Familial rare EGFR-mutant lung cancer syndrome: Review of literature and description of R776H family.

BACKGROUND: Interest in hereditary lung cancer is increasing, in particular germline mutations in the Epidermal Growth Factor Receptor (EGFR) gene. We review the current literature on this topic, discuss risk of developing lung cancer, treatment and screening options and describe a family of 3 sisters with lung cancer and their unaffected mother all with a rare EGFR germline mutation (EGFR p.R776H). METHODS: We searched PubMed, Medline, Embase, the Cochrane Library, Google Scholar and scanned reference lists of articles. Search terms included "EGFR germline" and "familial lung cancer" or "EGFR familial lung cancer". We also describe our experience of managing a family with rare germline EGFR mutant lung cancer. RESULTS: Although the numbers are small, the described cases in the literature show several similarities. The patients are younger and usually have no or light smoking history. 50% of the patients were treated with a tyrosine kinase inhibitor (TKIs) with OS over six months. CONCLUSION: Although rare, germline p.R776H EGFR lung cancer mutations are over-represented in light or never smoking female patients who often also possess an additional somatic EGFR mutation. Treatment with TKIs appears suitable but further research is needed into the appropriate screening regime for unaffected carriers or light/never smokers.

Added value of spectral computed tomography quantitative parameters for differentiating tuberculosis-associated fibrosing mediastinitis from endobronchial lung cancer: initial results.

OBJECTIVE: The objective of this study was to explore the added value of spectral computed tomography (CT) parameters to conventional CT features for differentiating tuberculosis-associated fibrosing mediastinitis (TB-associated FM) from endobronchial lung cancer (EBLC). METHODS: Chest spectral CT enhancement images from 109 patients with atelectasis were analyzed retrospectively. These patients were divided into two distinct categories: the TB-associated FM group (n = 77) and the EBLC group (n = 32), based on bronchoscopy and/or pathological findings. The selection of spectrum parameters was optimized with the least absolute shrinkage and selection operator regression analysis. The relationship between the spectrum parameters and conventional parameters was explored using Pearson's correlation. Multivariate logistic regression analysis was used to build spectrum model. The spectrum parameters in the spectrum model were replaced with their corresponding conventional parameters to build the conventional model. Diagnostic performances were evaluated using receiver operating characteristic curve analyses. RESULTS: There was a moderate correlation between the parameters ㏒(L-AEFNIC) - ㏒(L-AEFC) (r= 0.419; p< 0.0001), ㏒(O-AEF40KeV) - ㏒(O-AEFC) (r= 0.475; p< 0.0001), [L-A-hydroxyapatite {HAP}(I)] - (L-U-CT) (r= 0.604; p< 0.0001), {arterial enhancement fraction (AEF) derived from normalized iodine concentration (NIC) of lymph node (L-AEFNIC), AEF derived from CT40KeV of bronchial obstruction (O-AEF40KeV), arterial-phase Hydroxyapatite (Iodine) concentration of lymph node [L-A-HAP(I)], AEF derived from conventional CT (AEFC), unenhanced CT value (U-CT)}. Spectrum model could improve diagnostic performances compared to conventional model (area under curve: 0.965 vs 0.916, p= 0.038). CONCLUSION: There was a moderate correlation between spectrum parameters and conventional parameters. Integrating conventional CT features with spectrum parameters could further improve the ability in differentiating TB-associated FM from EBLC.

[Changes in OCTA-related parameters and their impact on retinal sensitivity after ILM flap inversion surgery in patients with IMH].

Objective: To analyze the changes in optical coherence tomography angiography(OCTA)-related parameters before and after idiopathic macular hole (IMH) internal limiting membrane (ILM) flap inversion surgery and assess their impact on retinal sensitivity. Methods: A retrospective case series study was conducted, collecting clinical data of 30 patients (30 eyes) diagnosed with IMH who underwent vitrectomy combined with ILM flap inversion surgery at Shanxi Eye Hospital, affiliated with Shanxi Medical University, between January 2020 and December 2021. Visual acuity and best-corrected visual acuity were examined preoperatively and at 1, 3, and 6 months postoperatively. Microperimetry measured retinal sensitivity (RS), and OCTA measured retinal thickness (RT) as well as vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Statistical analysis was performed using t-tests, repeated measures analysis of variance, and Pearson correlation analysis. Results: Thirty patients with IMH (30 eyes) were included, with 3 males (3 eyes) and 27 females (27 eyes). The mean age was (62.5±3.0) years, and the follow-up time was (96.3±1.3) days, with a 100% closure rate of macular holes postoperatively. RT in the macular was significantly lower at 1, 3, and 6 months postoperatively compared to preoperative values (F=46.21, P<0.001). The RT in the upper macular region showed statistically significant differences at different time points (P<0.001). VD in the SCP layer showed no significant differences between the upper and lower macular regions at various time points (F=3.21, P=0.601). VD in the upper region of the DCP layer increased at 1, 3, and 6 months postoperatively (P<0.001). RS in the macular was higher at 1, 3, and 6 months postoperatively compared to preoperative values (F=52.01, P<0.001). RS in the lower macular region increased at 3 and 6 months postoperatively (P<0.001), while in the upper region, it increased only at 6 months postoperatively (P<0.001). There was a positive correlation between RS and RT at 1 and 3 months postoperatively, but not at 6 months postoperatively in the upper macular region (r=0.40, P=0.071). In the lower macular region, there was a positive correlation between RS and RT at 1 and 3 months postoperatively (P<0.001). There was no correlation between RS in the upper macular region at 6 months postoperatively and preoperative RT (r=0.43, P=0.072), but there was a positive correlation with RT at 3 months postoperatively (r=0.58, P=0.041). Conclusions: After idiopathic macular hole internal limiting membrane flap inversion surgery, the OCTA-related parameters have changed. There are transient changes in deep vascular parameters and thinning of the retinal layers at the ILM inversion site, leading to decreased sensitivity.

Predictive effect of net water uptake on futile recanalisation in patients with acute large-vessel occlusion stroke.

AIM: To determine whether net water uptake (NWU) based on automated software evaluation could predict futile recanalisation in patients with acute anterior circulation large-vessel occlusion (LVO). MATERIALS AND METHODS: Patients with acute anterior circulation LVO undergoing mechanical thrombectomy in Jinling Hospital were evaluated retrospectively. NWU and other baseline data were evaluated by performing univariate and multivariate analyses. The primary endpoint was 90-day modified Rankin scale score ≥3. A nomogram to predict poor clinical outcomes was developed based on multivariate logistic regression analysis. RESULTS: Overall, 135 patients who underwent thrombectomy with a TICI grade ≥2b were enrolled. In multivariate logistic regression analysis, the following factors were identified as independent predictors of futile recanalisation: age (odds ratio [OR]: 1.055, 95 % confidence interval [CI]: 1.004-1.110, p=0.035), female (OR: 0.289, 95 % CI: 0.098-0.850, p=0.024), hypertension (OR: 3.182, 95 % CI: 1.160-8.728, p=0.025), high blood glucose level (OR: 1.36, 95 % CI: 1.087-1.701, p=0.007), admission National Institutes of Health Stroke Scale score (OR: 1.082, 95 % CI: 1.003-1.168, p=0.043), and NWU (OR: 1.312, 95 % CI: 1.038-1.659, p=0.023). CONCLUSIONS: NWU based on Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS) could be used to predict the occurrence of futile recanalisation in patients with acute anterior circulation LVO ischaemic stroke.

Predicting subsolid pulmonary nodules before percutaneous needle biopsy: a comparison of artificial neural network and biopsy results.

AIM: To establish an artificial neural network (ANN) model to predict subsolid nodules (SSNs) before percutaneous core-needle biopsy (PCNB). The results of the two methods were compared to provide guidance on the treatment of SSNs. MATERIALS AND METHODS: This was a single-centre retrospective study using data from 1,459 SSNs between 2013 and 2021. The ANN was developed using data from patients who underwent surgery following computed tomography (CT) (SFC) and validated using data from patients who underwent surgery following biopsy (SFB). The prediction results of the ANN for the PCNB group and the histopathological results obtained after biopsy were compared with the histopathological results of lung nodules in the same group after surgery. Additionally, the choice of predictors for PCNB was analysed using multivariate analysis. RESULTS: There was no significant difference between the accuracies of the ANN and PCNB in the SFB group (p=0.086). The sensitivity of PCNB was lower than that of the ANN (p=0.000), but the specificity was higher (p=0.001). PCNB had better diagnostic ability than the ANN. The incidence of precursor lesions and non-neoplastic lesions in the SFB group was lower than that in the SFC group (p=0.000). A history of malignant tumours, size (2-3 cm), volume (>400 cm3) and mean CT value (≥-450 HU) are important factors for selecting PCNB. CONCLUSIONS: Both ANN and PCNB have comparable accuracy in diagnosing SSNs; however, PCNB has a slightly higher diagnostic ability than ANN. Selecting appropriate patients for PCNB is important for maximising the benefit to SSN patients.

[The efficacy analysis of neurosurgical robot-assisted DBS in the treatment of elderly Parkinson's disease].

Objective: To investigate the surgical efficacy of neurosurgery robot deep brain stimulation(DBS) in the treatment of elderly Parkinson's disease(PD). Methods: The clinical data of elderly patients (≥75 years) with PD who underwent neurosurgical robot-assisted DBS surgery in the Department of Neurosurgery of the General Hospital of Northern Theater Command from September 2016 to September 2022 were collected retrospectively. Operation time, electrode implantation duration, postoperative pneumocephalus volume, electrode implantation accuracy, the Tao's DBS surgery scale, perioperative complications were analyzed.The unified Parkinson's disease rating scales (UPDRS), UPDRS-Ⅲ, tremor, rigidity, bradykinesia, axial, Barthel Activities of Daily Living (ADL-Barthel), Levodopa Equivalent Daily Dose (LEDD), Montreal Cognitive Assessment (MoCA), Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores and mortality were assessed respectively before operation, 6, 12 and 24 months after operation and last follow-up. Results: A total of 25 elderly patients were enrolled, including 14 males and 11 females, aged(78.3±3.2) years. Nine patients had underlying diseases. Nine patients (36%) underwent bilateral Globus Pallidus pars Interna deep brain stimulation (GPi-DBS) and 16 patients (64%) underwent bilateral subthalamic nucleus deep brain stimulation (STN-DBS).The operation time was (1.56±0.19) hours, the electrode implantation duration was (1.01±0.19) hours, the pneumocephalus volume was 9.8(4.7, 23.3) cm3, and the electrode implantation accuracy was (0.84±0.24) mm, the Tao's DBS surgery scale was (80.2±6.2).The follow-up time [M(Q1, Q3)] was 57.3(27.9, 75.7) months. No serious complications such as intracranial hemorrhage, infection or poor wound healing occurred during the perioperative period. The improvement rate of UPDRS, UPDRS-Ⅲ, rigidity, bradykinesia, and LEDD at 6 months after surgery was significantly higher than that at 24 months after surgery and at the last follow-up (all P<0.05); the improvement rate of axial symptoms, ADL-Barthel score, and MoCA score at 6 months after surgery was significantly higher than that at the last follow-up (P<0.05). HAMD and HAMA scores showed no significant improvement during follow-up after surgery (both P>0.05). At the last follow-up, 12 patients died, with death time of (35.1±20.2) months after operation, and the death age of [M(Q1, Q3)] 80(79, 83)years. Conclusions: Robot-assisted DBS surgery for elderly patients with PD is accurate and safe, and the postoperative symptoms are significantly improved, and they can benefit from neuromodulation for long term, and the risks are controllable.

Lateral Intraventricular Epidermoid Cyst: A Case Report and Literature Review.

Epidermoid cysts originate from ectopic embryonic epithelial cells and are a very common type of benign intracranial tumor. However, the incidence of intraventricular epidermoid cysts is low, and lateral intraventricular epidermoid cysts are even rarer. Here, we present a case of lateral intraventricular epidermoid cyst and review the relevant literature. A 54-year-old female complained of recurrent headaches over a 5-year period, with aggravated symptoms during the last 2 months or more. A computed tomography of the brain showed a low-density mass in the lateral ventricle and enlargement of the right ventricle. Cranial magnetic resonance imaging further confirmed that the mass was an epidermoid cyst. The patient underwent microscopic surgical resection combined with endoscopy using an interhemispheric craniotomy approach. The mass was satisfactorily removed, and the patient recovered well. Lateral intraventricular epidermoid cysts often present with clinical symptoms due to the invasion of surrounding brain tissue or blockage of the cerebrospinal fluid system. Diagnosis relies on examination by magnetic resonance imaging, and treatment relies on surgical resection. The prognoses of patients are mostly excellent and depend on whether the tumor is resected cleanly or not.

Association between Dried Fruit Intake and DNA Methylation: A Multivariable Mendelian Randomization Analysis.

OBJECTIVES: Observational studies have reported associations between dried fruit intake and DNA methylation(DNAm). However, inherent flaws in observational study designs make them susceptible to confounding and reverse causality bias. Consequently, it is unclear whether a causal association exists. In the present study, we aimed to investigate the causal associations between dried fruit intake and DNAm. METHODS: We performed two-sample Mendelian randomization (MR) using the IEU Open GWAS database aggregated data. Forty-three single nucleotide polymorphisms (SNPs) associated with dried fruit intake as instrumental variables (IVs) were selected as exposure. DNAm outcomes include Gran (estimated granulocyte proportions); AgeAccelGrim(GrimAge acceleration); Hannum (Hannum age acceleration); IEAA(Intrinsic epigenetic age acceleration), AgeAccelPheno( PhenoAge acceleration), and DNAmPAIadjAge (DNAm-estimated plasminogen activator inhibitor-1 levels). We used the MR pleiotropy residual sum and outlier test (MRPRESSO) and Radial-MR test to identify any level of multi-effect outliers and assessed the causal effect estimates(after removing outliers). The primary causal effects were estimated using inverse-variance weighted (IVW) method and undertook sensitivity analyses using MR methods robust to horizontal pleiotropy.The direct effects of dried fruit intake on DNAm were estimated using multivariable mendelian randomization (MVMR). RESULTS: Leveraging two-sample MR analysis, we observed statistically significant associations between dried fruit intake with a lower AgeAccelGrim(ß=-1.365, 95% confidence intervals [CI] -2.266 to -0.464, PIVW=2.985×10-3) and AgeAccelPheno (ß= -1.933, 95% CI -3.068 to -0.798, PIVW=8.371×10-4). By contrast, the effects level on Gran (ß=0.008, PIVW=0.430), Hannum(ß=-0.430, PIVW=0.357), IEAA(ß=-0.184, PIVW=0.700), and DNAmPAIadjAge (ß=-1.861, PIVW=0.093) were not statistically significant. MVMR results adjusting for the potential effects of confounders showed that the causal relationship between dried fruit intake and AgeAccelGrim(ß= -1.315, 95% CI -2.373 to -0.258, PIVW=1.480×10-2) and AgeAccelPheno(ß= -1.595, 95% CI -2.987 to -0.202, PIVW=2.483×10-2) persisted. No significant horizontal polymorphism was found in the sensitivity analysis. CONCLUSION: Our MR study suggested that increased dried fruit intake is associated with slower AgeAccelGrim and AgeAccelPheno. It can providing a promising avenue for exploring the beneficial effects of dried fruit intake on lifespan extension.

[A study on the arthroscopic temporomandibular joint disc reduction on the outcome of orthodontic patients with anterior disc displacement without reduction].

Objective: To investigate the arthroscopic temporomandibular joint disc reduction on the outcome of orthodontic patients with anterior disc displacement without reduction. Methods: From January 2012 to December 2021, forty treated orthodontic patients with anterior disc displacement without reduction (unilateral/bilateral) and no obvious articular cartilage absorption were selected from Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The patients were (17.5±3.8) years old (12-25 years old), including 8 males and 32 females. Twenty patients who had completed arthroscopic temporomandibular joint disc reduction were included in the control group, and twenty patients with untreated temporomandibular joint disc were included in the experimental group. Model measurement (including overjet, etc.), cephalometric analysis (including ANB angle, which was formed by subspinale, nasion and supramental, etc.) and temporomandibular joint magnetic resonance imaging (including measurement of the condyle height of the displacement sides) were used to compare the difference of two groups. Objective grading system was used to evaluate the efficacy of orthodontic treatment. Results: The overjet of the experimental group and the control group after orthodontic treatment was (2.19±0.76) and (1.92±0.94) mm, respectively. Both two groups achieved ideal overjet with no statistical difference (t=1.02, P=0.314). The ANB angle difference before and after treatment in the control group (-1.97°±2.87°) was greater than that in the experimental group (0.09°±1.82°), and the difference was statistically significant (t=2.72, P=0.010). The variation of condyle height before and after treatment was (0.30±1.11) mm in the experimental group and (0.82±1.25) mm in the control group, with no statistical significance (t=1.80, P=0.076). The post-treatment objective grading system scores of the experimental group and the control group were 21.00 (16.00, 24.00) and 21.00 (17.00, 25.00), respectively, which had no statistical difference (U=0.24, P=0.808). Conclusions: In orthodontic patients with anterior disc displacement without reduction and no obvious articular cartilage absorption, whether displaced discs are repositioned after arthroscopic surgery has no significant effect on the orthodontic treatment outcome.

[Influence of muscle energy technology combined with Maitland joint mobilization surgery on the elbow joint flexion function in patients with deep burn of elbow joint].

Objective: To investigate the influence of muscle energy technology (MET) combined with Maitland joint mobilization surgery on the elbow joint flexion function in patients with deep burn of elbow joint. Methods: A retrospective controlled clinical trial was conducted. From January 2020 to January 2022, 53 patients with elbow joint flexion dysfunction after deep burns who met the inclusion criteria were treated in Tongren Hospital of Wuhan University & Wuhan Third Hospital, including 32 males and 21 females, aged (37±12) years. According to the treatment method used, the patients were divided into conventional treatment alone group (15 cases), conventional treatment+joint mobilization surgery group (18 cases), and conventional treatment+joint mobilization surgery+MET group (20 cases). Before treatment and 2 months after treatment, the patient's elbow joint range of motion was measured using a protractor, the Mayo elbow joint function score was used to evaluate elbow joint function, a portable muscle strength tester was used to measure elbow extensor muscle strength, and visual analogue scale was used to evaluate pain degree. Data were statistically analyzed with one-way analysis of variance, least significant difference test, paired sample t test, Kruskal-Wallis H test, Wilcoxon signed rank-sum test, chi-square test, Fisher's exact probability test, and Bonferroni correction. Results: After two months of treatment, the elbow joint range of motion and elbow joint function scores of patients in conventional treatment+joint mobilization surgery group and conventional treatment+joint mobilization surgery+MET group ((103±12)° and 60 (50, 66), (131±14)° and 73 (65, 80)) were significantly larger and higher than those in conventional treatment alone group ((77±15)° and 45 (35, 50), P values all <0.05), respectively. The elbow joint range of motion and elbow joint function scores of patients in conventional treatment+joint mobilization surgery+MET group were significantly larger and higher than those in conventional treatment+joint mobilization surgery group (P values all <0.05), respectively. After two months of treatment, the elbow extensor muscle strength and pain score of patients in conventional treatment+joint mobilization surgery+MET group were respectively significantly larger and lower than those in conventional treatment alone group and conventional treatment+joint mobilization surgery group (P values all <0.05). The elbow extensor muscle strength and pain score of patients in conventional treatment+joint mobilization surgery group were similar to those in conventional treatment alone group (P>0.05). The elbow joint range of motion and elbow extensor muscle strength (with t values of 9.37, 25.54, 28.71, 6.70, 7.20, and 7.01, respectively, P<0.05), elbow joint function scores and pain scores (with Z values of 3.15, 3.63, 3.93, 3.30, 3.52, and 3.84, respectively, P<0.05) of patients in conventional treatment alone group, conventional treatment+joint mobilization surgery group, and conventional treatment+joint mobilization surgery+MET group after two months of treatment were significantly improved compared with those before treatment. Conclusions: The combination of MET and Maitland joint mobilization surgery can effectively improve elbow joint range of motion, elbow joint function, elbow extensor muscle strength, and pain of patients with deep elbow joint burns, therefore it is worthy of promotion.

[The consistency of skeletal muscle mass measured by CT at L1 and L3 levels and the correlation of skeletal muscle density at L1 level with prognosis in dialysis patients].

Objective: To investigate the consistency of skeletal muscle mass by CT at 1st lumbar vertebrae (L1) and 3rd lumbar vertebrae (L3) levels and the correlation of skeletal muscle density (SMD) at L1 level with prognosis in dialysis patients. Methods: A total of 1 020 patients who underwent initial dialysis and had CT examination data in four centers (Zhongda Hospital Affiliated to Southeast University, the Third Affiliated Hospital of Soochow University, Taizhou People's Hospital Affiliated to Nanjing Medical University and the Affiliated Hospital of Yangzhou University) from January 2014 to December 2019 were retrospectively collected. The skeletal muscle index (SMI) and SMD at L1 and L3 CT images were measured and calculated in patients with both L1 and L3 level CT images. The consistency of SMI and SMD at L1 and L3 levels was analyzed, and the cut-off value of SMI and SMD at L1 level for predicting all-cause mortality and their correlation with the prognosis of dialysis patients were studied. Cox regression model was used to analyze the risk factors for all-cause death and cardiac death. Results: A total of 383 patients had both L1 and L3 level images, including 233 males and 150 females. The average SMD value of 16 samples (4.2%) exceeded the 95% consistency limit range (-8.71 to 7.75 HU), and the average SMI value of 15 samples (3.9%) exceeded the 95% consistency limit range (-20.45 to 9.53 HU). The optimal cut-off value of SMD at L1 level for predicting all-cause mortality was 36.46 HU and the area under curve (AUC) of receiver operating characteristic (ROC) curve was 0.658 (95%CI: 0.596-0.721, P<0.001), with the sensitivity and specificity of 83.8% and 57.5%, respectively. SMI at L1 level was not significantly associated with all-cause mortality (P=0.299). Multivariate Cox regression analysis showed that low SMD at L1 level was associated with all-cause mortality (HR=2.861, 95%CI: 1.576-5.193, P=0.001) and cardiac death (HR=3.771, 95%CI:1.462-9.724, P=0.006). Conclusions: SMD at L1 levelis consistent with SMD at L3 level and can be used to evaluate muscle mass. Low SMD is a risk factor for mortality in dialysis patients.

Safety and efficacy of fortified antibiotics and fluoroquinolones for the treatment of bacterial keratitis: A meta-analysis.

PURPOSE: To compare the safety and efficacy of fortified antibiotics and fluoroquinolones in the treatment of bacterial keratitis. METHODS: PubMed, EMBASE, Cochrane Library, CNKI, Wanfang database and VIP database were systematically searched for randomized controlled trials (RCT) of treatment of bacterial keratitis with fortified antibiotics and fluoroquinolones. Rev Man 5.3 software was used to analyze outcome index cure rate, time to cure, and adverse events in a meta-analysis. RESULTS: After literature search and screening, 9 randomized controlled trials were included in this study. Compared with traditional fortified antibiotic therapy, fluoroquinolones show consistency in terms of cure rate and incidence of adverse events: cure rates (OR=0.99, 95% CI: 0.75, 1.30) and incidence of adverse events (OR=0.75, 95% CI: 0.48, 1.17). However, the time to cure for fluoroquinolones was shorter than that of fortified antibiotics (MD=0.96, 95% CI: 0.50, 1.41). CONCLUSION: The cure rate and safety of fluoroquinolones are equivalent to those of fortified antibiotics, so it seems reasonable to use fluoroquinolones as the preferred treatment for bacterial keratitis.

Impact of shift work on dementia: a systematic review and dose-response meta-analysis.

OBJECTIVES: Although shift work has been reported as having a link to dementia, evidence remains inconsistent, and a comprehensive dose-response meta-analysis of the association is still lacking. We therefore conducted this meta-analysis to explore the association between shift work and the risk of dementia. STUDY DESIGN: Systematic review and dose-response meta-analysis. METHODS: PubMed, Embase, and Web of Science databases were systematically searched. Fixed or random-effects models were used to estimate the summary relative risks (RRs) and 95% confidence intervals (95% CIs). Generalized least squares regression was used to estimate dose-response associations, and restricted cubic splines were used to examine possible linear or non-linear associations. RESULTS: Five articles (10 studies) with 72,999 participants and 23,067 cases were eventually included in the meta-analysis. The summary RRs and 95% CIs of dementia risk with shift work and night shift work versus daytime work were 1.13 (95% CI: 1.05-1.21, I2 = 46.70%) and 1.13 (95% CI: 1.03-1.24, I2 = 9.20%), respectively. The risk of dementia increased by 1% (RR = 1.01, 95% CI: 1.01-1.02, I2 = 41.3%) with each 1-year increase in the duration of shift work. We found a non-linear dose-response association between the duration of shift work and the risk of dementia (Pnon-linearity = 0.006). Though the shape of the curve was steeper with the duration of shift work <7 years, the increase was more gradual after 7 years. CONCLUSION: Our findings suggest that shift work may be a risk factor for future dementia and that controlling the length of shift work is a feasible measure that may contribute to prevent dementia.

Echocardiographic caudal vena cava measurements in healthy cats and in cats with congestive heart failure and non-cardiac causes of cavitary effusions.

BACKGROUND: Echocardiographic indices of the inferior vena cava have been associated with elevated right atrial pressures in humans. HYPOTHESIS/OBJECTIVES: Describe caudal vena caval (CVC) sonographic dimensions in healthy cats compared to cats with cardiogenic cavitary effusion (CCE), cardiogenic pulmonary edema (CPE), or non-cardiac causes of cavitary effusion (NCE). ANIMALS: 30 healthy control cats and 52 client-owned cats with CCE, CPE, or NCE examined at two university hospitals. METHODS: Sagittal 2-dimensional (2D) and M-mode CVC dimensions were acquired from the subxiphoid view. Caudal vena cava collapsibility index (CVC-CI) was calculated. Variables were compared between study groups using Kruskal-Wallis and Dunn's Bonferroni testing. Receiver operating characteristic curves were used to assess sensitivity and specificity for diagnostic categories. RESULTS: Healthy cats had sagittal 2D and M-mode (median, interquartile range) CVC maximal dimensions of 2.4 mm (1.3-4.0) and 3.4 mm (1.5-4.9) and CVC-CI of 52% (45.2-61.8) and 55% (47.8-61.3), respectively. The CVC maximal dimensions in healthy controls were smaller than in cats with cavitary effusions or pulmonary edema (all P<0.05). CVC-CI was different between CCE and NCE (P<0.0001) with cutoffs of CVC-CI ≤38% (2D) or ≤29% (M-mode) being 90.5% and 85.7% sensitive, and 94.4% and 100% specific for diagnosis of CCE, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Caudal vena cava measurements are larger in cats with cavitary effusions and cats with CPE than healthy cats. In cats with cavitary effusion, decreased CVC-CI, ≤38% (2D) or ≤29% (M-mode), was helpful in distinguishing between cardiogenic and noncardiogenic etiology.

Association of interleukin-6 and CD4+ T cells and two-week prognosis of patients with COVID-19: a predictive role.

OBJECTIVE: The aim of this study was to determine the association of inflammation and immune responses with the outcomes of patients at various stages, and to develop risk stratification for improving clinical practice and reducing mortality. PATIENTS AND METHODS: We included 77 patients with primary outcomes of either death or survival. Demographics, clinical features, comorbidities, and laboratory tests were compared. Linear, logistic, and Cox regression analyses were performed to determine prognostic factors. RESULTS: The average age was 59 years (35-87 years). There were 12 moderate cases (16.2%), 42 severe cases (54.5%), and 23 critical cases (29.9%); and 41 were male (53.2%). Until March 20, 68 cases were discharged (88.3%), and nine critically ill males (11.7%) died. Interleukin-6 (IL-6) levels on the 1st day were compared with IL-6 values on the 14th day in the severe and the critically ill surviving patients (F=4.90, p=0.034, ß=0.35, 95% CI: 0.00-0.10), and predicted death in the critically ill patients (p=0.028, ß=0.05, OR: 1.05, 95% CI: 1.01-1.10). CD4+ T-cell counts at admission decreased the hazard ratio of death (p=0.039, ß=-0.01, hazard ratio=0.99, 95% CI: 0.98-1.00, and median survival time 13.5 days). CONCLUSIONS: The present study demonstrated that IL-6 levels and CD4+ T-cell count at admission played key roles of predictors in the prognosis, especially for critically ill patients. High levels of IL-6 and impaired CD4+t cells are seen in severe and critically ill patients with COVID-19.

[Characteristics of lymph node metastasis of right recurrent laryngeal nerve in thoracic esophageal squamous cell carcinoma].

Objective: To understand the characteristics and influencing factors of lymph node metastasis of the right recurrent laryngeal nerve in thoracic esophageal squamous cell carcinoma (ESCC), and to explore the reasonable range of lymph node dissection and the value of right recurrent laryngeal nerve lymph node dissection. Methods: The clinicopathological data with thoracic ESCC were retrospectively analyzed, and the characteristics of lymph node metastasis along the right recurrent laryngeal nerve and its influencing factors were explored. Results: Eighty out of 516 patients had lymph node metastasis along the right recurrent laryngeal nerve, the metastasis rate was 15.5%. Among 80 patients with lymph node metastasis along the right recurrent laryngeal nerve, 25 cases had isolated metastasis to the right recurrent laryngeal nerve lymph node but no other lymph nodes. The incidence of isolated metastasis to the recurrent laryngeal nerve lymph node was 4.8% (25/516). A total of 1 127 lymph nodes along the right recurrent laryngeal nerve were dissected, 115 lymph nodes had metastasis, and the degree of lymph node metastasis was 10.2%. T stage, degree of tumor differentiation and tumor location were associated with right paraglottic nerve lymph node metastasis (all P<0.05). The lymph node metastasis rate along the right recurrent laryngeal in patients with upper thoracic squamous cell carcinoma (23.4%, 26/111) was higher than that of patients with middle (13.5%, 40/296) and lower (12.8%, 14/109) thoracic squamous cell carcinoma (P=0.033). In patients with poorly differentiated ESCC (20.6%, 37/180) the metastasis rate was higher than that of patients with moderately (14.6%, 39/267) and well-differentiated (5.8%, 4/69; P<0.05). The lymph node metastasis rate of patients with stage T4 (27.3%, 3/11) was higher than that of patients with stage T1 (9.6%, 19/198), T2 (19.0%, 16/84) and T3 (18.8%, 42/1 223; P<0.05). Multivariate regression analysis showed that tumor location (OR=0.61, 95% CI: 0.41-0.90, P=0.013), invasion depth (OR=1.46, 95% CI: 1.11-1.92, P=0.007), and differentiation degree (OR=1.67, 95% CI: 1.13-2.49, P=0.011) were independent risk factors for lymph node metastasis along right recurrent laryngeal nerve of ESCC. Conclusions: The lymph node along the right recurrent laryngeal nerve has a higher rate of metastasis and should be routinely dissected in patients with ESCC. Tumor location, tumor invasion depth, and differentiation degree are risk factors for lymph node metastasis along right recurrent laryngeal nerve in patients with ESCC.

[Anti-inflammatory mechanism of Balanophora involucrata: a network pharmacology and molecular docking-based analysis and verification in lipopolysaccharide-induced RAW264.7 cells].

OBJECTIVE: To investigate the main chemical constituents of Balanophora involucrata and the mechanism of its antiinflammatory effect based on network pharmacology and molecular docking technology. METHODS: Literature reports, Materia Medica, GeneCards and other databases were searched for anti-inflammatory compounds and their targets. String database and Cytoscape 3.7.2 software were used to obtain the protein-protein interaction (PPI) network and the drug-active ingredienttargets network and for GO and KEGG enrichment analyses. Molecular docking was performed using Auto Dock Tools 1.5.6. In an inflammatory RAW264.7 cell model induced by lipopolysaccharide (LPS), the effect of 25, 50, 100, 200 µg/mL Balanophora involucrata extract was tested on the production of inflammatory cytokines and phosphorylation level of PI3K and Akt using ELISA and Western blotting. RESULTS: A total of 318 common targets of drugs and diseases were identified, and the core targets were Src, HSP90AA1 and PIK3CA, involving cancer, PI3K/Akt, MAPK and other signaling pathways as shown by KEGG analysis. Molecular docking showed that both the main active constituents of Balanophora involucrata could spontaneously bind to the core targets. In the inflammatory cell model, treatment with Balanophora involucrata extract significantly inhibited the production of IL-1ß at the concentrations of 100 and 200 µg/mL, reduced IL-6 and TNF-α expressions at the concentrations of 50, 100, and 200 µg/mL, and lowered phosphorylation levels of PI3K and Akt proteins at the concentrations of 25, 50, 100, and 200 µg/mL (all P < 0.05). CONCLUSIONS: The anti-inflammatory mechanism of Balanophora involucrata involves multiple targets and multiple pathways, and its effect is mediated possibly by reducing IL-1ß, IL-6 and TNF-α production and inhibiting phosphorylation levels of PI3K and Akt proteins to suppress the activation of the PI3K/Akt signaling pathway.

[Analysis of prognosis and associated factors in multiple recurrent epithelial ovarian cancer with three times or more cytoreductive surgeries].

Objective: To explore the prognosis of epithelial ovarian cancer patients with multiple recurrences (≥2 times) who underwent three times or more cytoreductive surgeries, and to analyze the factors associated with prognosis. Methods: The clinicopathological data and follow-up data of 23 patients with ovarian cancer admitted to the Obstetrics and Gynecology Hospital of Fudan University from January 1, 2015 to January 30, 2022 with three times or more cytoreductive surgeries were collected. The degree of surgical resection, site of recurrence and metastasis, postoperative complications, and prognosis were retrospectively analyzed. The univariate Cox proportional hazards model was performed to identify the variables associated with survival. Results: (1) The median age of 23 patients with multiple recurrent ovarian cancer was 48 years old (44-55 years). Among them, 18 cases underwent tertiary cytoreductive surgery (TCS), 2 cases underwent quaternary cytoreductive surgery, 2 cases underwent quinary cytoreductive surgery, and 1 case underwent senary cytoreductive surgery. Among the 23 patients with multiple recurrent ovarian cancer, 21 cases (91%, 21/23) had serous carcinoma, 16 cases (70%, 16/23) had advanced stage (stage Ⅲ-Ⅳ), and 19 cases (83%, 19/23) had high differentiation. (2) Based on the premise that satisfactory cytoreduction was achieved by primary debulking surgery (PDS) and no visible residual disease (R0) was achieved by secondary cytoreductive surgery (SCS), the maximum diameter of the recurrent tumors was up to 10.0 cm and 62% (20/32) of patients with multiple metastatic sites. The R0 rate for three times or more cytoreductive surgeries (32 times in total) reached 88% (28/32), with a postoperative complication rate of 47% (15/32), and only 3% (1/32) for grade Ⅲ or above. During a median follow-up time of 31.1 months (20.6-43.9 months) after TCS, 20 patients (87%, 20/23) recurred after TCS, and 8 patients (35%, 8/23) eventually died of ovarian cancer. Among them, the three-year postoperative survival rate of 22 patients with R0 was 57.6%, and the patient with residual lesions ≥1 cm died at 9.2 months after TCS. (3) In univariate analysis, ages, the time interval between PDS and SCS >32 months, the interval between SCS and TCS >16 months, and no metastatic peritoneal carcinoma were associated with longer progression free survival after TCS (all P<0.05); while treatment-free interval (TFI) >10 months after SCS, the interval between SCS and TCS >16 months, no ascites and platinum-sensitive status were associated with disease-specific survival after TCS (all P<0.05). Conclusions: It is feasible to perform three times or more cytoreductive surgeries in patients with multiple recurrent ovarian cancer who are expected to achieve R0 and have manageable complications. However, the pros and cons of surgery need to be carefully evaluated for the patients whose ascites are massive and whose previous cytoreduction does not achieve R0. A prolonged TFI and previously longer surgical interval might get potential survival benefits.