[Effect of phacoemulsification on the Berger space].

Objective: To investigate the effect of phacoemulsification on the Berger space (BS). Methods: A prospective cohort study. Patients with cataract who underwent phacoemulsification and intraocular lens implantation in the Department of Ophthalmology, Affiliated Hospital of Nantong University from May 2021 to October 2021 were enrolled. The BS was observed by slit-lamp microscopy and anterior segment optical coherence tomography (AS-OCT) before and 1 month after operation. Intraoperative optical coherence tomography with a 25G optical fiber was performed to observe the BS. The number of eyes with the BS and materials in the BS (MIB) detected perioperatively was counted, and the width of the BS was measured. Statistical analysis was carried out by the Chi-square test, generalized estimating equations, Mann-Whitney U test and binary logistic regression analysis. Results: A total of 119 patients (119 eyes) were included [44 males, 75 females; mean age, (65±12) years]. Preoperatively, the BS was identified in only 4 eyes (3.4%), and no MIB was found. Intraoperatively, the BS was identified in 47 eyes (39.5%), and the MIB was observed in 20 eyes (16.8%). At one month postoperatively, the BS was identified in 33 eyes (27.7%), of which 16 eyes (13.4%) still had MIB. There were significant differences in the detection rates of the BS and MIB between intraoperative and preoperative groups (both P<0.001). The difference in the detection rate of the BS postoperatively compared to intraoperatively was statistically significant (P=0.001), while the difference in the detection rate of MIB was not statistically significant (P>0.05). The intraoperative and postoperative width of the BS [M (Q1, Q3)] was 160.3 (61.6, 273.1) µm and 106.8 (0, 259.4) µm, respectively, and the difference was statistically significant (Z=-2.28, P=0.023). In addition, the detection rate of the BS and MIB in patients with a high risk of zonular fiber weakness [60.7% (17/28) and 42.9% (12/28)] was significantly higher than that in patients without this risk factor [33.0% (30/91) and 8.8% (8/91)] (χ²=6.90, P=0.009; P<0.001). In the multivariable model, weakness of zonular fibers (OR=0.214, 95%CI: 0.081 to 0.561) and higher cumulative dissipated energy (OR=1.255, 95%CI: 1.047 to 1.504) were the main risk factors for structural changes of the BS intraoperatively. Conclusion: Phacoemulsification can damage the normal anatomical structure of the BS, resulting in intraoperative entrance of fluid and particulates to the BS.

Aberrant accumulation of ErbB4 in progressive supranuclear palsy.

AIMS: The human epidermal growth factor receptor family consists of four members that belong to the ErbB lineage of proteins (ErbB1-4). Neuregulin-1 (NRG1)/ErbB signalling regulates brain development and function. Abnormalities in this signalling have been implicated in the aetiology or development of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. So, we aimed at investigating whether the expression of NRG1 or ErbB proteins are altered in progressive supranuclear palsy (PSP). METHODS: The brains of 10 PSP and six control patients were investigated by immunohistochemical analysis. RESULTS: Whereas C-terminal ErbB4 immunoreacitivity was partially but distinctly present in the cytoplasm and/or in the nucleus of neurons in control patients, it was rarely observed in the neuronal nuclei in PSP patients. In contrast, neurofibrillary tangles, coiled bodies and threads were robustly immunoreactive for C-terminal ErbB4 in PSP. Double immunofluorescence for C-terminal ErbB4 and phospho-tau revealed co-localization of these proteins within neuronal and glial inclusions. To the contrary, there was no difference in the subcellular localization of NRG1, ErbB1, ErbB2, and N-terminal ErbB4 between control and PSP patients. These proteins were localized in the cytoplasm of neurons. CONCLUSIONS: Our present results suggest that NRG1/ErbB4 signalling could be an important event in the pathogenesis of PSP.

TDP-43 pathology in multiple system atrophy: colocalization of TDP-43 and α-synuclein in glial cytoplasmic inclusions.

AIMS: This study aimed to assess clinicopathologic features of transactive response DNA-binding protein of 43 kDa (TDP-43) pathology and its risk factors in multiple system atrophy (MSA). METHODS: Paraffin-embedded sections of the amygdala and basal forebrain from 186 autopsy-confirmed MSA cases were screened with immunohistochemistry for phospho-TDP-43. In cases having TDP-43 pathology, additional brain regions were assessed. Immunohistochemical and immunofluorescence double-staining and immunogold electron microscopy (IEM) were performed to evaluate colocalization of TDP-43 and α-synuclein. Genetic risk factors for TDP-43 pathology were also analysed. RESULTS: Immunohistochemistry showed various morphologies of TDP-43 pathology in 13 cases (7%), such as subpial astrocytic inclusions, neuronal inclusions, dystrophic neurites, perivascular inclusions and glial cytoplasmic inclusions (GCIs). Multivariable logistic regression models revealed that only advanced age, but not concurrent Alzheimer's disease, argyrophilic grain disease or hippocampal sclerosis, was an independent risk factor for TDP-43 pathology in MSA (OR: 1.11, 95% CI: 1.04-1.19, P = 0.002). TDP-43 pathology was restricted to the amygdala in eight cases and extended to the hippocampus in two cases. The remaining three cases had widespread TDP-43 pathology. Immunohistochemical and immunofluorescence double-staining and IEM revealed colocalization of α-synuclein and TDP-43 in GCIs with granule-coated filaments. Pilot genetic studies failed to show associations between risk variants of TMEM106B or GRN and TDP-43 pathology. CONCLUSIONS: TDP-43 pathology is rare in MSA and occurs mainly in the medial temporal lobe. Advanced age is a risk factor for TDP-43 pathology in MSA. Colocalization of TDP-43 and α-synuclein in GCIs suggests possible direct interaction between the two molecules.

[The status quo and analysis of quality control of cancer chemotherapy in 76 hospitals in Beijing].

Objective: Investigated the status quo of quality control of cancer chemotherapy in hospitals in Beijing to discover the main problems and provide the improvement measures. Methods: One medical record of cancer chemotherapy was taken every month for examination of quality control, and a total of 10 medical records in each hospital were examined. A total of 756 medical records from 76 hospitals were examined. Results: The results of analysis showed that the overall standardization and quality control of cancer chemotherapy was positively correlated with the grade of hospital. Only 36.8% of the hospitals were equipped with Pharmacy Intravenous Admixture Services (PIVAS). In terms of quality control of chemotherapy and medicine, the department of oncology had better performance than other departments (P<0.01). The scores of quality control of chemotherapy and medicine in the hospitals with clinical specialist pharmacists were 50.6 and 14.5, significantly higher than 47.2 and 12.7 of those without clinical specialist pharmacists (P<0.05). Conclusion: We should focus on the quality control of cancer chemotherapy in secondary hospitals, reinforce the training of oncology specialists, establish the admission system of oncologists, enhance the training of oncology clinical pharmacists and promote the standardization of cancer chemotherapy.

Multidie LED combined with homogenizing optics to improve frequency response and intensity for FLIM applications.

Application of light-emitting diodes (LEDs) in frequency-domain fluorescence lifetime imaging microscopy (FLIM) has been limited by the trade-off between modulation frequency and illumination intensity of LEDs, which affects the signal-to-noise ratio in fluorescence lifetime measurements. To increase modulation frequency without sacrificing output power of LEDs, we propose to use LEDs with multiple dice connected in series. The LED capacitance was reduced with series connection; therefore, the frequency response of multidie LED was significantly increased. LEDs in visible light, including blue, green, amber and red, were all applicable in FLIM. We also present a homogenizing optics design, so that multidie LEDs produced uniform illumination on the same focal spot. When the homogenizing optics was combined with multicolour emitters, it provides multiple colour selection in a compact and convenient design.

Total body composition estimated by standing-posture 8-electrode bioelectrical impedance analysis in male wrestlers.

Standing-posture 8-electrode bioelectrical impedance analysis is a fast and practical method for evaluating body composition in clinical settings, which can be used to estimate percentage body fat (BF%) and skeletal muscle mass in a subject's total body and body segments. In this study, dual-energy X-ray absorptiometry (DXA) was used as a reference method for validating the standing 8-electrode bioelectrical impedance analysis device BC-418 (BIA8, Tanita Corp., Tokyo, Japan). Forty-eight Taiwanese male wrestlers aged from 17.9 to 22.3 years volunteered to participate in this study. The lean soft tissue (LST) and BF% in the total body and body segments were measured in each subject by the BIA8 and DXA. The correlation coefficients between total body, arm, leg segments impedance index (BI, ht2/Z) and lean soft tissue mass measured from DXA were r = 0.902, 0.453, 0.885, respectively (p < 0.01). In addition, the total body and segmental LST estimated by the BIA8 were highly correlated with the DXA data (r = 0.936, 0.466, 0.886, p < 0.01). The estimation of total body and segmental BF% measured by BIA8 and DXA also showed a significant correlation (r > 0.820, p < 0.01). The estimated LST and BF% from BIA8 in the total body and body segments were highly correlated with the DXA results, which indicated that the standing-posture 8-electrode bioelectrical impedance analysis may be used to derive reference measures of LST and BF% in Taiwanese male wrestlers.

The use of procalcitonin in the diagnosis of bone and joint infection: a systemic review and meta-analysis.

Only a few studies have investigated the use of PCT in the diagnosis of bone and joint infection, and these studies have had relatively small sample sizes. We performed a systematic review and meta-analysis of the diagnostic performance of serum procalcitonin (PCT) in the identification of osteomyelitis and septic arthritis in patients who present with fever and orthopedic symptoms. EMBASE, MEDLINE, and Cochrane databases and the reference lists of relevant articles were searched, with no language restrictions, through February 2012. All original studies that reported the use of serum PCT alone or in comparison with other biomarkers for diagnosis of osteomyelitis and septic arthritis were included. Seven studies qualified for inclusion. These studies enrolled a total of 583 patients with suspected bone or joint infection, 131 of whom had confirmed osteomyelitis or septic arthritis. Analysis of the PCT data indicated a bivariate pooled sensitivity of 0.67 (95 % CI: 0.37-0.88), specificity of 0.90 (95 % CI: 0.78-0.96), a positive likelihood ratio (LR+) of 6.48 (95 % CI: 2.28-14.6), and a negative likelihood ratio (LR-) of 0.37 (95 % CI: 0.16-0.84). Use of a lower PCT cut-off value (0.2-0.3 ng/mL) improved the LR + to 6.66 and the LR- to 0.15. Analysis of the three studies that also measured serum C-reactive protein (CRP) indicated that CRP had an LR + of 1.39 (95 % CI: 1.17-1.65) and an LR- of 0.40 (95 % CI: 0.12-1.36). Our results indicate that PCT may be more suitable as an aid for rule-in diagnosis rather than for exclusion of septic arthritis or osteomyelitis and that use of a lower cut-off value for serum PCT may improve its diagnostic performance.

Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein.

Neurofibrillary tangles (NFT) composed of the microtubule-associated protein tau are prominent in Alzheimer disease (AD), Pick disease, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Mutations in the gene (Mtapt) encoding tau protein cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), thereby proving that tau dysfunction can directly result in neurodegeneration. Expression of human tau containing the most common FTDP-17 mutation (P301L) results in motor and behavioural deficits in transgenic mice, with age- and gene-dose-dependent development of NFT. This phenotype occurred as early as 6.5 months in hemizygous and 4.5 months in homozygous animals. NFT and Pick-body-like neuronal lesions occurred in the amygdala, septal nuclei, pre-optic nuclei, hypothalamus, midbrain, pons, medulla, deep cerebellar nuclei and spinal cord, with tau-immunoreactive pre-tangles in the cortex, hippocampus and basal ganglia. Areas with the most NFT had reactive gliosis. Spinal cord had axonal spheroids, anterior horn cell loss and axonal degeneration in anterior spinal roots. We also saw peripheral neuropathy and skeletal muscle with neurogenic atrophy. Brain and spinal cord contained insoluble tau that co-migrated with insoluble tau from AD and FTDP-17 brains. The phenotype of mice expressing P301L mutant tau mimics features of human tauopathies and provides a model for investigating the pathogenesis of diseases with NFT.

High risk of cross-reactivity between vancomycin and sequential teicoplanin therapy.

WHAT IS KNOWN AND OBJECTIVE: Teicoplanin and vancomycin show similar clinical and bacteriological efficacy in clinical trials. Teicoplanin has been reported to have a lower adverse drug reaction (ADR) rate than vancomycin. Cross-reactivity between these two glycopeptides is controversial. Our aim was to study the cross-reactivity between teicoplanin and vancomycin through an assessment of all the reported ADRs of these drugs in our University hospital. METHODS: Over a period of 2 years, 170 cases of vancomycin therapy, which were closely monitored by doctors and clinical pharmacists, were used to analyse ADRs. Teicoplanin therapy was used as an alternative in cases of vancomycin intolerance. When an ADR related to vancomycin or teicoplanin was suspected, specialists were consulted to confirm if these were true ADR and to determine whether the implicated drug should be stopped. All ADRs for the two glycopeptides were assessed for causality using the Naranjo probability scale. RESULTS AND DISCUSSION: Thirty-eight of 170 patients (22·4%) treated with vancomycin developed ADRs. Twenty-four patients were switched to teicoplanin. However, 14 of those 24 patients (58·3%) developed ADRs. The time of onset of ADRs involving vancomycin was 12·7 ± 10·9 days (range, 1-46 days). The time of onset of sequential teicoplanin-induced ADRs was 11·7 ± 4·7 days (range, 2-20 days). Of the 14 patients with ADRs related to sequential teicoplanin therapy, six showed cross-reactivity between vancomycin and teicoplanin. The incidence of vancomycin-induced neutropenia was 4·7% (8/170), whereas the incidence of teicoplanin-induced neutropenia subsequent to vancomycin intolerance was as high as 33·3% (8/24). Furthermore, 71·4% (10/14) of the teicoplanin-induced ADRs were associated with haematological abnormalities such as neutropenia, thrombocytopenia or leucopenia. WHAT IS NEW AND CONCLUSION: Teicoplanin, used as an alternative in cases of vancomycin intolerance, was associated with a high incidence of ADRs and haematological reactions, most notably neutropenia. This high rate of ADRs suggests cross-reactivity between the two glycopeptides.

[Analysis of 2 diagnostic criteria of echocardiography for coronary artery aneurysm in Kawasaki disease].

Objective: To analyze the difference between Z score and previous criteria in the diagnosis characteristics of coronary artery aneurysm (CAA) in Kawasaki disease, and to investigate the clinical distribution of Kawasaki disease CAA in the Z score group. Methods: This study retrospectively analyzed the clinical and echocardiographic data of 2 419 children with Kawasaki disease in Shenzhen Children's Hospital from January 2009 to December 2019. The traditional criteria and Z score criteria were used to diagnose CAA, and the differences of diagnostic efficiency between the 2 diagnostic methods were analyzed. The clinical distribution characteristics of CAA in children with Kawasaki disease were analyzed by grouping their sex, clinical classification (complete Kawasaki disease, incomplete Kawasaki disease) the sensitivity to intravenous immunoglobulin (IVIG) (IVIG-sensitive Kawasaki disease,IVIG-unresponsive Kawasaki disease). And the course of the disease (≤6 weeks, >6-8 weeks, >8 weeks to 6 months) etc. The χ² test or Kruskal-Wallis test was used for comparison between the groups, and the Kappa test was used for consistency evaluation. Results: Among the 2 419 children with Kawasaki disease, 1 558 were males and 861 were females. The age of onset was 1.8 (1.0, 3.2) years. The rate of CAA by Z score criteria was higher than that by traditional method (21.9% (529/2 419) vs. 13.9% (336/2 419), χ2=1 074.94, P<0.001). Compared to the traditional method, the Z score criteria found higher rate of CAA in male patients, patients with incomplete Kawasaki disease, and IVIG-unresponsive patients (25.2% (392/1 558) vs. 16.0% (249/1 558), (32.7% (166/507) vs. 19.5% (99/507), 30.5% (95/312) vs. 24.0% (75/312), χ2=694.05, 216.19, 184.37, all P<0.001). The Z score criteria was consistent with the traditional method in diagnosing CAA (κ=0.642,P<0.001). Moreover, in the Z score criteria, the rate of CAA in males (25.2%, 392/1 558) was higher than that in females (15.9%, 137/861), higher in incomplete Kawasaki cases (32.7%, 166/507) than that in complete Kawasaki case (19.0%, 363/1 912), and higher in IVIG-unresponsive cases (30.4%, 95/312) than that in IVIG-sensitive cases (20.6%, 434/2 107), with statistically significant differences (χ2=27.76, 44.38, 15.43, all P<0.001). Coronary Z score of course ≤ 6 weeks was greater than that of course between>6-8 weeks and >8 weeks to 6 months (1.3 (0.7, 2.3) vs. 0.7 (0.3, 1.4), 0.7 (0.3, 1.3), Z=20.65, 13.70, both P<0.001). Conclusions: The rate of CAA in Kawasaki disease by Z score criteria is higher than that by traditional method. In the Z score group, most CAA occur within 6 weeks of the course of the disease, and the rate of CAA in male, incomplete Kawasaki disease, and IVIG-unresponsive is higher.

Teicoplanin-induced hypersensitivity syndrome with a preceding vancomycin-induced neutropenia: a case report and literature review.

Hypersensitivity syndrome associated with teicoplanin has rarely been reported. We report a case with a preceding episode of vancomyin-related neutropenia. A 47-year-old female with cervical spine infection was treated with vancomycin. Neutropenia occurred after 17 days of vancomycin therapy. Vancomycin was changed to teicoplanin, and the neutropenia resolved 4 days later. After 11 days of teicoplanin therapy, a new episode of hypersensitivity syndrome manifested as fever, bilateral neck lymphadenopathy, mild wheezing, hepatitis and increased CRP occurred. Neutropenia and thrombocytopenia developed 3 days later. The patient's symptoms settled over 1 week following withdrawal of teicoplanin. Naranjo's ADR algorithm categorized the neutropenia associated with vancomycin and the hypersensitivity syndrome associated with teicoplanin as 'probable'.

Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP.

JNPL3 transgenic mice expressing a mutant tau protein, which develop neurofibrillary tangles and progressive motor disturbance, were crossed with Tg2576 transgenic mice expressing mutant beta-amyloid precursor protein (APP), thus modulating the APP-Abeta (beta-amyloid peptide) environment. The resulting double mutant (tau/APP) progeny and the Tg2576 parental strain developed Abeta deposits at the same age; however, relative to JNPL3 mice, the double mutants exhibited neurofibrillary tangle pathology that was substantially enhanced in the limbic system and olfactory cortex. These results indicate that either APP or Abeta influences the formation of neurofibrillary tangles. The interaction between Abeta and tau pathologies in these mice supports the hypothesis that a similar interaction occurs in Alzheimer's disease.

Ribonucleoprotein organization of eukaryotic RNA. XXXI. Structure of the U1 small nuclear ribonucleoprotein.

A small nuclear ribonucleoprotein, U1 snRNP, has been implicated in mRNA processing. In this investigation sites of protein binding on U1 RNA were mapped by nuclease protection and RNA sequencing. Partially purified human U1 snRNP was sequentially digested with Escherichia coli RNAase III and S1 nuclease. The resistant ribonucleoprotein fragments were deproteinized, preparatively hybridized to the U1 RNA--complementary DNA strand of a human U1 gene cloned in bacteriophage M13, and displayed by electrophoresis. The nuclease-resistant U1 RNA fragments were between 23 and 63 nucleotides in length. Most of these fragments were not obtained when protein-free U1 RNA was similarly digested, whereas others were obtained in low yield from U1 RNA and much higher yield from U1 snRNP. RNA sequencing of the fragments revealed that the protein-protected sites in U1 snRNP correspond to base-paired stems I and II, loop a, and portions of stems III and IV (secondary structure nomenclature of Branlant et al., 1981). Single, "bulged" pyrimidines are present within the protein-covered helical regions of stems I and III. Most interestingly, the single-stranded 5' end of U1 RNA, implicated in mRNA splicing, was also highly protected by protein. These results demonstrate that the great majority of U1 RNA is covered by protein in U1 snRNP. The association of protein with the 5' end of U1 RNA is in agreement with recent evidence that snRNP proteins potentiate the binding of this region of U1 RNA with pre-mRNA splice sites.

Co-ordinate control of gene expression. Muscle-specific 7 S RNA contains sequences homologous to 3'-untranslated regions of myosin genes and repetitive DNA.

We have cloned and sequenced a complementary DNA copy (pSS48) of a novel muscle-specific, low molecular weight RNA, 7 S RNA, isolated from embryonic chick cardiac muscle cells. The hybridization pattern of plasmid pSS48 DNA to chick genomic DNA suggests that 7 S RNA is derived from the repetitive chick DNA with a repetition frequency of about 300 copies per haploid genome. Under low stringency, pSS48 DNA also hybridizes with high specificity to the single copy gene for chick myosin light chain (MLC) and to myosin heavy chain (MHC), and possibly to other co-ordinately expressed genes for chick muscle proteins. The sequence analysis of recombinant plasmids pSS48, pML10 and pMHC8, for 7 S RNA, MLC mRNA and MHC RNA, respectively, indicated that short nucleotide stretches homologous to 7 S RNA reside in the 3' untranslated regions of the respective genes. The 7 S RNA sequence appears to be highly specific for the chick muscle tissue, since RNA and DNA from several sources did not hybridize to pSS48 DNA. Furthermore, the 7 S RNA-like sequence(s) appears in chick blastodermal cells preferentially earlier than the onset of transcription of genes for major muscle proteins. These results, taken together, suggest a possible function for 7 S RNA in expression of muscle-specific genes during chick development.

The genotype and epigenotype synergize to diversify the spatial pattern of expression of the imprinted H19 gene.

Little is known of how the genetic background effects the phenomenon of genomic imprinting. The H19 gene belongs to a cluster of imprinted genes on human chromosome 11. Here we show that the alternative splicing of a human H19 transcript is genotype-specific. Moreover, this variant transcript, which lacks exon 4, is either not found at all, is widely expressed or is confined to extra-villous cytotrophoblasts in first trimester placenta, depending on a combination of the genotype and the sex of the transmitting parent.

A qualitative and quantitative study of grumose degeneration in progressive supranuclear palsy.

Grumose degeneration (GD) of the dentate nucleus is a common feature in progressive supranuclear palsy (PSP), but its pathogenesis has not been well studied, and its clinical significance remains unknown. This report describes a quantitative study of GD in 9 cases of PSP using image analysis with single- and double-immunolabeling, as well as histochemical stains for myelin and axons. GD was associated with demyelination, axonal loss, glial tau pathology, and microgliosis in regions juxtaposed to the dentate nucleus (DN). Specifically, demyelination and microgliosis were prominent in the superior cerebellar peduncle (SCP), dentate hilus, and cerebellar hemispheric white matter. Tau pathology and microgliosis were less prominent in the DN itself. The degree of myelin loss correlated with the tau burden in the SCP. GAP-43, which is a phosphoprotein known to be involved in axonal growth and sprouting, was decreased in the DN of PSP, and the degree of GAP-43 loss correlated with severity of GD. These results suggest that GD may be related to progressive pathology in the dentatorubrothalamic tract as well as the cerebellar hemispheric white matter, and that GD may be a consequence of concurrent degeneration in both output from and input to the DN. The results further suggest a possible role for oligodendroglial and myelin pathology in the pathogenesis of PSP.