A modified Nishida procedure for management of myopic strabismus fixus.

PURPOSE: To evaluate the outcomes of a novel modification of the Nishida procedure with medial rectus recession (Nishida-MRc) for myopic strabismus fixus (MSF) and to compare this modified procedure with the half Jensen's union with medial rectus recession (U-MRc). METHODS: The medical records of MSF patients who underwent strabismus surgery at a single institution between January 2017 and June 2022 were retrospectively reviewed. The main outcome measures assessed were postoperative improvements in ocular alignment and motility. Surgical success was defined as horizontal and vertical deviations ≤15Δ. RESULTS: A total of 45 patients were included, of whom 39 had no previous strabismus surgery. All but 3 had follow-up ≥8 months. Nishida-MRc, with or without a traction suture (Ts), had a success rate (9/16 [56%]) higher, though not statistically significantly so, than U-MRc with or without Ts (11/29 [38%]). The Nishida-MRc group tended to have less frequent use of Ts (25% vs 52%; P = 0.076), and 94% of these patients had a deviation within 20Δ, compared with 59% for U-MRc (P = 0.012). In cases with esotropia of ≥123Δ, final residual esotropia in the Nishida-MRc without Ts (12.40Δ ± 8.30Δ) and U-MRc-Ts (19.75Δ ± 18.62Δ) groups was significantly lower (P = 0.019) than in the U-MRc without Ts group (63.40Δ ± 40.83Δ), and the average correction of esotropia was significantly greater (P = 0.014). CONCLUSIONS: In our study cohort, Nishida-MRc produced a greater effect in the treatment of MSF than U-MRc.

Targeting cathepsin S promotes activation of OLF1-BDNF/TrkB axis to enhance cognitive function.

BACKGROUND: Cathepsin S (CTSS) is a cysteine protease that played diverse roles in immunity, tumor metastasis, aging and other pathological alterations. At the cellular level, increased CTSS levels have been associated with the secretion of pro-inflammatory cytokines and disrupted the homeostasis of Ca2+ flux. Once CTSS was suppressed, elevated levels of anti-inflammatory cytokines and changes of Ca2+ influx were observed. These findings have inspired us to explore the potential role of CTSS on cognitive functions. METHODS: We conducted classic Y-maze and Barnes Maze tests to assess the spatial and working memory of Ctss-/- mice, Ctss+/+ mice and Ctss+/+ mice injected with the CTSS inhibitor (RJW-58). Ex vivo analyses including long-term potentiation (LTP), Golgi staining, immunofluorescence staining of sectioned whole brain tissues obtained from experimental animals were conducted. Furthermore, molecular studies were carried out using cultured HT-22 cell line and primary cortical neurons that treated with RJW-58 to comprehensively assess the gene and protein expressions. RESULTS: Our findings reported that targeting cathepsin S (CTSS) yields improvements in cognitive function, enhancing both working and spatial memory in behavior models. Ex vivo studies showed elevated levels of long-term potentiation levels and increased synaptic complexity. Microarray analysis demonstrated that brain-derived neurotrophic factor (BDNF) was upregulated when CTSS was knocked down by using siRNA. Moreover, the pharmacological blockade of the CTSS enzymatic activity promoted BDNF expression in a dose- and time-dependent manner. Notably, the inhibition of CTSS was associated with increased neurogenesis in the murine dentate gyrus. These results suggested a promising role of CTSS modulation in cognitive enhancement and neurogenesis. CONCLUSION: Our findings suggest a critical role of CTSS in the regulation of cognitive function by modulating the Ca2+ influx, leading to enhanced activation of the BDNF/TrkB axis. Our study may provide a novel strategy for improving cognitive function by targeting CTSS.

Binocular Summation With Quantitative Contrast Sensitivity Function: A Novel Parameter to Evaluate Binocular Function in Intermittent Exotropia.

Purpose: Intermittent exotropia (IXT) is the most common form of strabismus. Surgery can potentially improve binocular function in patients with IXT. We aimed to evaluate binocular function using a novel parameter-binocular summation ratio (BSR), measured using quantitative contrast sensitivity function (CSF) in patients with IXT before and after surgery. Methods: Prospective study of 63 patients with IXT and 41 healthy controls were consecutively enrolled and underwent quantitative CSF testing binocularly and monocularly. BSR was calculated by dividing the CSF of the binocular value by the better monocular value. Forty-eight patients with IXT underwent strabismus surgery. BSR, stereoacuity, fusion ability, and strabismus questionnaires were assessed pre-operatively and 2 months postoperatively. Results: Sixty-three patients with IXT (median age = 9 years) compared with 41 healthy controls showed a worse mean BSR based on all CSF metrics at baseline (the area under the log CSF [AULCSF], spatial frequency [SF] cutoff, and contrast sensitivity at 1.0-18.0 cpd SF). All 48 patients with IXT showed successful alignment after surgery, and there were significant improvements in BSR based on the AULCSF, SF cutoff, and contrast sensitivity at 6.0, 12.0, and 18.0 cpd SF, respectively. The distance stereoacuity and fusion ability also improved after surgery, and a better BSR was associated with better stereoacuity and fusion. For strabismus questionnaires, the psychosocial subscale scores improved postoperatively, whereas the functional subscale scores did not change. Conclusions: BSR based on quantitative CSF can characterize binocular function across a range of spatial frequencies and can be used as a supplemental measurement for monitoring binocularity in patients with IXT in clinical settings.

Relationships between bilateral auditory brainstem activity and inter-implant interval in children with cochlear implants.

PURPOSE: To investigate the effect of the interval between bilateral cochlear implantation on the development of bilateral peripheral auditory pathways as revealed by the electrically evoked auditory brainstem response (EABR). METHODS: Fifty-eight children with profound bilateral sensorineural hearing loss were recruited. Among them, 33 children received sequential bilateral cochlear implants (CIs), and 25 children received simultaneous bilateral CIs. The bilateral EABRs evoked by electrical stimulation from the CI electrode were recorded on the day of second-side CI activation. RESULTS: The latencies of wave III (eIII) and wave V (eV) were significantly shorter on the first CI side than on the second CI side in children with sequential bilateral CIs but were similar between the two sides in children with simultaneous bilateral CIs. Furthermore, the latencies were prolonged from apical to basal channels along the cochlea in the two groups. In children with sequential CIs, the inter-implant interval was negatively correlated with the eV latency on the first CI side and was positively correlated with bilateral differences in the eIII and eV latencies. CONCLUSIONS: Unilateral CI use promotes the maturation of ipsilateral auditory conduction function. However, a longer inter-implant interval results in more unbalanced development of bilateral auditory brainstem pathways. Bilateral cochlear implantation with no or a short interval is recommended.

Comparison of the Utility of PI-RADS 2.1, ADC Values, and Combined Use of Both, for the Diagnosis of Transition Zone Prostate Cancers.

OBJECTIVE: To assess the performance of apparent diffusion coefficient (ADC; values or category) alone, Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) scoring alone, and the two in combination, to diagnose transition zone prostate cancers (PCas). METHODS: This retrospective study included 222 patients who underwent multiparametric magnetic resonance imaging of the prostate between May 2020 and December 2022 and who had pathologically confirmed PCa or benign prostatic hyperplasia (BPH). Prostate Imaging Reporting and Data System version 2.1 and ADC (values or category) were used in the assessment of suspicious findings identified in the transition zone. The interobserver agreements for region-of-interest measurements were calculated by intraclass correlation coefficients. Logistic regression analyses were used to determine the performance of PI-RADS v2.1 alone and in combination with ADC (values or category) to diagnose PCa. Receiver operating characteristic curve and DeLong test were used to evaluate the diagnostic performance of the quantitative parameters. RESULTS: A total of 152 patients had BPH, and 70 patients had PCa. For BPH versus PCa, the ADC values of PCa (0.64 × 10 -3 ± 0.16 × 10 -3 mm 2 /s) were significantly lower than BPH (1.06 ± 0.18 × 10 -3 mm 2 /s; P < 0.001). The PI-RADS scores for PCa (5 [interquartile range, 5-5]) were significantly higher than BPH (2 [interquartile range, 2-3]; P < 0.001). For all patients who had PI-RADS 1-5, the combined use of ADC (values or category) together with PI-RADS v2.1 did not perform significantly better than the use of PI-RADS v2.1 alone. The receiver operating characteristic of ADC category in combination with PI-RADS v2.1 score, 0.756 (95% confidence interval, 0.646-0.846), was significantly higher than that for PI-RADS 2.1 alone, 0.631 (95% confidence interval, 0.514-0.738), in PI-RADS 3-4 lesions ( P = 0.047). CONCLUSION: The ADC category can help to improve the diagnostic performance of PI-RADS v2.1 category 3-4 lesions in diagnosing PCa.

Prenatal diagnosis of autosomal recessive Noonan syndrome associated with biallelic LZTR1 variants presented with thick nuchal translucency and cardiac abnormalities.

Noonan syndrome (NS) is a common clinical variable disease characterized by a number of features, mainly including congenital heart defects, short stature, and a variable degree of developmental delay. This disorder is transmitted mostly in an autosomal dominant manner and is genetically heterogeneous. We report three prenatal cases of LZTR1-related recessive NS. One case had a recurrent cystic hygroma at 13 weeks gestation and the pregnancy was terminated. Two cases had an increased nuchal translucency at 12 weeks' gestation, but a normal second trimester ultrasound; both presented with hypertrophic cardiomyopathy in the third trimester. The two infants were diagnosed with NS after birth. All of the three cases had invasive genetic investigations during pregnancy, and trio exome sequencing revealed biallelic likely pathogenic or pathogenic LZTR1 variants in the fetuses. All parents were LZTR1 variant carriers. Our report further strengthens the association of LZTR1 with an autosomal recessive form of NS. The affected fetuses are more likely to have cardiac anomalies. Clarification of molecular diagnosis has important implications in these families because they carry a 25% recurrence risk.

Refractive Profile of Surgical Patients with Intermittent Exotropia: A Large-Sample Cross-Sectional Study in Southern China.

PURPOSE: To describe the refractive profile of surgical patients with intermittent exotropia (IXT) residing in southern China. METHODS: Medical records of patients who received strabismus surgery between June 2014 and August 2020 were retrospectively reviewed. Clinical data, including age, sex, refractive errors, preoperative angle of deviation, types of exotropia, accommodative convergence to accommodation ratio (AC/A ratio) and stereopsis, were investigated. RESULTS: A total of 2250 patients were included, and 93.6% of patients were younger than 30 years of age. The mean angle of exodeviation was 37.0 ± 14.7 prism degree (PD) and 37.5 ± 15.8 PD at distance and near, respectively. Mean spherical equivalent refraction (SER) values were -0.7 ± 2.4 D and -0.8 ± 2.5 D in the dominant eye and nondominant eye, respectively. Significant differences in SER were observed between the dominant eye and nondominant eye among children at 6 years old or younger. The percentage of myopia increased from 11.0% in children (≤6 years old) to 77.9% in teenagers (13-18 years of age). Significant positive associations between the magnitude of exodeviation and the magnitude of myopia were observed (p < 0.0001). Patients with convergence insufficiency type IXT (p < 0.0001) or AC/A < 2 (p < 0.05) showed a greater magnitude of myopia. The mild hyperopia group included a larger proportion of subjects showing a certain degree of stereopsis (p < 0.05). CONCLUSIONS: Myopia was present in more than half of our patients (51.2%), which is much higher than the percentage in the general population of southern China. Patients with convergence insufficiency, an AC/A ratio < 2, or a larger angle of deviation tended to have a greater magnitude of myopia.

Perioperative, functional, and oncologic outcomes of minimally-invasive surgery for highly complex renal tumors (RENAL or PADUA score ≥ 10): an evidence-based analysis.

The primary objective of the current study is to undertake a comparative analysis of the effectiveness and safety of minimally-invasive partial nephrectomy (MIPN; including laparoscopic and robotic approaches) and open partial nephrectomy (OPN) for the treatment of highly complex renal tumors (defined as PADUA or RENAL score ≥ 10). A comprehensive search was conducted in four electronic databases (PubMed, Web of Science, Embase, and Cochrane Library) to identify relevant studies published in the English language up to April 2023. The current study employed Review Manager 5.4 and encompassed controlled trials of both MIPN and OPN for the treatment of highly complex renal tumors. This study comprised a total of eight comparative trials involving 1161 patients. MIPN demonstrated a significant reduction in length of hospital stay (weighted mean difference [WMD] - 2.08 days, 95% confidence interval [CI] - 2.48, - 1.68; p < 0.00001), blood loss (WMD - 39.86 mL, 95% CI - 75.32, - 4.39; p = 0.03), transfusion rates (odds ratio [OR] 0.30, 95% CI 0.13, 0.71; p = 0.006), and overall complications (OR 0.46, 95% CI 0.31, 0.70; p = 0.0003). However, there were no significant differences between MIPN and OPN in terms of operative time, warm ischemia time, conversion to radical nephrectomy rates, renal functional and oncologic outcomes. This study reveals that MIPN presents several benefits in comparison to OPN, including decreased length of hospital stay, blood loss, transfusion rates, and complications, while still offering renal functional and oncological outcomes that are comparable to those of OPN in patients with highly complex renal tumors.

APEX1 predicts poor prognosis of gallbladder cancer and affects biological properties of CD133+ GBC-SD cells via upregulating Jagged1.

Although APEX1 is associated with the tumorigenesis and progression of some human cancer types, the function of APEX1 in gallbladder cancer (GBC) is unclear. In this study, we found that APEX1 expression is up-regulated in GBC tissues, and APEX1 positive expression is related to aggressive clinicopathological features and poor prognosis of GBC. APEX1 was an independent risk factor of GBC prognosis, and presented some pathological diagnostic significance in GBC. Furthermore, APEX1 was overexpressed in CD133+ GBC-SD cells in comparison with GBC-SD cells. APEX1 knockdown increased the sensitivity of CD133+ GBC-SD cells to 5-Fluorouracil via facilitating cell necrosis and apoptosis. APEX1 knockdown in CD133+ GBC-SD cells dramatically inhibited cell proliferation, migration, and invasion, and promoted cell apoptosis in vitro. APEX1 knockdown in CD133+ GBC-SD cells accelerated tumor growth in the xenograft models. Mechanistically, APEX1 affected these malignant properties via upregulating Jagged1 in CD133+ GBC-SD cells. Thus, APEX1 is a promising prognostic biomarker, and a potential therapeutic target for GBC.

The effects of music therapy on peripherally inserted central catheter in hospitalized children with leukemia.

To explore the effect of music therapy on children with leukemia who have peripherally inserted central catheters (PICC).In this study, we divided 107 patients undergoing PICC into music group (47 cases) and control group (60 cases). The music group received music therapy during PICC, while the control group was given no complementary treatment. The total length of catheterization, the use of sedatives and the changes of pain level and emotion level before and after PICC placement were compared between two groups.Compared with the control group, the total PICC placement time of the music group was significantly shorter (35(30-40) vs. 60(60-60); Z = -8.307; p < 0.001), and the use of sedative medications was also significantly reduced (4.35% (n = 2) vs. 91.84% (n = 45); p < 0.001). Moreover, the pain of catheterization was significantly alleviated. The median difference of pain scores of the music group was significantly less (2(1-3) vs. 5(5-5); p < 0.001). The mood of patients was also improved. The median difference of emotional scores of the music group was significantly more (5(4.75-6) vs. 3(3-3); p < 0.001) than the control group.Music therapy is effective to use in PICC. It can shorten the treatment time, reduce the use of sedative medications, and improve the children's emotion and pain response significantly, which is worth clinical application.

Larger Than Larger: Huge Amounts of Recession-Resection Surgery for Third Nerve Palsy.

PURPOSE: To describe the characteristics and management outcomes of strabismus surgery in patients with third cranial nerve palsy and identify factors associated with long-term outcomes. METHODS: A 10-year retrospective study of patients with third cranial nerve palsy who underwent strabismus surgery was performed at Zhongshan Ophthalmic Center, Sun Yat-sen University, China, between August 2010 and January 2021. Clinical characteristics and factors associated with long-term outcomes were evaluated. Success of surgery was defined as esotropia of 15 prism diopters (PD) or less at postoperative day 1 (POD1) or any deviation of 10 PD or less at postoperative month 2 (POM2) or later. RESULTS: A total of 91 patients were included, with a mean age of 24.02 ± 15.38 years (range: 2 to 64 years). Forty-one patients (45.1%) were diagnosed as having complete palsy. Congenital palsy accounted for 40.7% (n = 37). Mean follow-up time was 2.50 ± 1.78 years (range: 8 months to 8 years). One-step surgery was performed in 78.0% of cases (n = 71), a staging procedure in 7.7% (n = 7), and reoperations in 14.3% (n = 13). Most patients had supra-maximal recession and resection of the horizontal rectus muscle with additional techniques, including horizontal rectus transposition, superior oblique transposition, traction sutures, and fixation of the globe. The mean surgical dosage performed on the horizontal rectus muscle was 18.52 ± 5.69 mm (range: 8 to 35 mm). Success rates at postoperative month 8 (POM8) were 69.0% (49 of 71) in the one-step surgery group, 57.1% (4 of 7) in the staging surgery group, and 46.2% (6 of 13) in the reoperation group. Preoperative horizontal deviation (odds ratio [OR]: 1.07, 95% CI: 1.02 to 1.13, P = .011), horizontal deviation at POD1 (OR: 0.86, 95% CI: 0.76 to 0.97, P = .016), and horizontal deviation at POM2 (OR: 1.53, 95% CI: 1.18 to 1.98, P = .001) were associated with the outcomes at POM8. Patients with partial palsy had a higher success rate than those with complete palsy (76.0% vs 51.2%, P = .014). CONCLUSIONS: Supra-maximal recession and resection with additional techniques yields satisfying surgical results in patients with third nerve palsy when a larger surgical dose is performed for an initial overcorrection for 15 to 25 PD at POD1. The cases with complete palsy showing a larger deviation were prone to failure. [J Pediatr Ophthalmol Strabismus. 2023;60(3):184-194.].

Comparison of tropomyosin released peptide and epitope mapping after in vitro digestion from fish (Larimichthys crocea), shrimp (Litopenaeus vannamei) and clam (Ruditapes philippinarum) through SWATH-MS based proteomics.

Tropomyosin (TM) is a major shellfish allergen and a minor fish allergen. Different digestion profiles affect potential allergen anaphylaxis of protein. In this study, released peptides of fish-TM, shrimp-TM, and clam-TM by in vitro digestion of simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and gastrointestinal (GI) were analyzed using sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS) based proteomics. Results showed that digestion products of shrimp-TM yielded a lot of peptides matched T/B cell epitopes while core regions matched epitopes were distributed along the entire chain. Pepsin or trypsin-based digestion products of shrimp-TM presented many more peptides matched T/B cell epitopes compared with those of fish-TM and clam-TM. Besides, a differentiating peptide of VEKDKALSNAEGEVAAL (72-88) overlapped T/B cell epitopes could be used as a candidate peptide marker to identify tropomyosin allergen. These findings would supply new insight into the different allergenicity of tropomyosin.

A chemometric study on the identification of 5-methylfurfural and 2-acetylfuran as particular volatile compounds of oxidized fish oil based on SHS-GC-IMS.

Fish oil develops particular off-odors, mainly fishy odor, from the oxidation of its characteristic fatty acids, docosahexaenoic (DHA) and eicosapentaenoic (EPA). Anchovy oil (AO) was taken as representative of fish oils. This was compared to three vegetable oils with different fatty acid compositions, i.e. camellia, sunflower and linseed oil, and differential volatile compounds were identified by static-headspace gas-chromatography ion-mobility-spectrometry (SHS-GC-IMS) and orthogonal partial-least-squares discriminant analysis (OPLS-DA) during oxidation at 60 °C. Three groups of differential volatile compounds detected at higher concentrations in the AO were screened out and two compounds, identified as 5-methylfurfural and 2-acetylfuran, were characteristic to the AO and not found in the vegetable oils. They were formed from both EPA and DHA, only present in the AO, and their formation mechanisms were proposed. The contents of 5-methylfurfural and 2-acetylfuran increased linearly with the oxidation time and consequently they could be used as oxidative markers of fish oils.

Concomitant oxidation of fatty acids other than DHA and EPA plays a role in the characteristic off-odor of fish oil.

The aim of the present research was to explore the development of off-odors in fish oil from the perspective of fatty acid oxidation. It was found that the off-odors elicited by the two major ω-3 PUFAs in fish oil, i.e. DHA and EPA, were different from those by fish oil. Results showed that simultaneous oxidation of fatty acids other than DHA and EPA can be involved. The off-odors of fish oil was successfully simulated by combining oxidized samples of DHA, EPA and sunflower oil. Therefore, oxidation of oleic and linoleic acids also contributed to the off-odors in fish oil. A novel analytical approach that consisted in the combination of gas chromatography-ion mobility spectrometry (GC-IMS) and orthogonal partial least squares discriminant analysis (OPLS-DA) was applied to identify differences in the volatile components between the recombinant oil and the fish oil.

Ultramultiplex NaLnF4 Nanosatellites Combined with ICP-MS for Exosomal Multi-miRNA Analysis and Cancer Classification.

Quantification of exosomal multi-miRNA can reveal the initiation, progression, and metastasis of tumors, which is conducive to the noninvasive early diagnosis of cancer. However, low-sensitivity and single-plex detection characteristics of traditional methods seriously hinder the accuracy and specificity of exosomal miRNAs in cancer diagnosis. Herein, we design an ultramultiplexing strategy that enables simultaneous and sensitive detection of multiple exosomal miRNAs by nanosatellites (magnetic beads (MBs) @ NaLnF4) and catalytic hairpin assembly (CHA) amplification in combination with inductively coupled plasma-mass spectrometry (ICP-MS) to diagnose cancer accurately. The competitive binding of target exosomal miRNAs with the recognition sequences on nanosatellites triggers the drop of NaLnF4 from MBs, followed by a CHA reaction that releases more NaLnF4 labels for ICP-MS detection. This method is used to detect ten types of miRNAs simultaneously with a detection limit of 0.01 fM, which is one order of magnitude lower than the quantitative reverse transcription polymerase chain reaction (qRT-PCR) method. Linear discriminant analysis as a machine learning algorithm is subsequently applied to analyze the signals of exosomal multi-miRNA, and the discrimination accuracy of ten cell exosomes reaches 98.6%. In a clinical cohort of 42 patients, including five cancer types and healthy controls, exosomal multi-miRNA analysis achieves accurate cancer diagnosis and classification with 100% accuracy. Our results show that the combination of nanosatellites, CHA, and ICP-MS provides a universal biosensing platform for simultaneous and ultrasensitive detection of multiple targets.

Simplification of the complex: Successful management of large-angle exodeviation after endoscopic sinus surgery.

PURPOSE: To report the clinical characteristics and successful management of large-angle exodeviation due to medial rectus muscle (MR) transection incurred during endoscopic sinus surgery (ESS). METHODS: The medical records of 5 consecutive inpatients with MR complete transection following ESS resulting in large-angle paralytic exodeviation between November 2014 and June 2021 were reviewed. The type of muscle injury, clinical characteristics, surgical procedure and dosage, and long-term outcomes were evaluated. RESULTS: All 5 patients manifested exodeviations of 72 PD to >133 PD with no adduction capacity (graded -4); all of them had proven orbital trauma and complete MR transection with a ≥20 mm distal (globe attached) stump based on CT scans and/or MRI imaging. They underwent a supra-maximal recession (10-12 mm) of the lateral rectus and resection (10-15 mm) of the medial rectus on the affected eye. At least 1 year (1 to 5 years) following the corrective surgery, the patients still maintained orthophoria or had a small angle of exotropia (≤ 8 PD) in primary gaze with successful fusion, and 3 of them (Case 3, 4, and 5) exhibited a certain degree of stereopsis. In addition, appreciable adduction occurred (graded -1 to -3). CONCLUSIONS: A supra-maximal recession/resection shows favorable outcomes in patients with proven complete transection MR with a ≥20 mm distal (globe attached) stump. It can help to achieve good ocular alignment and even yield improvements in adduction over time.

miR-99a-5p: A Potential New Therapy for Atherosclerosis by Targeting mTOR and Then Inhibiting NLRP3 Inflammasome Activation and Promoting Macrophage Autophagy.

Objective: MicroRNAs have been revealed to be involved in the development of atherosclerosis. The present study is aimed at exploring the potential of miR-99a-5p as a therapy for atherosclerosis. We suspected that miR-99a-5p might inhibit NLRP3 inflammasome activation and promote macrophage autophagy via constraining mTOR, therefore, alleviating atherosclerosis. Methods: The cell viability in ox-LDL-induced THP-1 macrophages was assessed by CCK-8 assay. Bioinformatic analysis was used to predict the target genes of miR-99a-5p. The binding between miR-99a-5p and mTOR was confirmed by luciferase reporter assay. In vivo, a high-fat-diet-induced atherosclerosis model was established in apolipoprotein E knockout mice. Hematoxylin-eosin, oil red O, and Sirius red staining were performed for the determination of atherosclerotic lesions. MTOR and associated protein levels were detected by Western blot analysis. Results: miR-99a-5p inhibited NLRP3 inflammasome activation and promoted macrophage autophagy by targeting mTOR. Enforced miR-99a-5p significantly reduced the levels of inflammasome complex and inflammatory cytokines. Furthermore, miR-99a-5p overexpression inhibited the expression of mTOR, whereas mTOR overexpression reversed the trend of the above behaviors. In vivo, the specific overexpression of miR-99a-5p significantly reduced atherosclerotic lesions, accompanied by a significant downregulation of autophagy marker CD68 protein expression. Conclusion: We demonstrated for the first time that miR-99a-5p may be considered a therapy for atherosclerosis. The present study has revealed that miR-99a-5p might inhibit NLRP3 inflammasome activation and promote macrophage autophagy by targeting mTOR, therefore, alleviating atherosclerosis.

Impact of prior thoracoscopic experience on the learning curve of robotic McKeown esophagectomy: a multidimensional analysis.

PURPOSE: Left upper mediastinal lymph node dissection (UMLND)-a technically demanding step of McKeown esophagectomy-is frequently complicated by recurrent laryngeal nerve (RLN) palsy. Under the hypothesis that robotic esophagectomy (RE) could increase the safety and feasibility of UMLND, we retrospectively investigated the degree to which a pre-existing experience in video-assisted thoracoscopic esophagectomy (VATE) may affect the learning curves of this critical part of RE. METHODS: Surgeon A had previously performed > 150 VATE procedures before transitioning to RE. While surgeon B had previously assisted to 50 RE, his pre-existing VATE experience consisted of less than five procedures. A total of 103 and 76 McKeown RE procedures were performed by surgeons A and B, respectively. The learning curve of left UMLND for each surgeon was examined using the cumulative sum method. RESULTS: The inflection point of RLN palsy for surgeon A occurred at patient 31. While the nerve palsy rate decreased from 32.3 to 4.2% (p < 0.001), the number of nodes harvested during left UMLND did not appreciably change. Surgeon B showed a bimodal learning curve for RLN palsy with primary and secondary inflection points at patients 15 and 49, respectively. The RLN palsy rate initially decreased from 66.7% (patients 1-15) to 14.7% (patients 16-49), followed by an additional decline to 3.7% (patients 50-76). However, the number of nodes harvested during left UMLND showed a downtrend which was paralleled by decreasing rates of RLN palsy. These results indicate that surgeon B has not yet reached an ideal balance between an extensive UMLND and nerve protection. CONCLUSION: The pre-existing VATE experience seems to affect the learning curves of left UMLND during RE.

Differential value of diffusion kurtosis imaging and intravoxel incoherent motion in benign and malignant solitary pulmonary lesions.

Objective: To investigate the diagnostic value of diffusion kurtosis imaging (DKI) and intravoxel incoherent motion (IVIM) whole-lesion histogram parameters in differentiating benign and malignant solitary pulmonary lesions (SPLs). Materials and Methods: Patients with SPLs detected by chest CT examination and with further routine MRI, DKI and IVIM-DWI functional sequence scanning data were recruited. According to the pathological results, SPLs were divided into a benign group and a malignant group. Independent samples t tests (normal distribution) or Mann‒Whitney U tests (nonnormal distribution) were used to compare the differences in DKI (Dk, K), IVIM (D, D*, f) and ADC whole-lesion histogram parameters between the benign and malignant SPL groups. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency of the histogram parameters and determine the optimal threshold. The area under the curve (AUC) of each histogram parameter was compared by the DeLong method. Spearman rank correlation was used to analyze the correlation between histogram parameters and malignant SPLs. Results: Most of the histogram parameters for diffusion-related values (Dk, D, ADC) of malignant SPLs were significantly lower than those of benign SPLs, while most of the histogram parameters for the K value of malignant SPLs were significantly higher than those of benign SPLs. DKI (Dk, K), IVIM (D) and ADC were effective in differentiating benign and malignant SPLs and combined with multiple parameters of the whole-lesion histogram for the D value, had the highest diagnostic efficiency, with an AUC of 0.967, a sensitivity of 90.00% and a specificity of 94.03%. Most of the histogram parameters for the Dk, D and ADC values were negatively correlated with malignant SPLs, while most of the histogram parameters for the K value were positively correlated with malignant SPLs. Conclusions: DKI (Dk, K) and IVIM (D) whole-lesion histogram parameters can noninvasively distinguish benign and malignant SPLs, and the diagnostic performance is better than that of DWI. Moreover, they can provide additional information on SPL microstructure, which has important significance for guiding clinical individualized precision diagnosis and treatment and has potential clinical application value.

Radiation dose levels in chest computed tomography scans of coronavirus disease 2019 pneumonia: A survey of 2119 patients in Chongqing, southwest China.

ABSTRACT: To investigate computed tomography (CT) diagnostic reference levels for coronavirus disease 2019 (COVID-19) pneumonia by collecting radiation exposure parameters of the most performed chest CT examinations and emphasize the necessity of low-dose CT in COVID-19 and its significance in radioprotection.The survey collected RIS data from 2119 chest CT examinations for 550 COVID-19 patients performed in 92 hospitals from January 23, 2020 to May 1, 2020. Dose data such as volume computed tomography dose index, dose-length product, and effective dose (ED) were recorded and analyzed. The radiation dose levels in different hospitals have been compared, and average ED and cumulative ED have been studied.The median dose-length product, volume computed tomography dose index, and ED measurements were 325.2 mGy cm with a range of 6.79 to 1098 mGy cm, 9.68 mGy with a range of 0.62 to 33.80 mGy, and 4.55 mSv with a range of 0.11 to 15.37 mSv for COVID-19 CT scanning protocols in Chongqing, China. The distribution of all observed EDs of radiation received by per patient undergoing CT protocols during hospitalization yielded a median cumulative ED of 17.34 mSv (range, 2.05-53.39 mSv) in the detection and management of COVID-19 patients. The average number of CT scan times for each patient was 4.0 ±â€Š2.0, and the average time interval between 2 CT scans was 7.0 ±â€Š5.0 days. The average cumulative ED of chest CT examinations for COVID-19 patients in Chongqing, China greatly exceeded public limit and the annual dose limit of occupational exposure in a short period.For patients with known or suspected COVID-19, a chest CT should be performed on the principle of rapid-scan, low-dose, single-phase protocol instead of routine chest CT protocol to minimize radiation doses and motion artifacts.