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.

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.

Clinical and genetic characteristics of Stargardt disease in a large Western China cohort: Report 1.

Stargardt disease 1 (STGD1) is the most prevalent retinal dystrophy caused by pathogenic biallelic ABCA4 variants. Forty-two unrelated patients mostly originating from Western China were recruited. Comprehensive ophthalmological examinations, including visual acuity measurements (subjective function), fundus autofluorescence (retinal imaging), and full-field electroretinography (objective function), were performed. Next-generation sequencing (target/whole exome) and direct sequencing were conducted. Genotype grouping was performed based on the presence of deleterious variants. The median age of onset/age was 10.0 (5-52)/29.5 (12-72) years, and the median visual acuity in the right/left eye was 1.30 (0.15-2.28)/1.30 (0.15-2.28) in the logarithm of the minimum angle of resolution unit. Ten patients (10/38, 27.0%) showed confined macular dysfunction, and 27 (27/37, 73.7%) had generalized retinal dysfunction. Fifty-eight pathogenic/likely pathogenic ABCA4 variants, including 14 novel variants, were identified. Eight patients (8/35, 22.8%) harbored multiple deleterious variants, and 17 (17/35, 48.6%) had a single deleterious variant. Significant associations were revealed between subjective functional, retinal imaging, and objective functional groups, identifying a significant genotype-phenotype association. This study illustrates a large phenotypic/genotypic spectrum in a large well-characterized STGD1 cohort. A distinct genetic background of the Chinese population from the Caucasian population was identified; meanwhile, a genotype-phenotype association was similarly represented.

Oguchi disease caused by a homozygous novel SAG splicing alteration associated with the multiple evanescent white dot syndrome: A 15-month follow-up.

PURPOSE: We report a 15-month follow-up case on a Chinese patient with Oguchi disease associated with the multiple evanescent white dot syndrome (MEWDS). METHODS: The patient's clinical presentation and follow-up visits were documented via decimal best-corrected visual acuity, fundus photography, fundus autofluorescence (FAF) imaging, near-infrared FAF, spectral domain optical coherence tomography, Humphrey's visual fields, microperimetry, and multifocal electroretinography. We also performed whole exome sequencing for screening variation in the patient and her relatives. RESULTS: The patient had typical clinical characteristic of Oguchi disease, including night blindness, the Mizuo-Nakamura phenomenon (a golden yellow discoloration of the fundus that disappears in the prolonged dark adaptation [DA]) and typical full-field electroretinogram changes (nearly undetected b-wave in 0.01 and 0.03 ERGs that can partially recover only after prolonged DA). Aside from Oguchi disease, the patient was also diagnosed with the MEWDS based on clinical detections, including suddenly reduced visual acuity, appeared white dots, blurred ellipsoid zone and disrupted interdigitation zone, enlarged blind spot, and reduced macular sensitivity. A series of investigations revealed that along with the 15-month follow-up after onset, the visual acuity enhanced, the numerous white dots disappeared, and the macular structure returned to normal. Moreover, the novel homozygous splicing alteration c.181 + 1G > A was identified in the SAG gene. CONCLUSIONS: This work is the first long-term case study of a patient with Oguchi disease associated with the MEWDS. The recovery period of symptoms caused by the MEWDS was much longer than that in typical patients with MEWDS. Molecular genetics demonstrate that this is the first case of Oguchi disease caused by splicing alterations in the SAG gene.

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 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 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.

Long-term follow-up of a Chinese patient with KCNV2-retinopathy.

Purpose: To characterize and monitor the clinical and electrophysiological features of a Chinese patient with KCNV2 retinopathy.Methods: A 17-year-old Chinese male with the diagnosis of cone dystrophy with supernormal rod response (CDSRR) was followed-up for 5 years, with full ophthalmological examinations, including decimal best corrected visual acuity (BCVA), fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain optical coherence tomography (SD-OCT), and full-field electroretinogram (ERG). Genetic screening was performed to detect the sequence variations in the retinal dystrophy associated genes in the patient and his parents.Results: The patient demonstrated the characteristic full-field electroretinography (ERG) features of CDSRR, namely a profound enlargement of the dark-adapted ERG b-wave amplitude with increasing flash strength and a broadened a-wave trough; this case also had undetectable light-adapted ERGs. A BCVA of 0.15 was maintained over 5 years in both eyes; while progressive macular atrophy was identified. Molecular genetic analyses revealed two novel disease-causing KCNV2 variants in compound heterozygous state: c.1408 G > C (p.Gly470Arg) and c.1500 C > G (p.Tyr500Ter).Conclusions: This is the first long-term case study of an East Asian patient with molecularly confirmed CDSRR. The progressive atrophy with maintained VA demonstrated in this case will be valuable for increasing the understanding of the natural course of KCNV2 retinopathy and it will help in counselling patients with this disease.

Inkjet Printing of GAP/NC/DNTF based Microscale Booster with High Strength for PyroMEMS.

In order to improve the mechanical strength of micro-booster based on 3,4-dinitrofurazanofuroxan (DNTF), 2,4-toluene diisocyanate (TDI) was introduced into the composite binder of nitrocotton (NC) and glycidyl azide polymer (GAP). A full-liquid explosive ink containing DNTF, binder and solvent was printed layer by layer. By the polymer cross-linking technology, the inkjet printed sample with three-dimensional network structure was obtained. The morphology, crystal form, density, mechanical strength, thermal decomposition and micro scale detonation properties of the printed samples were tested and analyzed. The results show that the printed sample has a smooth surface and a dense internal microstructure, and the thickness of the single layer printing is less than 10 µm. Compared with the raw material DNTF, the thermal decomposition temperature and activation energy of the printed samples do not change significantly, indicating better thermal stability. The addition of curing agent TDI increases the mechanical properties and charge density of the energetic composites. The elastic modulus and hardness are increased by more than 20%. The charge density can attain 1.773 g·cm-3, which can reach 95.5% of the theoretical density. The critical detonation size of the sample can reach 1 mm × 0.01 mm or less and the detonation velocity can achieve 8686 m·s-1, which exhibits excellent micro-scale detonation ability.

Fish oil supplementation and repeated macular hemorrhage without choroidal neovascularization: A case report.

Macular hemorrhage can occur spontaneously and repeatedly without choroidal neovascularization or other known lesions associated with myopia. We report a case of repeated myopic macular hemorrhage following fish oil supplementation. A 32-year-old male was referred with newly acquired paracentral scotoma in the left eye. Serial retinal imaging, including fundus photography, fluorescein angiography, and spectral-domain optical coherence tomography were performed. Fundus photography and fluorescein angiography showed a subtle red-colored lesion nasal to the fovea. Optical coherence tomography showed a dome shaped elevation in the ellipsoid zone and interdigitation zone in the left eye. No known ocular risk factors for macular hemorrhage, such as choroidal neovascularization, lacquer cracks, Fuch's spot or choroid thinning or keratoconus were observed. After 2 months without any treatment, the left eye lesion disappeared. However 2 weeks later, another newly developed red-colored lesion close to the left fovea was observed. At that moment, the detailed medical history revealed that the patient had been regularly taking a high dose of commercially available fish oil supplement beginning one month before the first macular hemorrhage. After discontinuation of the fish oil, the second left hemorrhage resolved gradually over the following 8 weeks. No recurrent hemorrhages have been detected at the 12 months follow-up visits. Our observations suggest that the relative value of nutritional supplementation with high doses of fish oil should be cautioned in patients with repetitive retinal hemorrhage.

Electrophysiological and Structural Changes in Chinese Patients with LHON.

OBJECTIVE: To review retrospectively the electrophysiological and structural changes in 13 Chinese patients with Leber hereditary optic neuropathy (LHON). METHODS: 26 eyes of 13 patients with a genetically confirmed diagnosis of LHON were categorized into two groups according to the duration of the disease: group 1 (duration less than 3 months) and group 2 (duration between 3 months and 18 years). Clinical history, comprehensive visual electrophysiology, optical coherence tomography (OCT), and color fundus photography were performed. RESULTS: Fundoscopy showed optic disc hyperemia in group 1 and optic atrophy in group 2. OCT measures of retinal nerve fiber layer (RNFL) thickness around the optic disc and surrounding macula were normal in group 1 but reduced in group 2 (10 of 10 eyes). The thickness of the retinal ganglion cell layer (GCL) plus inner plexiform layer (IPL) surrounding the macula reduced significantly in group 1 and group 2 compared with a healthy control group. Pattern ERG (PERG) P50 amplitude was normal, but the N95/P50 ratio reduced in most of group 1 (4 of 5 eyes) and in all of group 2 (11 eyes). PERG P50 peak time was abnormally short in group 2. Multifocal electroretinography (mfERG) showed subnormal responses associated with ring 1 (the central area) and ring 2 in group 1 and reductions in rings 1, 2, and 3 in group 2. CONCLUSION: The study highlights differences in retinal structure and function between the acute and chronic stages of LHON in a group of Chinese patients. There is PERG evidence of retinal ganglion cell dysfunction and OCT evidence of GCL + IPL thinning in both groups, but there is additional peripapillary RNFL loss in the chronic stage, associated with more severe RGC dysfunction. There is multifocal ERG evidence of localized macular dysfunction in both acute and chronic groups. The study highlights the importance of comprehensive electrophysiological and structural assessments of the retina in LHON and is pertinent to studies that aim to monitor disease progression or the effects of future therapeutic interventions.

Identification of 13 novel USH2A mutations in Chinese retinitis pigmentosa and Usher syndrome patients by targeted next-generation sequencing.

BACKGROUND: The USH2A gene encodes usherin, a basement membrane protein that is involved in the development and homeostasis of the inner ear and retina. Mutations in USH2A are linked to Usher syndrome type II (USH II) and non-syndromic retinitis pigmentosa (RP). Molecular diagnosis can provide insight into the pathogenesis of these diseases, facilitate clinical diagnosis, and identify individuals who can most benefit from gene or cell replacement therapy. Here, we report 21 pathogenic mutations in the USH2A gene identified in 11 Chinese families by using the targeted next-generation sequencing (NGS) technology. METHODS: In all, 11 unrelated Chinese families were enrolled, and NGS was performed to identify mutations in the USH2A gene. Variant analysis, Sanger validation, and segregation tests were utilized to validate the disease-causing mutations in these families. RESULTS: We identified 21 pathogenic mutations, of which 13, including 5 associated with non-syndromic RP and 8 with USH II, have not been previously reported. The novel variants segregated with disease phenotype in the affected families and were absent from the control subjects. In general, visual impairment and retinopathy were consistent between the USH II and non-syndromic RP patients with USH2A mutations. CONCLUSIONS: These findings provide a basis for investigating genotype-phenotype relationships in Chinese USH II and RP patients and for clarifying the pathophysiology and molecular mechanisms of the diseases associated with USH2A mutations.

Inkjet printing of energetic composites with high density.

To explore a new manufacturing method in preparing energetic composites, an inkjet printing device possessing the ability of high precision and flexibility was utilized to deposit six 3,4-dinitrofurazanofuroxan (DNTF) and hexogen (RDX) based explosive inks. The printed quality, inner structure, printed density and crystal morphology of energetic composites were tested, as well as their thermal decomposition properties and detonation properties. The results indicate that inkjet printing provides a good formation uniformity for explosive inks. Interestingly, all energetic composites exhibit excellent printed density with all values higher than 90% theoretical maximum density (TMD). Meanwhile, the composite DNTF/RDX/EC/GAP (54/36/5/5) performs best, reaching 96.88% TMD, which has reached a new height in the three-dimensional printing of energetic composites. Further study manifests that there is no appearance of new material, and the stacking manner of rodlike structures in multilayer manufacturing is the key to achieving such an amazing result. The particles in the energetic composites are spherical with the size ranging from 500 nm to 2 µm and connect with each other closely in the matrix of binders. Moreover, the energetic composites that were directly deposited into wedge channels display a good capability in steadily detonating above the size of 1 × 0.32 mm.