Unusual Cause of Acute Stroke in a Young Woman with Patent Foramen Ovale - Duplicated Inferior Vena Cava and May-Thurner Syndrome.

The etiology of acute ischemic stroke (AIS) may often remain uncertain despite diligent work-up, especially in young people. Although patent foramen ovale (PFO) is a frequent association during such work-up, the actual source of thromboembolism, like deep vein thrombosis (DVT), may not be found. Such associative pathology makes it challenging to prescribe anticoagulation for secondary stroke prevention. We describe a young woman with a known history of PFO who presented with AIS and underwent endovascular reperfusion therapy. Post-thrombectomy, she developed hypoxic respiratory failure due to pulmonary embolism. Initiation of therapeutic anticoagulation was complicated by a retroperitoneal bleed necessitating imaging studies for etiological work-up. Computed tomographic angiography and venogram showed no active contrast extravasation but demonstrated duplication of the inferior vena cava with DVT in the right iliofemoral vein (RIFV). The proximity of the right common iliac artery compressing RIFV against the pelvic inlet is described as May-Thurner syndrome (MTS). Afterward, the patient was successfully treated with anticoagulation and PFO closure. MTS is a rare and underdiagnosed cause of iliofemoral DVT. In patients with known PFO, MTS is a possible cause that needs consideration. Hence, appropriate diagnostic tests are necessary to initiate appropriate management and to prevent AIS recurrence.

Atom-photon dressed states in a waveguide-QED system with multiple giant atoms.

We study the properties of bound states in waveguide-QED systems consisting of multiple giant atoms coupled to a coupled-resonator waveguide. Based on the general analytical expressions for these states and the corresponding energy spectra, we analyze in detail the threshold conditions for the appearance of bound states and the photon-mediated interactions between dressed atoms for different configurations. In addition, when multiple giant atoms are coupled to the waveguide, different types of interacting atomic chain can be obtained by manipulating the coupling configurations. Accordingly, the energy spectra of the bound states form metaband structures in the photonic band gaps. This makes the system a useful platform for quantum simulation and quantum information processing.

[Wolfram-like syndrome: a case report].

Different from classical autosomal recessive Wolfram syndrome, Wolfram-like syndrome is an autosomal dominant disorder caused by a heterozygous mutation in the WFS1 gene. In this case, a 7-year-old male child presented to the eye clinic due to vision loss that could not be corrected, discovered during a routine examination. The child had experienced hearing impairment since early childhood, leading to cochlear implantation. Ophthalmic examination revealed optic disc atrophy in both eyes. Optical coherence tomography imaging demonstrated a distinctive thickening of the outer plexiform layer with abnormal layering, characteristic of a single mutation in the WFS1 gene. Subsequent genetic testing identified a de novo heterozygous missense mutation c.2051C>T (p.A684V) in the WFS1 gene, which ultimately led to the diagnosis of Wolfram-like syndrome.

Three-dimensional analysis of mandibular morphology asymmetry and temporomandibular joint position in patients with unilateral Brodie bite.

OBJECTIVE: Previous studies have shown unilateral posterior crossbite is associated with mandibular asymmetry in morphology and position. However, it remains unclear whether unilateral Brodie bite plays a similar role in mandibular development. Therefore, this study aims to investigate the morphological and positional symmetry of mandibles in patients with unilateral Brodie bite by three-dimensional anaylsis. METHODS: Fourteen patients with unilateral Brodie bite (mean age 18.43 ± 4.24 years) and fourteen sex- and age-matched patients with normal occlusion (mean age 18.07 ± 5.48 years) underwent cone-beam computed tomography (CBCT) scans. 3D surface mesh models of their mandibles were established using Mimics Research 19.0. The surface matching percentage was compared between the original and mirrored mandible by Geomagic Control X software. Furthermore, the dimension and position of the temporomandibular joint (TMJ) were determined for both groups using InVivoDental 5.0. RESULTS: For surface-to-surface deviation analysis, the percentage of mismatch in patients with unilateral Brodie bite was significantly higher than the control group at ±0.50 mm, ±0.75 mm, and ±1.00 mm tolerance (P < .001). In patients with unilateral Brodie syndrome, the condyles on the scissors-bite side showed a significantly more anterior position (P = .03), greater medial inclination (P < .01), and larger posterior TMJ space (P = .01) than the non-scissors-bite side. CONCLUSION: Patients with unilateral Brodie bite exhibit a more asymmetrical mandibular morphology, with a greater anterior condylar position and posterior joint space on the scissors-bite side, indicating that early diagnosis and treatment may be necessary for patients with unilateral Brodie bite.

[Association between remnant cholesterol levels and incident diabetic retinopathy in middle-aged and older patients with diabetes].

Objective: To investigate the association between remnant cholesterol (RC) and the risk of diabetic retinopathy (DR) in middle-aged and older individuals with diabetes. Methods: Based on the Shanghai Nicheng Cohort Study database, the data of 1 255 individuals with diabetes aged 55-70 years at baseline (2013-2014) with complete fundus photographs and serum cholesterol data in Nicheng, Shanghai, were analyzed. Multinomial logistic regression models were used to evaluate risk ratios (RRs) and their 95% confidence intervals (CIs) between baseline RC level and incident DR. Results: The median age of the subjects was 61.9 years, and 60.4% were women. After a 4.6-year follow-up, 79 (6.3%) patients developed DR, including 50 (4.0%) mild non-proliferative DR and 29 (2.3%) referable DR (RDR). Multivariable logistic regression showed that each mmol/L increase of RC was associated with a 40% higher risk of RDR (RR=1.40, 95%CI 1.03-1.90). Compared with the lowest tertile of RC (<0.63 mmol/L), the risk of RDR in the highest tertile (≥0.85 mmol/L) increased by 4.59 times (RR=5.59, 95%CI 1.51-20.73). Conclusion: The RC level may help identify individuals at high risk of incident RDR in middle-aged and older Chinese adults with diabetes.

[Chinese expert guidance on overall application of lenvatinib in hepatocellular carcinoma].

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4, 2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

[Efficacy and safety of ultra rapid lispro in the treatment of type 2 diabetes mellitus: a randomized controlled clinical trial].

Objective: To evaluate and compare the efficacy and safety of ultra-rapid lispro insulin (URLi) and humalog lispro (HL) in the treatment of type 2 diabetes mellitus. Methods: This was an international multicenter, double-blind, randomized controlled study. From May 2019 to January 2021, a total of 481 patients with type 2 diabetes mellitus, who had been using insulin for at least 90 days and had poor glycemic control, were included. These patients were recruited from 34 research centers in China, including Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital. They were assigned to either the URLi group (319 patients) or the HL group (162 patients) using stratified blocked randomization. The primary endpoint was the change in hemoglobin A1c (HbA1c) relative to baseline after 26 weeks of treatment. Secondary endpoints included the proportion of patients who achieved HbA1c<7.0% and ≤6.5% after 26 weeks of treatment, 1-h postprandial glucose (1hPG) or 2-h postprandial glucose (2hPG) excursions during a mixed meal tolerance test at week 26, as well as safety parameters. Continuous variables were compared using mixed model repeated measures or analysis of covariance, and categorical variables were compared using logistic regression or Fisher's exact test. Results: Data based on the Chinese subgroup showed that there were no statistically significant differences between the URLi and HL groups in terms of male percentage [56.1% (179/319) vs. 56.2% (91/162); P=0.990], age [(59.5±8.4) vs. (59.6±9.3) years; P=0.839] and other baseline characteristics. Regarding the change in HbA1c relative to baseline, the URLi group was non-inferior to the HL group (-0.59%±0.05% vs. -0.66%±0.06%; P=0.312). There were no statistically significant differences between the URLi and HL groups in proportion of patients who achieved HbA1c<7.0% [47.3% (138/292) vs. 45.2% (70/155); P=0.907] and≤6.5% [27.7% (81/292) vs. 27.7% (43/155); P=0.816]. The excursions in 1hPG [(6.20±0.21) vs. (6.90±0.25) mmol/L; P=0.001] and 2hPG [(8.10±0.27) vs. (9.30±0.31) mmol/L; P<0.001] were lower in the URLi group than the HL group, with statistically significant differences. In terms of safety, there were no statistically significant differences in the percentage of subjects who reported treatment-emergent adverse events between the URLi and HL groups [49.8% (159/319) vs. 50.0% (81/162); P=1.000]. The event rate of nocturnal hypoglycemia was lower in the URLi group than the HL group, with statistically significant differences [(0.53±0.10) vs. (0.89±0.16) events per patient-year; P=0.040]. Conclusions: With good glycemic control, URLi showed non-inferiority for HbA1c improvement versus HL and was superior to HL for postprandial glucose excursion control. Meanwhile the rate and incidence of nocturnal hypoglycemia were lower in the URLi group than the HL group.

[Single-cell RNA sequencing deciphers transcriptional profiles of hepatocytes in mouse with hepatic alveolar echinococcosis].

OBJECTIVE: To investigate the cell composition and the transcriptional characteristics in microenvironments of hepatic tissues in mice at late stage of Echinococcus multilocularis infection at a single-cell level. METHODS: Peri-lesion and paired distal hepatic specimens were collected from two BALB/c mice (6 to 8 weeks old) infected with E. multilocularis for single-cell RNA sequencing. The Seurat package in the R software was employed for quality control of data, multi-sample integration and correction of batch effects, and uniform manifold approximation and projection (UMAP) algorithm was used for cell clustering. Cell types were annotated using classical marker genes. Differentially expressed genes were screened in each cell type through differential gene expression analysis, and the biological roles of cells were predicted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. RESULTS: A total of 43 710 cells from peri-lesion and distal hepatic tissues of E. multilocularis-infected mice were analyzed, and were classified into 11 cell types, including neutrophils, T cells, macrophages, granulocyte-monocyte progenitor cells, B cells, plasma cells, basophils, hepatic stellate cells, endothelial cells, hepatocytes, and platelets. T cells were the largest population of immune cells in the microenvironment of hepatic tissues, including five CD4+ T cell subsets, two CD8+ T cell subsets and phosphoantigen-reactive γδT cells. The proportions of CD4+ helper T cells and cytotoxic CD4+ T cells decreased and the proportion of T helper 2 (Th2) cells increased in peri-lesion tissues relative to distal hepatic tissues. In addition, the differentially expressed genes in Th2 cells were associated with negative regulation of the immune system, and the highly expressed genes in cytotoxic CD4+ T cells correlated with activation of the immune system. CONCLUSIONS: Single-cell RNA sequencing deciphers the cell composition and distribution in microenvironments of hepatic tissues from mice infected with E. multilocularis, and the increased proportion of Th2 cells in peri-lesion hepatic tissues may be associated with formation of immunosuppressive microenvironments.

Efficacy and safety of methylene blue injection for intractable idiopathic pruritus ani: a single-arm metaanalysis and systematic review.

PURPOSE: To evaluate how effective methylene blue injection was at treating intractable idiopathic pruritus ani. METHODS: A comprehensive literature search of the PubMed, Embase, Cochrane library, and Web of Science databases was conducted. All clinical studies (prospective and retrospective) that evaluated the efficacy of methylene blue in treating intractable idiopathic pruritus ani were included. Studies that reported the resolution rate, after a single injection and after a second injection, the recurrence rate, symptom scores, and transient complications of methylene blue injections in treating intractable idiopathic pruritus ani were included. RESULTS: The seven selected studies included 225 patients with idiopathic pruritus ani. The resolution rates after a single injection and after a second injection was 0.761 (0.649-0.873, P < 0.01, I2 = 69.06%) and 0.854 (0.752-0.955, P < 0.01, I2 = 77.391%), respectively, the remission rates at 1, 3, and 5 years were 0.753 (0.612-0.893, P < 0.001), 0.773 (0.675-0.871, P < 0.001) and 0.240 (0.033-0.447, P < 0.001), respectively, the effect value of the merger was 0.569 (0.367-0.772, P < 0.001, I2 = 79.199%), and the recurrence rates at 1, 2, 3, and < 1 year were 0.202 (0.083-0.322, P < 0.001), 0.533 (0.285-0.781, P < 0.001), 0.437 (-0.044, 0.917, P < 0.001) and 0.067 (0.023-0.111, P < 0.001), respectively. The effect value of the merger was 0.223 (0.126-0.319, P < 0.001, I2 = 75.840). CONCLUSION: Using methylene blue injections to treat intractable idiopathic pruritus ani is relatively efficacious, resulting in a relatively low recurrence rate and no severe complications. However, the available literature was of poor quality. Therefore, higher quality studies are necessary to confirm that methylene blue injection is efficacious for pruritus ani, such as a randomized prospective multicenter studies.

Preliminary effectiveness of an evidence-based mobile application to promote resilience among working adults in Singapore and Hong Kong: Intensive longitudinal study.

Evidence-based mobile health (mHealth) applications on smartphones are a cost-effective way for employees to take proactive steps to improve well-being and performance. However, little is known about what sustains engagement on these applications and whether they could dynamically improve occupational outcomes such as resilience and mood. Using real-world data, this intensive longitudinal study examines (a) which employees would continually engage with a cognitive behavioural therapy-informed mHealth application ('Intellect'); and (b) if daily engagement of 'Intellect' would relate to better occupational outcomes on the following day. A total of 515 working adults in Singapore and Hong Kong (Mage = 32.4, SDage = 8.17) completed daily in-app items on mood and resilience components (i.e. sleep hours, sleep quality, physical activity, and stress levels). Our results revealed that employees with lower baseline resilience (ß = -0.048, odds ratio (OR) = 0.953, p < 0.01), specifically poorer sleep quality (ß = -0.212, OR = 0.809, p = 0.001) and/or higher stress levels (ß = -0.255, OR = 0.775, p = 0.05), were more likely to resume engagement on the application. Among the 150 active users (i.e. ≥3 consecutive days of engagement) (Mage = 32.2, SDage = 8.17), daily engagement predicted higher resilience (ß = 0.122; 95% confidence interval (CI) 0.039-0.206), specifically lower stress levels (ß = 0.018; 95% CI 0.004-0.032), higher physical activity (ß = 0.079; 95% CI 0.032-0.126), and mood levels (ß = 0.020; 95% CI 0.012-0.029) on the following day even after controlling for same-day outcomes. Our preliminary findings suggest that engaging with a mHealth application was associated with higher dynamic resilience and emotional well-being in employees.

[Analysis of prognosis and related factors in oldest-old patients with left-side or right-side colon cancer after hemicolectomy].

Objective: This study aimed to explore the difference of prognosis in oldest-old colon cancer patients between the left-side and right-side hemicolectomy. Methods: A total of 238 oldest-old (≥75 years old) colon cancer patients who received surgical treatment in Gastrointestinal Surgery Department of Beijing Hospital from December 2010 to December 2020 were retrospectively collected. They were divided into right-side hemicolectomy (RCC) group (130 cases) and left-side hemicolectomy (LCC) group (108 cases) by surgical methods. The difference in postoperative short-term complications and long-term prognosis was compared between the two groups, and the related factors of postoperative death was analyzed using multivariate Cox regression model. Results: The age of 238 oldest-old patients with colon cancer ranged from 75 to 93 years old (80.5±3.7). There were 128 males and 110 females. The ages of patients in the LCC group and RCC group were (80.4±3.7) and (80.6±3.7) years old (P=0.699), respectively. There was no significant difference in gender, body mass index (BMI) and co-existing chronic diseases between two groups (P>0.05). The proportion of the duration of surgery exceeding 170 min in the LCC group was significantly higher than that in the RCC group (56.5% vs 43.1%, P=0.039). The incidence of postoperative short-term complications in RCC group was slightly higher than LCC group (P>0.05), and there was no significant difference in overall survival (OS), tumor-specific survival (CSS) and disease-free survival (DFS) between two groups. However, the two groups had different prognostic risk factors, pathological Ⅳ stage (HR=28.970,95%CI:1.768-474.813,P=0.018), intraoperative bleeding (HR=2.297,95%CI:1.351-3.907,P=0.002) and cancer nodules (HR=2.044,95%CI:1.047-3.989,P=0.036) were independent prognostic risk factors in LCC group. Underweight (HR=0.428,95%CI:0.192-0.955,P=0.038), overweight(HR=0.316,95%CI:0.125-0.800,P=0.015),obesity (HR=0.211,95%CI:0.067-0.658,P=0.007), lymph node metastasis (HR=2.682,95%CI:1.497-4.807,P=0.001), tumor nodule (HR=2.507,95%CI:1.301-4.831,P=0.027) and postoperative length of stay of 9 days (HR=1.829,95%CI:1.070-3.128,P=0.006) were independent risk factors for poor prognosis in RCC group. Conclusions: The duration of surgery of oldest-old colon cancer patients in the LCC group was longer than that in the RCC group. However, there was no significant difference in the incidence of postoperative complications between the two groups. High pathological stage, more intraoperative bleeding and cancer nodules were independent prognostic risk factors in the LCC group. Abnormal BMI, lymph node metastasis, cancer nodules and postoperative length of stay were independent risk factors for poor prognosis in the RCC group.

Single-photon switches, beam splitters, and circulators based on the photonic Aharonov-Bohm effect.

Single-photon devices such as switches, beam splitters, and circulators are fundamental components to construct photonic integrated quantum networks. In this paper, two V-type three-level atoms coupled to a waveguide are proposed to simultaneously realize these functions as a multifunctional and reconfigurable single-photon device. When both the two atoms are driven by the external coherent fields, the difference in the phases of the coherent driving induces the photonic Aharonov-Bohm effect. Based on the photonic Aharonov-Bohm effect and setting the two-atom distance to match the constructive or destructive interference conditions among photons travelling along different paths, a single-photon switch is achieved since the incident single photon can be controlled from complete transmission to complete reflection by adjusting the amplitudes and phases of the driving fields. When properly changing the amplitudes and phases of the driving fields, the incident photons are split equally into multiple components as a beam splitter operated with different frequencies. Meanwhile, the single-photon circulator with reconfigurable circulation directions can also be obtained.

Global transcriptome and gene co-expression network analyses reveal regulatory and non-additive effects of drought and heat stress in grapevine.

Despite frequent co-occurrence of drought and heat stress, the molecular mechanisms governing plant responses to these stresses in combination have not often been studied. This is particularly evident in non-model, perennial plants. We conducted large scale physiological and transcriptome analyses to identify genes and pathways associated with grapevine response to drought and/or heat stress during stress progression and recovery. We identified gene clusters with expression correlated to leaf temperature and water stress and five hub genes for the combined stress co-expression network. Several differentially expressed genes were common to the individual and combined stresses, but the majority were unique to the individual or combined stress treatments. These included heat-shock proteins, mitogen-activated kinases, sugar metabolizing enzymes, and transcription factors, while phenylpropanoid biosynthesis and histone modifying genes were unique to the combined stress treatment. Following physiological recovery, differentially expressed genes were found only in plants under heat stress, both alone and combined with drought. Taken collectively, our results suggest that the effect of the combined stress on physiology and gene expression is more severe than that of individual stresses, but not simply additive, and that epigenetic chromatin modifications may play an important role in grapevine responses to combined drought and heat stress.

Brown goat yogurt: Metabolomics, peptidomics, and sensory changes during production.

Brown goat milk products have gained popularity for their unique taste and flavor. The emergence of chain-reversal phenomenon makes the design and development of goat milk products gradually tend to a consumer-oriented model. However, the precise mechanism of how browning and fermentation process causes characteristics is not clear. In an effort to understand how the treatments potentially lead to certain metabolite profile changes in goat milk, comprehensive, quantitative metabolomics and peptidomics analysis of goat milk samples after browning and fermentation were undertaken. An intelligent hybrid z-score standardization-principal components algorithm-multimodal denoizing autoencoder was used for feature fusion and hidden layer fusion in high-dimensional variable space. The fermentation process significantly improved the flavor of brown goat yogurt through the tricarboxylic acid-urea-glycolysis composite pathway. Bitter peptides HPFLEWAR, PPGLPDKY, and PPPPPKK have strong interactions with both putative dipeptidyl peptidase IV and angiotensin-converting enzyme, proving that brown goat yogurt can be considered as effective provider of potential putative dipeptidyl peptidase IV and angiotensin-converting enzyme inhibitors. The level of health-promoting bioactive components and sensory contributed to consumer selection. The proposed multimodal data integrative analysis platform was applicable to explain the effect of the dynamic changes of metabolites and peptides on consumer preferences.

[Clinical and genetic studies of a family with hereditary angioedema].

Objective: To diagnose a large family of patients with hereditary angioedema, and to study its inheritance pattern and gene locus. Methods: A retrospective analysis was carried out from August 2021 to February 2022 in a proband (female, 48 years old) and 12 family members who underwent medical history collection and laboratory examinations in the Department of Otorhinolaryngology and Head and Neck Surgery, the Second Hospital of Shanxi Medical University. The clinical data of members and non-affected members [including 7 males and 5 females, aged 12-78 (median 24) years old], were drawn a family map while confirming the diagnosis. Whole exome sequencing technology was used to detect the genetic sequence of the proband and to verify its family members to map the genetic pedigree of the mutation. Results: The inheritance pattern of the family was autosomal dominant, and 8 members of the family were diagnosed with hereditary angioedema by laboratory examination, including 7 cases of type I and 1 case of type Ⅱ. Whole exome sequencing analysis was performed on 2 patients with 2 phenotypes, and it was found that they both carried the same pathogenic mutation locus, which was c.890-2A>G. The family members were verified by next-generation sequencing, and it was found that all members of the family who had a history of edema contained this mutation site, while the younger brother of the proband who had no history of edema did not have this mutation. Conclusion: Both type Ⅰ and type Ⅱ phenotypes are present in this hereditary angioedema family, and the mutation of SERPING1 gene c.890-2A>G causes the onset of each patient in this family.