Lymph node metrics following neoadjuvant therapy to refine patient selection for adjuvant chemotherapy in resected pancreatic cancer: A multi-institutional analysis.

BACKGROUND: In patients with localized pancreatic ductal adenocarcinoma (PDAC) undergoing neoadjuvant therapy (NAT) and resection, selection of adjuvant chemotherapy (AC) is typically guided by high-risk features on histopathologic examination. We evaluated the interaction between post-NAT lymph node metrics and AC receipt on survival. METHODS: Patients who received NAT followed by pancreatectomy (2010-2020) at seven centers were reviewed. Overall survival (OS) in patients receiving AC or not was stratified by lymph node positivity (LNP) or lymph node ratio (LNR) dichotomized at 0.1. Cox models evaluated the independent association between these nodal metrics, AC receipt, and OS. RESULTS: Of 464 patients undergoing NAT and resection, 264 (57%) received AC. Patients selected for AC were younger (median 63 vs. 67 years; p < 0.001), received shorter duration of NAT (2.8 vs. 3.2 months; p = 0.01), had fewer postoperative complications (Clavien-Dindo grade > 3: 1.2% vs. 11.7%; p < 0.001), and lower rates of pathologic complete response (4% vs. 11%; p = 0.01). The median number of nodes evaluated was similar between cohorts (n = 20 in both; p = 0.9). Post-NAT LNP rates were not different, and median LNR was 0.1, in AC and non-AC cohorts. Both LNP (hazard ratio [HR]: 2.1, p < 0.001) and LNR (0 < LNR ≤ 0.1: HR: 1.98, p = 0.002; LNR > 0.1: HR 2.46, p < 0.001) were independently associated with OS on Cox modeling, although receipt of AC was not associated with improved OS (median 30.6 vs. 29.4 months; p = 0.2). In patients with LNR > 0.1, receipt of AC was associated with significantly longer OS compared to non-AC (24 vs. 20 months, respectively; p = 0.04). CONCLUSIONS: LNR following NAT, not simply nodal positivity, may be useful to refine selection of AC in resected PDAC.

Mirror Syndrome Combined with Postpartum Hemolytic Uremic Syndrome.

BACKGROUND: Mirror syndrome is a rare disease characterized by "triple edema", while Hemolytic Uremic Syndrome (PHUS) is a serious disease that occurs within a short period of time after the end of pregnancy, with a low prevalence and poor prognosis, and it is even rarer for both to occur in the same patient. METHODS: We report a case of mirror syndrome combined with PHUS and analyze the clinical data to improve the understanding of the disease. RESULTS: The patient presented clinically with "triple edema" and was diagnosed with mirror image syndrome. After cesarean section, the patient developed cardiac insufficiency, renal insufficiency, hemolysis, and other symptoms and was diagnosed as PHUS. After active treatment, the maternal prognosis was good. CONCLUSIONS: Mirror syndrome and PHUS are both clinically rare diseases with poor long-term prognosis if not diagnosed and treated in a timely manner; therefore, awareness of the diseases, early and accurate diagnosis and timely and correct treatment should be improved.

FBXO28 reduces high-fat diet-induced hyperlipidemia in mice by alleviating abnormal lipid metabolism and inflammatory responses.

BACKGROUND: Hyperlipidemia is a lipid metabolism disorder with increasing incidence and prevalence worldwide. Abnormal lipid metabolism and inflammation are two significant characteristics of hyperlipidemia. The purpose of this study was to explore the role and mechanism of F-box only protein 28 (FBXO28) in hyperlipidemia. METHODS: Mice were fed with high-fat diet (HFD) to elicit obesity, and 3T3-L1 preadipocytes were stimulated with MDI cocktail (IBMX, DEX and insulin) to evoke differentiation. In vivo and in vitro role of FBXO28 in hyperlipidemia was investigated by hematoxylin-eosin and oil Red O staining, the lipid biochemistry measurement, enzyme-linked immunosorbent assay, reverse transcription quantitative polymerase chain reaction and western blotting assays. The mechanism of FBXO28 explored by co-immunoprecipitation, immunofluorescence, ubiquitination and cycloheximide assays. RESULTS: Low expression of FBXO28 was found in hyperlipidemia in silico, in vivo and in vitro. Upregulation of FBXO28 declined the body weight, fat accumulation, and serum lipid content in HFD-fed mice. Abnormal lipid accumulation, and the level of liposynthetic genes and beta-oxidation related genes were improved by overexpression of FBXO28 both in HFD-elicited mice and MDI-treated 3T3-L1 preadipocytes. Besides, overexpression of FBXO28 declined HFD-induced the level of proinflammatory factors and F4/80. Mechanically, FBXO28 directly bound RAB27A and promoted its ubiquitinated degradation. Thus, upregulation of RAB27A inverted the improved role of FBXO28 in abnormal lipid metabolism and inflammation in vivo and in vitro. CONCLUSION: FBXO28 ameliorated abnormal lipid metabolism and inflammation through the ubiquitinated degradation of RAB27A, thereby attenuating HFD-induced hyperlipidemia. The results could promote the treatment of hyperlipidemia, and the relevant diseases.

Osteoporosis is associated with depression among older adults: a nationwide population-based study in the USA from 2005 to 2020.

OBJECTIVES: The global prevalence of osteoporosis is rising, yet it is unclear whether people with osteoporosis have a higher risk of depression than those without osteoporosis. STUDY DESIGN: A cross-sectional study. METHODS: We used nationally representative data from the US National Health and Nutrition Examination Survey (NHANES) in 2005-2006, 2007-2008, 2009-2010, 2013-2014, and 2017-2020. The diagnosis of osteoporosis was based on the bone mineral density of the femoral neck measured by dual-energy X-ray absorptiometry. Depression was assessed by the Patient Health Questionnaire-9 (PHQ-9), with a score ≥5 as depressive symptoms and a score ≥10 as probable depression. We used logistic regression models to evaluate the association between osteoporosis and depressive symptoms and probable depression. RESULTS: We included 11,603 adults (aged 50 years and older, 52.3% male) and observed 5.2% of them had osteoporosis. 31.9% of these osteoporotic people had depressive symptoms, and 10.0% had probable depression. Compared to participants without osteoporosis, those with osteoporosis were 1.73 times more likely to experience depressive symptoms (odds ratio [OR] = 1.73, 95% confidence interval [CI] 1.20-2.50) and 1.91 times more likely to experience probable depression (OR = 1.91, 95% CI 1.02-3.59), after adjusting for sex, age, race/ethnicity, education, marital status, family income, body mass index, smoking, physical activity, and alcohol abuse. Moderate-to-vigorous activities mediated the associations between osteoporosis and depression and depressive symptoms. CONCLUSIONS: Osteoporosis is an independent risk factor for depression. This study highlights the need to evaluate the mental well-being of patients with osteoporosis in clinical and primary health care.

Socio-economic factors and medical conditions affecting regular stomach cancer screening in Korea: a retrospective longitudinal study using national public health data for 11 years.

OBJECTIVE: This study aimed to explore socio-economic factors and medical conditions that affect regular stomach cancer (SC) screening among Korean adults. STUDY DESIGN: This was a retrospective observational study. METHODS: Study subjects were 5545 adults aged ≥40 years who participated in the 2007-2012 Korean National Health and Nutrition Examination Survey and were followed up to year 2017 based on data linking to the Korean National Health Insurance Service and Korean Health Insurance Review and Assessment. Socio-economic factors included sex, age, residential area, education, occupation, marital status, disability, public and private health insurance, service through local public health organizations, history of cancer except for SC, and family history of SC. Medical factors included six gastric lesions with the possibility of facilitating SC screening, including benign gastric neoplasm, chronic atrophic gastritis, gastric polyp, Helicobacter pylori infection, intestinal metaplasia, and peptic ulcers. The outcome was adherence to SC screening, which was divided into non-adherence, irregular adherence, and regular adherence. RESULTS: After adjusting for the effects of socio-economic factors, multivariate ordinal logistic regression revealed that participants with a history of four types of gastric lesions were more likely to regularly participate in SC screening: chronic atrophic gastritis (odds ratio [OR] 1.567; 95% confidence interval [CI] = 1.276-1.923), gastric polyps (OR 1.565; 95% CI = 1.223-2.003), H. pylori infection (OR 1.637; 95% CI = 1.338-2.003), and peptic ulcer (OR 2.226; 95% CI 1.750-2.831). CONCLUSIONS: To improve participation in SC screening, it is necessary to implement personalized strategies for individuals at risk for gastric cancer in addition to population-based strategies for vulnerable groups.

[Comparison of clinical characteristics in intermittent exotropia patients with different visual perception and oculomotor control].

Objective: To explore the clinical characteristics of intermittent exotropia (IXT) patients with different visual perception and oculomotor control. Methods: A cross-sectional study was conducted. Minor IXT patients between March 2021 and May 2023 at Beijing Tongren Hospital were enrolled. Demographic characteristics were recorded, and visual perception and oculomotor control were evaluated. The patients were divided into simultaneous vision disappearing and existing groups, fusion disappearing and existing groups, distant stereoscopic vision disappearing and normal groups, and near stereoscopic vision injury and normal groups. Statistical description was performed by using M (Q1, Q3). Rank sum test was used to compare the Revised Newcastle Control Score (RNCS), near and far strabismus degree, duration of disease, and age of onset among different groups. The correlation between visual perception and oculomotor control and the correlation of duration of disease and age of onset with visual perception and oculomotor control were analyzed by Pearson correlation analysis. Results: A total of 381 patients were enrolled, including 189 males and 192 females, with a median age of 7 (6, 9) years. The incidence of normal visual perception was 19.4% (74/381). Compared with simultaneous vision and fusion existing groups and distant and near stereoscopic vision normal groups, the RNCS [7 (5, 9) vs 4 (3, 6), 6 (5, 8) vs 4 (3, 6), 5 (4, 7) vs 3 (3, 5), and 5 (3, 6) vs 4 (3, 6)], near strabismus degree [65Δ (60Δ, 80Δ) vs 40Δ (30Δ, 50Δ), 60Δ (45Δ, 65Δ) vs 40Δ (30Δ, 50Δ), 50Δ (40Δ, 60Δ) vs 35Δ (30Δ, 45Δ), and 45Δ (30Δ, 60Δ) vs 40Δ (30Δ, 50Δ)] and far strabismus degree [60Δ (50Δ, 75Δ) vs 35Δ (25Δ, 50Δ), 55Δ (41Δ, 65Δ) vs 35Δ (25Δ, 45Δ), 45Δ (30Δ, 60Δ) vs 35Δ (25Δ, 45Δ), and 40Δ (30Δ, 60Δ) vs 35Δ (25Δ, 45Δ)] increased significantly in disappearing simultaneous vision, fusion, and distant stereoscopic vision groups and injury near stereoscopic vision group (all P<0.05). Compared with simultaneous vision and fusion existing groups and distant stereoscopic vision normal group, duration of disease was significant longer in disappearing simultaneous vision, fusion, and distant stereoscopic vision groups [3 (1, 5) years vs 2 (1, 3) years, 2 (1, 4) years vs 1 (1, 3) years, 2 (1, 4) years vs 1 (1, 3) years, all P<0.05]. The age of onset in disappearing distant stereoscopic vision group was significantly lower than normal distant stereoscopic vision group [5 (3, 7) years vs 6 (4, 8) years, P=0.005]. Pearson correlation analysis showed that subjective angle and random dot stereogram (RDS) stereoacuity were positive correlation with RNCS, and the near and far strabismus degree (r=0.414, 0.516, and 0.559, all P<0.001; r=0.153, 0.142, and 0.173, all P<0.05). Subjective angle, RNCS, and the near and far strabismus degree were positive correlation with duration of disease (r=0.238, 0.195, 0.236, 0.239, all P<0.001) and negative correlation with age of onset (r=-0.184, -0.279, -0.112, -0.147, all P<0.05). Conclusions: Nearly 20% of IXT patients have normal visual perception. With the longer duration of disease or lower age of onset, the incidence of abnormal visual perception is higher and injury of visual perception and oculomotor control is more serious.

[Quantitative comparison of binocular suppression of patients with anisometropic amblyopia and ametropic amblyopia].

Objective: To explore the differences in clinical characteristics and interocular interactions between patients with anisometropic amblyopia and ametropic amblyopia. Methods: Cross-sectional study. The newly diagnosed anisometropic (the binocular difference in spherical equivalent≥1.00 D) amblyopia patients and ametropic amblyopia patients (aged 4 to 6 years) in Beijing Tongren Hospital from January 2020 to December 2022 were involved. Patients were further categorized by the refractive status after cycloplegia, including hyperopia, myopia, astigmatism, hyperopia with astigmatism, myopia with astigmatism, mild anisometropia and severe anisometropia. Quantitative measurements of best-corrected visual acuity (logMAR), stereoacuity (transformed to log units), perceptual eye position and interocular suppression were performed, and the differences between groups were analyzed. The rank sum test was used for statistical evaluation. Results: The average age of 45 ametropic amblyopia patients (21 males and 24 females) and 84 anisometropic amblyopia patients (48 males and 36 females) was 5.0 (4.0, 5.0) years and 5.0 (4.0, 6.0) years, respectively. The interocular differences in spherical equivalent [2.56 (1.50, 4.19) D vs. 0.25 (0.13, 0.56) D] and best-corrected visual acuity [0.40 (0.18, 0.70) logMAR vs. 0.07 (0.00, 0.12) logMAR] were larger in patients with anisometropic amblyopia than those with ametropic amblyopia. The anisometropic amblyopia patients had worse stereoacuity [2.60 (2.00, 2.90) log arcsec vs. 2.00 (2.00, 2.30) log arcsec] and deeper suppression [20.0% (13.3%, 40.0%) vs. 10.0% (0, 23.3%)], compared with the ametropic amblyopia patients. The differences were all statistically significant (P<0.05). The suppression and stereoacuity between patients with hyperopic anisometropic amblyopia [suppression, 30.0% (17.5%, 50.0%); stereoacuity, 2.90 (2.30, 2.90) log arcsec] and astigmatic anisometropic amblyopia [suppression, 10.0% (0, 20.0%); stereoacuity, 2.00 (2.00, 2.30) log arcsec] were significantly different (P<0.05). The differences of suppression and stereoacuity between patients with severe (binocular difference in spherical equivalent>2.50 D) [suppression, 30.0% (20.0%, 53.3%); stereoacuity, 2.90 (2.57, 2.90) log arcsec] and mild anisometropia [suppression, 20.0% (0, 30.0%); stereoacuity, 2.00 (2.00, 2.90) log arcsec] were also statistically significant (P<0.05). Conclusions: Patients with anisometropic amblyopia have deeper binocular suppression, worse stereoacuity and more severe binocular interaction abnormality than those with ametropic amblyopia. The severity of anisometropia affects the degree of the interaction abnormality.

[Clinical characteristics of acute macular neuroretinopathy in China associated with COVID-19 infection].

Objective: To investigate the clinical features of acute macular neuroretinopathy (AMN) following coronavirus disease 2019 (COVID-19). Methods: This retrospective case series study included 15 patients (28 eyes) diagnosed with AMN at the Department of Ophthalmology, Peking University Third Hospital, from November 2022 to January 2023. The AMN group comprised 4 males and 11 females, with a mean age of (31.36±8.08) years. A control group of 15 individuals [5 males, 10 females; mean age (33.20±5.10) years] who had COVID-19 but did not develop AMN was also included. Data collected for all patients included best-corrected visual acuity (BCVA), slit-lamp examination, dilated fundus examination, color fundus photography, fluorescein fundus angiography (FFA), and optical coherence tomography (OCT) results. Serum cytokine levels, including interleukins (ILs), interferons (IFNs), and tumor necrosis factor-alpha (TNF-α), were measured for both groups. Results: Among the 28 eyes, severe vision loss (BCVA≤0.3) was observed in 3 eyes (10.7%), moderate vision loss (BCVA>0.3 and≤0.5) in 2 eyes (13.3%), and mild vision loss (BCVA>0.5 and≤1.0) in 23 eyes (82.1%). OCT findings in all 28 eyes revealed hyperreflectivity of the outer nuclear layer and disruption of outer retinal structure. Additionally, 3 eyes (10.7%) exhibited cotton wool spots in the posterior pole, 2 eyes (7.1%) showed mild cystoid macular edema with intraretinal hyperreflective dots, and 1 eye (3.6%) presented with paracentral acute middle maculopathy. FFA indicated retinal vasculitis in 2 cases (4 eyes, 14.3%). Serum levels of IL-4, IL-5, IFN-α, and IFN-γ were significantly higher in the AMN group compared to the control group: IL-4 [4.49 (3.66, 6.08) vs. 1.40 (0.62, 1.68) pg/ml], IL-5 [7.34 (5.04, 14.06) vs. 0.17 (0.11, 1.86) pg/ml], IFN-α [8.42 (6.31, 14.89) vs. 0.50 (0.30, 0.83) pg/ml], and IFN-γ [17.93 (12.75, 32.44) vs. 7.43 (0.00, 14.74) pg/ml], with all differences being statistically significant (all P<0.05). Conclusion: AMN following COVID-19 can present with wedge-shaped dark red lesions in the macular area, often accompanied by cotton wool spots and retinal vasculitis. Additionally, there is a significant elevation in various inflammatory cytokines in the serum.

[Risk factors of cytomegalovirus infection in patients with failed corneal grafts].

Objective: To investigate the levels of cytomegalovirus (CMV) infection and associated risk factors in corneal transplant recipients who experienced transplant failure. Methods: This was a case-control study. Clinical data from 576 cases (576 eyes) of patients who underwent repeat corneal transplant surgery at the Department of Ophthalmology, Peking University Third Hospital, due to corneal transplant failure from January 2016 to May 2022 were collected. Of these, 305 were male and 271 were female, with a median age of 44.0 (0.7, 91.0) years. The CMV infection rate was analyzed based on the detection of CMV DNA in aqueous humor or corneal tissue during corneal transplant surgery. Patients were divided into the CMV group (CMV DNA positive) and the control group (herpes virus DNA negative). The main research indicators included the CMV infection rate, clinical characteristics, and risk factors in corneal transplant recipients. Chi-square tests and binary logistic analysis were used to compare differences between the two groups in general information, systemic diseases, ocular lesions, ocular surgical history, and local and systemic medications. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for each CMV infection risk factor. Results: The overall CMV infection rate was 21.9%(126/576), with annual rates ranging from 10.9% to 37.7% from 2016 to 2021. After applying inclusion and exclusion criteria, 378 patients were included in the control trial, with 126 in the CMV group and 252 in the control group. Statistically significant differences between the two groups were observed in systemic immune-related corneal lesions [CMV group: 38 (30.2%), control group: 26 (10.3%)], local immune and inflammatory corneal lesions [CMV group: 46 (36.5%), control group: 40 (15.9%)], congenital corneal opacity [CMV group: 46 (36.5%), control group: 48 (19.0%)] total number of corneal transplants (CMV group: 178 times, control group: 276 times), corneal deep neovascularization crossing the graft [CMV group: 104 (82.5%), control group: 68 (27.0%)] and severe opacity [CMV group: 44 (34.9%), control group: 30 (11.0%)]. Binary logistic regression analysis showed that systemic immune-related corneal lesions (OR=4.044, 95%CI 1.810-9.033, P<0.001), local immune and inflammatory corneal lesions (OR=3.554, 95%CI 1.569-8.052, P=0.002), congenital corneal opacity (OR=2.606, 95%CI 1.216-5.589, P=0.014), total number of corneal transplants (OR=3.206, 95%CI 1.753-5.864, P<0.001), corneal deep neovascularization crossing the graft (OR=8.347, 95%CI 3.967-17.559, P<0.001), and severe opacity (OR=3.063, 95%CI 1.221-7.682, P=0.017) were independent risk factors for CMV infection after corneal transplant. Conclusions: CMV infection was present in more than 1/5 of corneal transplant recipients who experienced transplant failure. CMV infection after corneal transplant may be related to immune rejection reactions and ocular inflammatory responses. Inflammatory corneal lesions associated with systemic or local immune abnormalities, congenital corneal opacity, and multiple corneal transplants may exacerbate the levels of inflammatory factors during the perioperative period of corneal transplant, increasing the risk of post-transplant CMV infection, leading to the infiltration of deep neovascularization and severe opacity in the cornea.

Racial Disparity in Pathologic Response following Neoadjuvant Chemotherapy in Resected Pancreatic Cancer: A Multi-Institutional Analysis from the Central Pancreatic Consortium.

BACKGROUND: Major pathologic response (MPR) following neoadjuvant therapy (NAT) in pancreatic ductal adenocarcinoma (PDAC) patients undergoing resection is associated with improved survival. We sought to determine whether racial disparities exist in MPR rates following NAT in patients with PDAC undergoing resection. METHODS: Patients with potentially operable PDAC receiving at least 2 cycles of neoadjuvant FOLFIRINOX or gemcitabine/nab-paclitaxel ± radiation followed by pancreatectomy (2010-2019) at 7 high-volume centers were reviewed. Self-reported race was dichotomized as Black and non-Black, and multivariable models evaluated the association between race and MPR (i.e., pathologic complete response [pCR] or near-pCR). Cox regression evaluated the association between race and disease-free (DFS) and overall survival (OS). RESULTS: Results of 486 patients who underwent resection following NAT (mFOLFIRINOX 56%, gemcitabine/nab-paclitaxel 25%, radiation 29%), 67 (13.8%) patients were Black. Black patients had lower CA19-9 at diagnosis (median 67 vs. 204 U/mL; P = 0.003) and were more likely to undergo mild/moderate chemotherapy dose modification (40 vs. 20%; P = 0.005) versus non-Black patients. Black patients had significantly lower rates of MPR compared with non-Black patients (13.4 vs. 25.8%; P = 0.039). Black race was independently associated with worse MPR (OR 0.26, 95% confidence interval [CI] 0.10-0.69) while controlling for NAT duration, CA19-9 dynamics, and chemotherapy modifications. There was no significant difference in DFS or OS between Black and non-Black cohorts. CONCLUSIONS: Black patients undergoing pancreatectomy appear less likely to experience MPR following NAT. The contribution of biologic and nonbiologic factors to reduced chemosensitivity in Black patients warrants further investigation.

Lymph node metastases in young patients with gastrointestinal stromal tumor: A nationwide analysis.

BACKGROUND: Children, adolescents, and young adults (CAYA) (age ≤39 years) with GIST have high rates of LNM, but their clinical relevance is undefined. This study analyzed the impact of LNM on overall survival (OS) for CAYA with GIST. METHODS: The National Cancer Database was queried for patients with resected GIST and pathologic nodal staging data from 2004-2019. Factors associated with LNM were identified. Survival was assessed stratified by presence of LNM. RESULTS: Of 4420 patients with GIST, 238 were CAYA (5.4%). When compared to older adults, CAYA more often had small intestine primaries (51.8% vs. 36.6%, p < 0.0001), T4 tumors (30.7% vs. 24.5%, p = 0.0275) and pN1 disease (11.3% vs. 4.7%, p < 0.0001). Within a multivariable Cox proportional hazards regression model adjusting for age, comorbid disease, mitotic rate, tumor size, and primary site, LNM were associated with increased hazard of death for older adults (hazard ratio [HR]: 1.83; confidence interval [CI]: 1.35-2.42; p < 0.0001), but not CAYA (HR: 3.38; CI: 0.50-14.08; p = 0.13). For CAYA, only high mitotic rate predicted mortality (HR: 4.68; CI: 1.41-18.37: p = 0.02). CONCLUSIONS: LNM are more commonly identified among CAYA with resected GIST who undergo lymph node evaluations, but do not appear to impact OS as observed in older adults. High mitotic rate remains a predictor of poor outcomes for CAYA with GIST.

Placental biomarkers and fetoplacental Dopplers in combination reliably predict preterm birth in pregnancies complicated by fetal growth restriction.

OBJECTIVE: To assess the association between placental biomarkers (placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio) and fetoplacental Dopplers - Umbilical Artery Pulsatility Index (UA PI) and Uterine Artery Pulsatility Index (UtA PI) in various combinations for the likelihood of preterm birth (PTB) in women with fetal growth restriction (FGR). METHODS: A prospective cohort study of pregnancies complicated by FGR. Maternal serum PlGF levels, sFlt-1/PlGF ratio, UA PI and UtA PI were measured at 4-weekly intervals from recruitment to delivery. Harrell's concordance statistic was used to evaluate various combinations of placental biomarkers and fetoplacental Dopplers to ascertain the ideal combination to predict PTB (<37 weeks). Multivariable Cox regression was used as time-varying covariates. RESULTS: There were 320 pregnancies in the study cohort - 179 (55.9%) were FGR and 141 (44.1%) were AGA. In the FGR cohort, both low PlGF levels and elevated sFlt-1/PlGF ratio significantly affected time to PTB. Low PlGF was a better predictor of PTB than either sFlt-1/PlGF ratio or combination of PlGF and sFlt-1/PlGF ratio (Harrell's C 0.81, 0.79, 0.75 respectively). Similarly, although both UA PI and UtA PI >95th centile for gestation significantly affected the time to PTB, in combination, they were better predictors than either measure alone (Harrell's C 0.82, 0.75, 0.76 respectively). The predictive utility was highest when PlGF <100ng/L, UA PI and UtA PI >95th centile was combined (Harrell's C 0.88) (HR 32.99 95% CI 10.74, 101.32). CONCLUSIONS: Low maternal PlGF levels (<100ng/L) and abnormal fetoplacental Dopplers (UA PI and UtA PI >95th centile) in combination have greatest predictive utility for PTB in pregnancies complicated with FGR and may help guide clinical management of these complex pregnancies. This article is protected by copyright. All rights reserved.

The role of Ca2+ and protein scaffolding in the formation of nature's water oxidizing complex.

Photosynthetic O2 evolution is catalyzed by the Mn4CaO5 cluster of the water oxidation complex of the photosystem II (PSII) complex. The photooxidative self-assembly of the Mn4CaO5 cluster, termed photoactivation, utilizes the same highly oxidizing species that drive the water oxidation in order to drive the incorporation of Mn2+ into the high-valence Mn4CaO5 cluster. This multistep process proceeds with low quantum efficiency, involves a molecular rearrangement between light-activated steps, and is prone to photoinactivation and misassembly. A sensitive polarographic technique was used to track the assembly process under flash illumination as a function of the constituent Mn2+ and Ca2+ ions in genetically engineered membranes of the cyanobacterium Synechocystis sp. PCC6803 to elucidate the action of Ca2+ and peripheral proteins. We show that the protein scaffolding organizing this process is allosterically modulated by the assembly protein Psb27, which together with Ca2+ stabilizes the intermediates of photoactivation, a feature especially evident at long intervals between photoactivating flashes. The results indicate three critical metal-binding sites: two Mn and one Ca, with occupation of the Ca site by Ca2+ critical for the suppression of photoinactivation. The long-observed competition between Mn2+ and Ca2+ occurs at the second Mn site, and its occupation by competing Ca2+ slows the rearrangement. The relatively low overall quantum efficiency of photoactivation is explained by the requirement of correct occupancy of these metal-binding sites coupled to a slow restructuring of the protein ligation environment, which are jointly necessary for the photooxidative trapping of the first stable assembly intermediate.

[Microanatomy and functional MRI study of arcuate fasciculus and superior longitudinal fasciculus].

Objectives: To explore the microanatomy and functional MRI(fMRI) of arcuate fasciculus(AF) and superior longitudinal fasciculus(SLF),and to analyze their functions. Methods: Ten normal adult cadaveric head specimens (20 cerebral hemispheres) were fixed with 10% methanal at the Translational Research Institute for Neurological Disorders of the Wannan Medical Collegefrom February to December 2022.The Klingler fiber dissection technique was utilized to perform white matter fiber dissection,with a magnification ranging from 6 to 40.The study focused on the microanatomical structures of the AF and SLF,aiming to explore their relationships with deep brain fibers.Furthermore, six healthy adult volunteers who underwent fMRI of the brain were included.The collected diffusion tensor imaging (DTI) data were processed and integrated with the microanatomical findings for a comprehensive analysis. Results: After removing the gray matter of the cerebral cortex,the superficial U fibers were exposed.The long association fibers that beneath the U fibers were the AF and SLF,which were the main long association fibers in the superficial layers of the brain.The AF could be divided into dorsal and ventral parts,while the SLF could be divided into Ⅰ,Ⅱ,and Ⅲ.SLF Ⅰ lied within the upper bank of the cingulate sulcus,travels medial to the callosal sulcus.The SLF Ⅱ,Ⅲ,and the AF were located on the lateral surface of the brain.By removing the gray matter of the insular cortex and the extreme capsule,exposing the external capsule and claustrum.Subsequently,the AF and SLF Ⅱ,Ⅲ were dissected,revealing the corona radiata and sagittal stratum,along with other deep brain fibers.During the dissection,it was observed that there was a close connection between the AF,SLF Ⅱ,and the deep brain fibers.Furthermore,in the regions above the lateral fissure of the cerebral hemisphere,there was no direct connection of long association fibers between the gray matter cortex and the deep U fibers in the coronal plane.These findings were further supported by DTI studies. Conclusions: The AF and SLF are the major long association fibers that located in the superficial layers of the brain,and closely connect to the gray matter cortex and U fibers,even closely relate with deep brain fibers.In the regions above the lateral fissure of the hemisphere,only the AF and SLF Ⅱ and Ⅲ serve as superficial long association fibers in the anterior-posterior direction.These fibers are likely involved in the transmission of brain functional information between the top and bottom gray matter cortex in the coronal plane above the lateral fissure.

[Efficacy evaluation of 0.05% cyclosporine A and 0.1% tacrolimus eye drops in the treatment of severe dry eye associated with chronic graft-versus-host disease].

Objective: To evaluate the effectiveness and safety of 0.05% cyclosporine A and 0.1% tacrolimus eye drops in treating severe dry eye associated with chronic graft-versus-host disease (cGVHD). Methods: This non-randomized concurrent control trial enrolled 83 eyes from 83 patients with cGVHD-associated severe dry eye. The treatment had two phases. During the initial shock treatment period (0-3 months), 44 patients received 0.05% cyclosporine A eye drops (4 times/day; group A) and 39 patients received 0.1% tacrolimus eye drops (twice/day; group B) alongside basic treatment. In the maintenance treatment period (3-6 months), both groups used 0.05% cyclosporine A eye drops (twice/day) and sodium hyaluronate. Examinations were conducted at 1, 3, and 6 months after treatment initiation, assessing the Ocular Surface Disease Index (OSDI), corneal fluorescein staining (CFS) score, and fluorescein tear break-up time (BUT) for efficacy. visual acuity and intraocular pressure (IOP) were evaluated for safety, and patients' post-medication irritation symptoms were recorded. Results: The study included 52 males and 31 females, aged (28.57±15.67) years. After 1 month of treatment, the CFS score in group A significantly decreased from 10.0 (6.0, 14.0) to 5.0 (3.0, 8.5) (P<0.001). in group B, the CFS score also significantly decreased from 10.0 (6.0, 15.0) to 6.0 (2.0, 10.0), and the BUT increased from 2.0 (1.0, 2.0) s to 2.0 (1.8, 3.3) s (P<0.001). No significant OSDI decrease was observed in either group. No significant differences were found in OSDI, CFS score, and BUT between the two groups. After 3 months, group A showed significant improvement in OSDI, CFS score, and BUT (P<0.05), while group B only demonstrated significant CFS score decrease (P<0.05). OSDI was significantly lower in group A than group B (P<0.05). No significant differences were noted in CFS score and BUT between groups. After 6 months, OSDI, CFS score, and BUT were 18.9 (9.3, 34.2), 7.0 (3.0, 8.5), and 2.0 (1.0, 3.0) s in group A, and 10.9 (3.6, 35.4), 5.5 (2.8, 10.0), and 2.0 (1.0, 10.0) s in group B. In both groups, CFS scores significantly decreased and BUT increased (P<0.05). Visual acuity improved significantly in group A at 1, 3, and 6 months (P<0.05), while no significant changes were seen in group B. Irritation symptoms were transient and self-resolving in both groups. Conclusions: Both 0.05% cyclosporine A and 0.1% tacrolimus eye drops, when combined with local glucocorticoids, exhibited significant anti-inflammatory effects, effectively and safely treating severe dry eye in cGVHD patients. Although the onset of 0.05% cyclosporine A was slower than 0.1% tacrolimus, it offered more stable long-term effects and better symptom improvement.

[A multicenter clinical trial of collar-button type keratoprosthesis implantation for the treatment of corneal blindness in high-risk transplantation].

Objective: To evaluate the efficiency and safety of collar-button type keratoprosthesis (c-bKPro) implantation for corneal blindness in high-risk transplantation in China. Methods: It was a case series study. High-risk corneal blind patients who planned to undergo c-bKPro implantation were prospectively and continuously enrolled in the Eye Hospital of Shandong First Medical University, Ophthalmology Division of Chinese PLA General Hospital, Zhongshan Ophthalmic Center, Department of Ophthalmology in Eye & ENT Hospital of Fudan University, and Eye Hospital of Wenzhou Medical University from July 2019 to January 2020. The cure for blindness and surgical success were assessed based on visual acuity (VA)≥0.05. The complications and keratoprosthesis retention rate were recorded to determine the safety of the surgery. Results: Thirty-seven subjects (eyes) were included, of which 32 were male and 5 were female, aged 27 to 72 years old. The indications of c-bKPro implantation were corneal graft failure (21 eyes, 56.8%), chemical injury (8 eyes, 21.6%), thermal burn (5 eyes, 13.5%), unexplained corneal opacity (2 eyes, 5.4%), and corneal perforation (1 eye, 2.7%). Two patients withdrew from the clinical trial at 3 months postoperatively. Thirty-five patients were followed up for 6 months, and 31 were followed up for 12 months. The VA was ≥0.05 in 83.8% of eyes at 6 months and in 81.8% of eyes at 12 months. Among the 11 eyes diagnosed with concurrent glaucoma, 6 eyes achieved a VA of ≥0.05. At 12 months, the c-bKPro retention rate was 100%. The surgical complications included retroprosthetic membrane formation (5 eyes, 16.1%), persistent corneal epithelial defects (5 eyes, 16.1%), macular edema (4 eyes, 12.9%), new-onset glaucoma (4 eyes, 12.5%; including one eye withdrawn from the study at 3 months), sterile corneal melting (2 eyes, 6.5%), sterile vitritis (1 eye, 3.2%), and infectious keratitis (1 eye, 3.2%). Conclusions: C-bKPro implantation is an effective and safe option for treating corneal blindness in high-risk transplantation in China. Improved visual outcomes could be achieved in most cases, with a relatively low incidence of postoperative complications.

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

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

Regulatory Small RNA Qrr2 Is Expressed Independently of Sigma Factor-54 and Can Function as the Sole Qrr Small RNA To Control Quorum Sensing in Vibrio parahaemolyticus.

Bacterial cells alter gene expression in response to changes in population density in a process called quorum sensing (QS). In Vibrio harveyi, LuxO, a low-cell-density activator of sigma factor-54 (RpoN), is required for transcription of five noncoding regulatory small RNAs (sRNAs), Qrr1 to Qrr5, which each repress translation of the master QS regulator, LuxR. Vibrio parahaemolyticus, the leading cause of bacterial seafoodborne gastroenteritis, also contains five Qrr sRNAs that control OpaR (the LuxR homolog), controlling capsule polysaccharide (CPS), motility, and metabolism. We show that in a ΔluxO deletion mutant, opaR was derepressed and CPS and biofilm were produced. However, in a ΔrpoN mutant, opaR was repressed, no CPS was produced, and less biofilm production was observed than in the wild type. To determine why opaR was repressed, expression analysis in ΔluxO showed that all five qrr genes were repressed, while in ΔrpoN the qrr2 gene was significantly derepressed. Reporter assays and mutant analysis showed that Qrr2 sRNA can act alone to control OpaR. Bioinformatics analysis identified a sigma-70 (RpoD) -35 -10 promoter overlapping the canonical sigma-54 (RpoN) -24 -12 promoter in the qrr2 regulatory region. The qrr2 sigma-70 promoter element was also present in additional Vibrio species, indicating that it is widespread. Mutagenesis of the sigma-70 -10 promoter site in the ΔrpoN mutant background resulted in repression of qrr2. Analysis of qrr quadruple deletion mutants, in which only a single qrr gene is present, showed that only Qrr2 sRNA can act independently to regulate opaR. Mutant and expression data also demonstrated that RpoN and the global regulator, Fis, act additively to repress qrr2. Our data have uncovered a new mechanism of qrr expression and show that Qrr2 sRNA is sufficient for OpaR regulation. IMPORTANCE The quorum sensing noncoding small RNAs (sRNAs) are present in all Vibrio species but vary in number and regulatory roles among species. In the Harveyi clade, all species contain five qrr genes, and in Vibrio harveyi these are transcribed by sigma-54 and are additive in function. In the Cholerae clade, four qrr genes are present, and in Vibrio cholerae the qrr genes are redundant in function. In Vibrio parahaemolyticus, qrr2 is controlled by two overlapping promoters. In an rpoN mutant, qrr2 is transcribed from a sigma-70 promoter that is present in all V. parahaemolyticus strains and in other species of the Harveyi clade, suggesting a conserved mechanism of regulation. Qrr2 sRNA can function as the sole Qrr sRNA to control OpaR.

Intraoperative Pancreatic Neck Margin Assessment During Pancreaticoduodenectomy for Pancreatic Adenocarcinoma in the Era of Neoadjuvant Therapy: A Multi-institutional Analysis from the Central Pancreatic Consortium.

BACKGROUND: Data regarding the survival impact of converting frozen-section (FS):R1 pancreatic neck margins to permanent section (PS):R0 by additional resection (i.e., converted-R0) during upfront pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) are conflicting. The impact of neoadjuvant therapy on this practice and its relationship with overall survival (OS) is incompletely understood. METHODS: We reviewed PDAC patients (80% borderline resectable/locally advanced [BR/LA]) undergoing pancreaticoduodenectomy after neoadjuvant therapy at seven, academic, high-volume centers (2010-2018). Multivariable models examined the association of PS:R0, PS:R1, and converted-R0 margins with OS. RESULTS: Of 272 patients receiving at least 2 (median 4) cycles of neoadjuvant chemotherapy (71% mFOLFIRINOX or gemcitabine/nab-paclitaxel) and undergoing pancreaticoduodenectomy with intraoperative frozen-section assessment of the transected pancreatic neck margin, PS:R0 (n = 220, 80.9%) was observed in a majority of patients; 18 patients (6.6%) had converted-R0 margins following additional resection, whereas 34 patients (12.5%) had persistently positive PS:R1 margins. At a median follow-up of 42 months, PS:R0 resection was associated with improved OS compared with either converted-R0 or PS:R1 resection (median 25 vs. 14 vs. 16 months, respectively; p = 0.023), with no survival difference between the converted-R0 and PS:R1 groups (p = 0.9). On Cox regression, SMA margin positivity (hazard ratio 2.2, p = 0.012), but not neck margin positivity (hazard ratio 1.2, p = 0.65), was associated with worse OS. CONCLUSIONS: In this multi-institutional cohort of predominantly BR/LA PDAC patients undergoing pancreaticoduodenectomy following modern neoadjuvant therapy, pursuing a negative neck margin intraoperatively if the initial margin is positive does not appear to be associated with improved survival.

Urban Water Storage Capacity Inferred From Observed Evapotranspiration Recession.

Water storage plays an important role in mitigating heat and flooding in urban areas. Assessment of the water storage capacity of cities remains challenging due to the inherent heterogeneity of the urban surface. Traditionally, effective storage has been estimated from runoff. Here, we present a novel approach to estimate effective water storage capacity from recession rates of observed evaporation during precipitation-free periods. We test this approach for cities at neighborhood scale with eddy-covariance based latent heat flux observations from 14 contrasting sites with different local climate zones, vegetation cover and characteristics, and climates. Based on analysis of 583 drydowns, we find storage capacities to vary between 1.3 and 28.4 mm, corresponding to e-folding timescales of 1.8-20.1 days. This makes the urban storage capacity at least five times smaller than all the observed values for natural ecosystems, reflecting an evaporation regime characterized by extreme water limitation.