[Imaging features of posterior polymorphous corneal dystrophy observed by in vivo confocal microscopy].

Objective: To identify and analyze imaging features of posterior polymorphous corneal dystrophy (PPCD) by in vivo confocal microscopy (IVCM). Methods: This retrospective case series enrolled 27 eyes of 18 patients (including 10 males and 8 females) who were diagnosed with PPCD at the Department of Ophthalmology in Peking University Third Hospital between January 2013 and December 2019. The mean age was (23.61±14.81) years. There were 9 monocular and 9 binocular cases. All patients were examined by slit-lamp biomicroscopy and IVCM. The visual acuity, the mean endothelial cell density, and the images of IVCM were analyzed in all cases. Results: The mean best-corrected visual acuity was 0.76±0.33, and the mean endothelial cell density was (1 723.6±698.3) cells/mm2. The IVCM images of type 1 PPCD (vesicular lesions) showed hyperreflective, placoid or homocentric lesions at the level of the Descemet's membrane, hyporeflective, oval or round lesions at the level of the Descemet's membrane, and hyporeflective, crater-like lesions at the level of the endothelial cell layer. The IVCM images of type 2 PPCD (band lesions) displayed hyperreflective, band lesions and a fibrous strand structure at the level of the Descemet's membrane, hyporeflective, vesicular lesions at the level of the Descemet's membrane, and hyporeflective, trough-and ridge-like lesions at the level of the endothelial cell layer. The IVCM images of type 3 PPCD (geographic placoid opacities) showed loss of the hexagonal features of endothelial cells and epithelial-like cell transformation. Conclusions: PPCD primarily affects the endothelium and Descemet's membrane. IVCM could highlight the special characteristics of PPCD including hyperreflective lesions at the level of the Descemet's membrane, hyporeflective lesions at the level of the endothelial cell layer, and epithelial-like cell transformation of endothelial cells. IVCM is an invaluable tool for clinical diagnosis and dynamic monitoring of PPCD.

[Descemet membrane endothelial keratoplasty in initial cases: analysis and management of surgical complications].

Objective: To investigate causes and management of surgical complications of Descemet membrane endothelial keratoplasty (DMEK) in initial cases. Methods: A retrospective study. A total of 52 eyes of 52 patients underwent DMEK by one surgeon in Peking University Third Hospital from February 2017 to December 2019, including 17 males and 35 females, aged (66±12) years. All patients' demographic characteristics, previous surgical history, intraoperative and postoperative complications were recorded. Results: Intraoperative complications included difficulties in unfolding the graft in 6 cases (11.5%), inverted grafts in 5 cases (9.6%), grafts rushing out of the anterior chamber in 2 cases (3.8%), grafts injected behind the iris in 3 cases (5.8%) and hemorrhage in 1 case. Partial graft detachment that occurred in 28 cases (53.8%) was the most frequent postoperative complication. Rebubbling was performed in 25 cases (48.1%). Pupillary block occurred in 9 cases (17.3%) and was managed by reducing air under a slit lamp. Primary graft failure occurred in 3 cases (5.8%) and viral infection occurred in 2 cases (3.8%). Conclusions: The rate of complications of DMEK in initial cases is higher than that of Descemet stripping automated endothelial keratoplasty. Intraoperative graft inversion and postoperative graft detachment are the most common complications. It is important to select appropriate indications and discover or manage intraoperative and postoperative complications in time to reduce the incidence of complications. (Chin J Ophthalmol, 2021, 57:595-600).

[The 8-year follow-up study for clinical diagnostic potentials of frequency-doubling technology perimetry for perimetrically normal eyes of open-angle glaucoma patients with unilateral visual field loss].

Objective: To analyze potentials of frequency-doubling technology perimetry (FDP) for diagnosing open-angle glaucoma (OAG) in perimetrically normal eyes of OAG patients diagnosed with standard automated perimetry (SAP) and relating factors from abnormalities on FDP to visual field loss on SAP. Methods: A prospective cohort study. Sixty-eight eyes of 68 OAG patients visiting the ophthalmic clinic of Peking University Third Hospital during November 2003 and October 2007 [32 primary open-angle glaucoma patients and 36 normal tension glaucoma patients, 32 males and 36 females, with an average age of (59±13) years] with unilateral field loss detected by SAP (Octopus101 tG2 program) were examined with the FDP N-30 threshold program (Humphrey Instruments) at baseline. Two groups, FDP positive group and FDP negative group, were divided based on the FDP results, and visual field examinations were followed by a series of SAP examinations for the perimetrically normal eyes over 8 years. During the follow-up, the difference of the converting rate of SAP tests between the two groups was analyzed. Differences between "convertors" and "non-convertors" of SAP tests in the FDP positive group, such as the cup-to-disk ratio and glaucomatous optic neuropathy rate, were also compared with the independent-sample t test or Wilcoxon two-sample test for continuous variable data and the χ(2) test or Fisher exact test for classified variable data and rates. Results: Forty-eight perimetrically normal eyes of 48 participants had complete data and a qualifying follow-up. Baseline FDP results were positive in 33 eyes and negative in 15 eyes. Of the eyes with positive FDP results, 22 eyes developed abnormal SAP results after 4.0 to 90.0 months (median 14.5 months) , whereas none of the eyes with negative FDP results developed abnormal SAP results. For perimetrically normal eyes in the FDP positive group, "converters" showed a greater cup-to-disk ratio (0.73±0.09 vs. 0.63±0.14, Wilcoxon two-sample test, P=0.011) and more eyes with glaucomatous optic neuropathy (19/22 vs. 4/11, Fisher exact test, P=0.006). Conclusions: In perimetrically normal eyes of OAG patients, FDP could detect visual field loss of these eyes and predict to some extent future visual field loss on SAP. Severity of glaucomatous optic neuropathy at baseline is related to converting from abnormalities on FDP to visual field loss on SAP. (Chin J Ophthalmol, 2018, 54: 177-183).

ATP2C1 gene mutations in Hailey-Hailey disease and possible roles of SPCA1 isoforms in membrane trafficking.

ATP2C1 gene codes for the secretory pathway Ca(2+)/Mn(2+)-ATPase pump type 1 (SPCA1) localizing at the golgi apparatus. Mutations on the human ATP2C1 gene, causing decreased levels of the SPCA1 expression, have been identified as the cause of the Hailey-Hailey disease, a rare skin disorder. In the last few years, several mutations have been described, and here we summarize how they are distributed along the gene and how missense mutations affect protein expression. SPCA1 is expressed in four different isoforms through alternative splicing of the ATP2C1 gene and none of these isoforms is differentially affected by any of these mutations. However, a better understanding of the tissue specific expression of the isoforms, their localization along the secretory pathway, their specific binding partners and the role of the C-terminal tail making isoforms different from each other, will be future goals of the research in this field.

The Warburg effect: a balance of flux analysis.

Cancer metabolism is characterized by increased macromolecular syntheses through coordinated increases in energy and substrate metabolism. The observation that cancer cells produce lactate in an environment of oxygen sufficiency (aerobic glycolysis) is a central theme of cancer metabolism known as the Warburg effect. Aerobic glycolysis in cancer metabolism is accompanied by increased pentose cycle and anaplerotic activities producing energy and substrates for macromolecular synthesis. How these processes are coordinated is poorly understood. Recent advances have focused on molecular regulation of cancer metabolism by oncogenes and tumor suppressor genes which regulate numerous enzymatic steps of central glucose metabolism. In the past decade, new insights in cancer metabolism have emerged through the application of stable isotopes particularly from 13C carbon tracing. Such studies have provided new evidence for system-wide changes in cancer metabolism in response to chemotherapy. Interestingly, experiments using metabolic inhibitors on individual biochemical pathways all demonstrate similar system-wide effects on cancer metabolism as in targeted therapies. Since biochemical reactions in the Warburg effect place competing demands on available precursors, high energy phosphates and reducing equivalents, the cancer metabolic system must fulfill the condition of balance of flux (homeostasis). In this review, the functions of the pentose cycle and of the tricarboxylic acid (TCA) cycle in cancer metabolism are analyzed from the balance of flux point of view. Anticancer treatments that target molecular signaling pathways or inhibit metabolism alter the invasive or proliferative behavior of the cancer cells by their effects on the balance of flux (homeostasis) of the cancer metabolic phenotype.

A school outbreak of Shigella sonnei infection in China: clinical features, antibiotic susceptibility and molecular epidemiology.

OBJECTIVE: To describe the clinical features of infection, and the antibiotic susceptibility of epidemic strains, and investigate plasmid maps and integrons of the isolates from an outbreak of Shigella sonnei infection at an elementary school in southwest China. STUDY DESIGN: Cross-sectional study. SETTING: An elementary school and five hospitals in Chengdu in southwest China. RESULTS: There were 1,134 students in the school. 937 (82.6%) students had signs and symptoms. Of the 568 (60.6%, 568/937) hospitalized students, 93.3% 86.8%, 72.4%, and 28.9% of the hospitalized patients had diarrhea, fever, abdominal pain, and vomiting, respectively. S. sonnei strains were isolated from the stool samples of 36.0% (337/937) students. All of the outbreak isolates had the same high-level antimicrobial resistance and plasmid profiles, which were different from that of sporadic strains. All the outbreak S. sonnei isolates were positive for the integrin gene and contained class 2 integron; however, two outbreak isolates contained class 1 and class 2 integrons. CONCLUSIONS: Diarrhea, fever, and abdominal pain were the three most common clinical manifestations observed in patients infected with S. sonnei. High-level antibiotic resistance was observed among Shigella species.

Adipocytes derived from human bone marrow mesenchymal stem cells exert inhibitory effects on osteoblastogenesis.

The infiltration of adipocytes in osteoporotic patients' bone marrow suggests an important regulatory function of bone marrow fat on the development of aged bone. Therefore, we have examined the effects of adipocytes derived from bone mesenchymal stem cell (MSC) on osteoblast differentiation using two different co-culture modes (direct mode and indirect mode). Alkaline phosphatase (ALP)-positive areas and mineralized areas of MSC-derived osteoblasts decrease similarly in the two co-culture modes as the amount of MSC-derived adipocytes increases, suggesting that the crosstalk between adipocytes and osteoblasts may be mainly through secretory factors in the medium. To further understand the molecular mechanisms, both mRNA and protein expressions in osteoblasts in the lower layer of the indirect mode were analyzed, leading to identification of 12 differential genes/proteins. Among them, S100A6 and calreticulin are possibly related to bone formation. S100A6 was down-regulated and calreticulin was up-regulated as MSC-derived adipocytes increased. Similarly, differential expression of these proteins was also observed in bone tissue slides from young (1-month-old) and old (6-month-old) mice. The expression level of ß-catenin in osteoblasts of bone tissues was lower in 6-month-old mice compared to 1-month-old mice. Total TGF-ß analyzed with antibody-based protein microarray and active TGF-ß analyzed with ELISA in the co-cultured cell medium increased consistently as the amount of adipocytes increased. Taken together, our results suggest that MSC-derived adipocytes may regulate osteoblast differentiation in the aged bone through TGF-ß-mediated canonical Wnt signaling.

Laser spectroscopy using beam-overlap modulation.

A new Doppler-free laser spectroscopy method is demonstrated that employs modulation of the position of a laser beam rather than the commonly used intensity or polarization modulation. The technique is applicable in saturated absorption as well as fluorescence measurements, as is illustrated in experiments on sodium and iodine lines. A particular feature of the method is that Doppler- and background-free fluorescence spectra can be recorded without using intermodulation techniques.