Varied clinical presentations of RP1L1 variants in Chinese patients: a study of occult macular dystrophy and vitelliform macular dystrophy.

BACKGROUND: Occult Macular Dystrophy (OMD), primarily caused by retinitis pigmentosa 1-like 1 (RP1L1) variants, is a complex retinal disease characterised by progressive vision loss and a normal fundus appearance. This study aims to investigate the diverse phenotypic expressions and genotypic correlations of OMD in Chinese patients, including a rare case of Vitelliform Macular Dystrophy (VMD) associated with RP1L1. METHODS: We analysed seven OMD patients and one VMD patient, all with heterozygous pathogenic RP1L1 variants. Clinical assessments included Best Corrected Visual Acuity (BCVA), visual field testing, Spectral Domain Optical Coherence Tomography (SD-OCT), multifocal Electroretinograms (mfERGs), and microperimetry. Next-generation sequencing was utilised for genetic analysis. RESULTS: The OMD patients displayed a range of phenotypic variability. Most (5 out of 7) had the RP1L1 variant c.133 C > T; p.R45W, associated with central vision loss and specific patterns in SD-OCT and mfERG. Two patients exhibited different RP1L1 variants (c.3599G > T; p.G1200V and c.2880G > C; p.W960C), presenting milder phenotypes. SD-OCT revealed photoreceptor layer changes, with most patients showing decreased mfERG responses in the central rings. Interestingly, a unique case of VMD linked to the RP1L1 variant was observed, distinct from traditional OMD presentations. CONCLUSIONS: This study highlights the phenotypic diversity within OMD and the broader spectrum of RP1L1-associated macular dystrophies, including a novel association with VMD. The findings emphasise the complexity of RP1L1 variants in determining clinical manifestations, underscoring the need for comprehensive genetic and clinical evaluations in macular dystrophies.

Intrathecal morphine delivery at prepontine cistern to control refractory cancer-related pain: a case report of extensive metastatic and refractory cancer pain.

BACKGROUND: Extensive metastatic and refractory cancer pain is common, and exhibits a dissatisfactory response to the conventional intrathecal infusion of opioid analgesics. CASE PRESENTATION: The present study reports a case of an extensive metastatic esophageal cancer patient with severe intractable pain, who underwent translumbar subarachnoid puncture with intrathecal catheterization to the prepontine cistern. After continuous infusion of low-dose morphine, the pain was well-controlled with a decrease in the numeric rating scale (NRS) of pain score from 9 to 0, and the few adverse reactions to the treatment disappeared at a low dose of morphine. CONCLUSIONS: The patient achieved a good quality of life during the one-month follow-up period.

Impact of delay extubation on the reintubation rate in patients after cervical spine surgery: a retrospective cohort study.

BACKGROUND: The incidence of cervical airway obstruction after cervical spine surgery (CSS) ranges from 1.2 to 14%, and some require reintubation. If not addressed promptly, the consequences can be fatal. This study investigated delayed extubation's effect on patients' reintubation rate after cervical spine surgery. METHODS: We performed a retrospective case-control analysis of cervical spine surgery from our ICU from January 2021 to October 2022. Demographic and preoperative characteristics, intraoperative data, and postoperative clinical outcomes were collected for all 94 patients. Univariable analysis and multivariable logistic regression were used to analyze postoperative unsuccessful extubation risk factors following cervical spine surgery. RESULTS: The patients in the early extubation (n = 73) and delayed extubation (n = 21) groups had similar demographic characteristics. No significant differences were found in the reintubation rate (0 vs. 6.8%, p = 0.584). However, the delayed extubation group had significantly more patients with 4 and more cervical fusion segments (42.9 vs. 15.1%, p = 0.013),more patients with an operative time greater than 4 h (33.3 vs. 6.8%, p = 0.004)and all patients involved C2-4 (78 vs. 100%, p = 0.019).Also, patients in the delayed extubation group had a longer duration of ICU stay (152.9 ± 197.1 h vs. 27.2 ± 45.4 h, p < 0.001) and longer duration of hospital stay (15.2 ± 6.9 days vs. 11.6 ± 4.1 days, p = 0.003). Univariate and multivariate analysis identified the presences of cervical spondylotic myelopathy (CSM) (OR 0.02, 95% CI 0-0.39, p = 0.009) and respiratory diseases (OR: 23.2, 95% CI 2.35-229.51, p = 0.007) as unfavorable prognostic factor for reintubation. CONCLUSIONS: Our analysis of patients with cervical spondylosis who received CSS indicated that delayed extubation was associated with the presence of respiratory diseases and CSM, longer operative time, more cervical fusion segments, and longer duration of ICU and hospital stays.

SaAlign: Multiple DNA/RNA sequence alignment and phylogenetic tree construction tool for ultra-large datasets and ultra-long sequences based on suffix array.

Multiple DNA/RNA sequence alignment is an important fundamental tool in bioinformatics, especially for phylogenetic tree construction. With DNA-sequencing improvements, the amount of bioinformatics data is constantly increasing, and various tools need to be iterated constantly. Mitochondrial genome analyses of multiple individuals and species require bioinformatics software; therefore, their performances need to be optimized. To improve the alignment of ultra-large datasets and ultra-long sequences, we optimized a dynamic programming algorithm using longest common substring methods. Ultra-large test DNA datasets, containing sequences of different lengths, some over 300 kb (kilobase), revealed that the Multiple DNA/RNA Sequence Alignment Tool Based on Suffix Tree (SaAlign) saved time and computational space. It outperformed the existing technical tools, including MAFFT and HAlign-II. For mitochondrial genome datasets having limited numbers of sequences, MAFFT performed the required tasks, but it could not handle ultra-large mitochondrial genome datasets for core dump error. We implement a multiple DNA/RNA sequence alignment tool based on Center Star strategy and use suffix array algorithm to optimize the spatial and time efficiency. Nowadays, whole-genome research and NGS technology are becoming more popular, and it is necessary to save computational resources for laboratories. That software is of great significance in these aspects, especially in the study of the whole-mitochondrial genome of plants.

Ocular Characteristics of Patients with Leber Congenital Amaurosis 6 Caused by Pathogenic RPGRIP1 Gene Variation in a Chinese Cohort.

PURPOSE: To delineate the clinical and genetic characteristics of Chinese patients with RPGRIP1-associated Leber congenital amaurosis 6 (LCA6). METHODS: After screening 352 unrelated families with clinically diagnosed RP, five LCA6 patients with RPGRIP1 variations from unrelated Chinese families were identified. Full ophthalmology examinations, including decimal best-corrected visual acuity (BCVA), fundus photography, fundus autofluorescence imaging, spectral-domain optical coherence tomography (SD-OCT), full-field electroretinography (ffERG), multifocal electroretinography (mfERG), perimetry, and flash visual evoked potential (FVEP), were performed. Target next-generation sequencing (NGS) and Sanger sequencing were performed for the five patients to identify and to validate candidate disease-causing variants. RESULTS: Five patients were molecularly diagnosed as the LCA6 associated with RPGRIP1 variation, with typical clinical characteristics including congenital night blindness, nystagmus, and visual defect, at an early age. Interestingly, LCA6 exhibited extensive clinical heterogeneity and the changes in the morphology and function were not completely consistent in the five LCA6 patients. Case 1 showed extensive inferior-nasal retinal atrophy with a corresponding area of hypofluorescence in fundus autofluorescence, and the fundus photograph was nearly normal in cases 2 and 3. The ERG results displayed a moderately reduced rod-system response in cases 1 and 2 and a significant reduced rod-system response in case 3. Both case 4 and case 5 showed mottled pigmentation in fundi and an unrecordable rod and cone-system response in ERG. Moreover, we identified eight compound variants and one homozygous variant in the five patients with RPGRIP1. CONCLUSIONS: This is the largest report focused on the clinical electrophysiological features of patients with associated LCA6 caused by the variation in the RPGRIP1 gene in the Chinese population with an enriched phenotypic and genotypic background of LCA6 to improve future gene therapies.

Spatial-Temporal Footprints Assessment and Driving Mechanism of China Household Diet Based on CHNS.

Food consumption is closely associated with resource consumption and environmental sustainability. An unreasonable dietary pattern would cause great pressure or damage to resources and the environment. It is particularly important to reduce the negative impact of household food consumption on resources and the environment while simultaneously ensuring people's nutrient intake and health. This study applied the China Health and Nutrition Survey (CHNS) database to quantitatively study the spatial-temporal analysis of multiple footprints of household food consumption at multiple scales and explored the driving mechanism of the multiple footprints. The results showed that, except land footprint (LF), the other four types of footprints all decreased at varying degrees; the water footprint (WF), carbon footprint (CF), nitrogen footprint (NF) and energy footprint (EF) decreased by 18.24%, 17.82%, 12.03% and 20.36%, respectively, from 2000 to 2011; multiple footprints of food consumption of household in Guizhou was the highest among the 12 provinces involved in the study; this shows that resource consumption (water, energy and land resource) and environmental influences (CO2 emissions and nitrogen emissions) brought by food consumption of per household in Guizhou are much greater than in other provinces, which has a negative influence on sustainable development; by analyzing the driving factors of multiple footprints, it is shown that nutrient intake, household attributes, educational level and health conditions were significantly correlated to multiple footprints. Among them, nutrient intake has greater impact on the multiple footprints of Chinese household food consumption. By comparing multiple footprints of different dietary patterns, it was found that the current Chinese dietary pattern would cause excessive resource consumption, which would bring more pressure on resources and the environment. Adjusting household living habits would possibly reverse the unsustainable situation, such as reducing the consumption of animal-derived foods and adjusting the dietary pattern of households with a higher educational level and income status. Chinese Dietary Guidelines 2016 has better sustainability; the promotion of this dietary pattern across the country would help China to relieve the pressure on resources and environment from the consumer side, promoting the realization of sustainable development.

Ocular Characteristics of Patients With Bardet-Biedl Syndrome Caused by Pathogenic BBS Gene Variation in a Chinese Cohort.

Bardet-Biedl syndrome (BBS; OMIM 209900) is a rare genetic disease causing damage to multiple organs and affecting patients' quality of life in late adolescence or early adulthood. In this study, the ocular characteristics including morphology and function, were analyzed in 12 BBS patients from 10 Chinese families by molecular diagnostics. A total of five known and twelve novel variants in four BBS genes (BBS2, 58.33%; BBS4, 8.33%; BBS7, 16.67%; and BBS9, 16.67%) were identified in 10 Chinese families with BBS. All patients had typical phenotypes of retinitis pigmentosa with unrecordable or severely damaged cone and rod responses on full-field flash electroretinography (ffERG). Most of the patients showed unremarkable reactions in pattern visual evoked potential (PVEP) and multifocal electroretinography (mfERG), while their flash visual evoked potentials (FVEP) indicated display residual visual function. Changes in the fundus morphology, including color fundus photography and autofluorescence (AF) imaging, were heterogeneous and not consistent with the patients' functional tests. Overall, our study expands the variation spectrum of the BBS gene, showing that the ocular characteristics of BBS patients are clinically highly heterogeneous, and demonstrates the usefulness of a combination of the ffERG and FVEP assessments of visual function in the advanced stage of retinopathy in BBS.

Ocular abnormalities in a large patient cohort with retinitis pigmentosa in Western China.

BACKGROUND: To report the prevalence of ocular abnormalities and investigate visual acuity in a large cohort of retinitis pigmentosa (RP) patients in Western China. METHODS: The medical records and ophthalmic examination reports of 2127 eyes of 1065 RP patients at one eye hospital were retrospectively reviewed to determined the prevalence of ocular abnormalities and the relationship between best corrected visual acuity (BCVA) and macular abnormalities. RESULTS: Nyctalopia (58.2%) and blurred vision (27.1%) were the leading reasons for RP patients to request an ophthalmic examination. BCVA measurements in the better eyes at first clinical presentation showed that 304 patients (28.5%) were categorised as blind and 220 patients (20.7%) as low vision. The most common ocular abnormalities were macular abnormalities (59.7%) and cataracts (43.1%). The macular abnormalities included epiretinal membranes (51.1%), cystoid macular edema (18.4%), vitreomacular traction syndrome (2.4%), macular holes (2.3%) and choroidal neovascular membranes (0.05%). Glaucoma was found in 35 eyes (1.6%). The proportions of epiretinal membranes (p = 0.001) and macular holes (p = 0.008) increased significantly with age. Cystoid macular edema was significantly associated with poorer visual acuity in RP patients with clear lens (p = 0.002). CONCLUSION: Cataracts and macular abnormalities are common in RP patients. Of the macular abnormalities, cystoid macular edema may have a negative effect on BCVA in RP patients with clear lens. Therefore, optical coherence tomography screening in RP patients is highly recommended for early detection and treatment of maculopathy.