.1±6.2) years. The weighted values of left ear PTA and ASSR were higher than those of right ear (P<0.001) . The weighted values of left ear PTA and ASSR were higher than those of right ear (P<0.05) in men, patients with age ≤ 40 and 41-60 years, 3-9 years of service, and patients with mild grade (P<0.05) . After the equalization of characteristic variables, the weighted values of left ear PTA and ASSR were also higher than those of right ear (P<0.05) . There was a positive correlation between the weighted value of PTA and the weighted value of ASSR (P<0.001) . Conclusion: There is asymmetry in hearing loss of patients with occupational noise deafness, and hearing loss in the left ear is higher than that in the right ear.

[The outcome and safety of neoadjuvant PD-1 blockade plus chemotherapy in stage â ¡~â ¢ non-small cell lung cancer].

Objective: To explore the safety and therapeutic effect of programmed death 1 (PD-1) antibody combined with chemotherapy as a neoadjuvant therapy for patients with stage Ⅱ to Ⅲ non-small cell lung cancer (NSCLC). Methods: Thirteen patients, who had been diagnosed as stage Ⅱ-Ⅲ NSCLC and received PD-1 inhibitor plus chemotherapy as a neoadjuvant treatment in National Cancer Center/Cancer Hospital were recruited. The patients received consecutive neoadjuvant chemotherapy for 21 days as a cycle and the therapeutic efficacy was evaluated after two cycles. Results: At the last time of follow-up on December 2, 2019, the objective response rate (ORR) and disease control rate (DCR) of these patients were 61.5% (95% CI 30.9%-92.1%) and 100%, respectively. The downregulation rate of disease stage was 61.5% (8/13). The resectable rate was 38.5% (5/13), among them, the major pathologic response (MPR) was 60.0% (3/5) and the complete pathologic response (CPR) was 20.0% (1/5). The neoadjuvant chemotherapy displayed a low incidence of adverse reaction. The main grade 3 to 4 toxicities were neutropenia (38.5%) and leukopenia (23.1%). There was no significant immune-related toxicity. The safety and tolerability of perioperative period of patients underwent resection were promising. Conclusions: Immunotherapy combined with chemotherapy as a neoadjuvant treatment is an effective, low-toxicity treatment manner, which has perioperative safety and high rate of MPR for patients with resectable NSCLC. It is a promising treatment option for patients with stage Ⅱ to Ⅲ NSCLC.