[Influence of implantable Collamer lens implantation on choroidal thickness and blood flow density].

Objective: To observe the impact of implantable Collamer lens (ICL) implantation surgery on choroidal thickness and blood flow density in myopic patients. Methods: This was a prospective cohort study. Patients undergoing ICL surgery at Qingdao University Affiliated Hospital between June 2021 and May 2023 were consecutively enrolled. Patients were categorized into high myopia (HM) and super high myopia (SHM) groups based on whether their spherical equivalence power exceeded 10.00 D. Comprehensive ophthalmic examinations, including optical coherence tomography, optical coherence tomography angiography, visual acuity assessment, intraocular pressure measurement, and optometry, were performed preoperatively and at 1 week, 1 month, and 3 months postoperatively. Results: A total of 42 patients (84 eyes), with an average age of (25.27±3.18) years, comprising 11 males and 31 females, were enrolled in the study. Among them, 20 patients belonged to the HM group, while 22 patients were in the SHM group. Both choroidal thickness and blood flow density exhibited significant increases at postoperative 1 week and 1 month compared to preoperative levels (P<0.05), but returned to baseline levels by postoperative 3 months. Specifically, the subfoveal choroidal thickness increased from (169.49±61.57) µm preoperatively to (180.16±66.61) µm at 1 week, (186.69±63.32) µm at 1 month, and then reverted to (169.58±60.82) µm at 3 months. The central choroidal blood flow density showed changes from 60.03%±1.60% preoperatively to 61.04%±1.17% at 1 week, 60.42%±1.81% at 1 month, and 60.22%±1.57% at 3 months. Furthermore, the HM group exhibited more pronounced changes in both choroidal thickness and blood flow density across all time points compared to the SHM group. Significant differences were observed in choroidal thickness changes at various areas at 1 month, while changes in blood flow density in specific areas were significant. However, no significant differences were noted at 3 months postoperatively. Correlation analysis revealed a negative correlation of changes in subfoveal choroidal thickness and central choroidal blood flow density postoperatively at 1 week and 3 months with preoperative choroidal blood flow density. Notably, no correlation was found between preoperative choroidal thickness and postoperative changes. Conclusions: In the early period following ICL implantation, the increase in choroidal thickness and blood flow density may be more pronounced in HM compared to SHM, but the two parameters can return to baseline levels by 3 months. ICL implantation transiently affects the fundus microenvironment in myopic patients, with implications of preoperative choroidal blood flow.

[Study on formulation and revision of standard limits for radon in "Standards for indoor air quality (GB/T 18883-2022)" in China].

Public exposure to radon has attracted increasing public concern. The newly issued "Standards for indoor air quality (GB/T 18883-2022)" has revised the radiological parameters of radon. This study analyzed and discussed the relevant technical contents about the derivation of radon limit, including the distribution level for indoor radon, exposure pathway, health effects, and the process for establishing the standard limits. Specific implementation and evaluation suggestions are also proposed.

[Advances in neuromodulation of pulmonary hypertension].

Pulmonary hypertension is a progressive disease characterized by an increase in pulmonary vascular resistance, leading to unfavorable pulmonary vascular remodeling. This condition eventually leads to right ventricular hypertrophy and ultimately death from right ventricular failure. Although the exact pathogenesis of pulmonary hypertension remains unclear, autonomic nervous system dysfunction is recognized as one of the contributing factors. Increasing evidence supports the hypothesis that activation of the sympathetic nervous system plays a role in the development of pulmonary hypertension. In addition, pulmonary artery denervation has shown some effectiveness in the treatment of this condition. This article provides a comprehensive review of the neuroanatomical basis of the pulmonary vessels, the potential mechanisms underlying the onset and progression of pulmonary hypertension in relation to neuromodulation, and the application of neuromodulation techniques in its treatment.

Physical activity patterns, genetic susceptibility, and risk of hip/knee osteoarthritis: a prospective cohort study based on the UK Biobank.

OBJECTIVES: The effect of physical activity on hip/knee osteoarthritis (OA) and how it varies by genetic susceptibility to OA remains inconclusive. METHODS: In a cohort study of UK Biobank, 436,166 OA-free participants were recruited in 2006-2010 and followed for knee/hip OA until the end of 2020. 28 physical activity-related items were collected at baseline. Cox regression was used to estimate associations between physical activity behaviors, as well as major activity patterns (i.e., significant principal components[PCs] identified by principal component analysis), and risk of OA, adjusting for multiple confounders. We further stratified the analyses by polygenic risk score (PRS) for OA to examine the impact of genetic susceptibility to OA on the studied association. RESULTS: During a mean follow-up of 11.15 years, 13,227 hip and 21,119 knee OA cases were identified. 19, out of 28, studied items showed associations with increased OA risk. Compared with low adherence group(<1st tertile of PC score for each pattern), individuals with high adherence to five identified patterns were associated with increased risk of OA. The moderate adherence to "strenuous sports"(HR = 0.93, 95%CI: 0.89-0.97) and "walking for pleasure"(HR = 0.93, 95%CI: 0.89-0.98) patterns was associated with reduced OA. Similar risk patterns were obtained in the stratified analysis by PRS levels for OA. CONCLUSION: High intensity of most activity patterns were associated with increased OA. However, a protective effect was suggested for moderate adherence to patterns of "strenuous sports" and "walking for pleasure" that consistent across different genetic susceptibilities, underscoring the potential benefits of moderate-intensity physical activity on OA.

Associations between body composition and vertebral fracture risk in postmenopausal women.

INTRODUCTION: Osteoporosis is a metabolic bone disease with low bone mineral density (BMD) and high incidence of vertebral fractures (VFs). Postmenopausal women with osteoporosis have decreased total fat and lean mass. This study aimed to investigate the associations between body composition and VF risk and explore the potential predictor of VF risk in postmenopausal women. METHODS: Enrolled 731 postmenopausal women were referred by various departments and outpatient clinics to assess vertebral status between October 2016 and November 2017. The main measures were total body lean mass, fat mass, and BMD. Patients were divided into osteopenia, osteoporosis, and normal groups based on T-scores. Logistic regression analyses were performed to evaluate associations between body composition parameters and VF. RESULTS: VF was significantly associated with increased age, lower height, and lighter weight in all participants, and higher BMI was observed in VF participants. Participants in the osteoporosis group were older and had lower height, weight, and BMD than those in normal and osteopenia groups. Femoral and total hip T-scores as well as T-scores for lumbar spine were significantly lower in participants with VF than in non-VF participants. Percentage of bone mass was also significantly lower in VF participants compared to that of non-VF participants. Women with increased BMD and lower bone mass had reduced odds for VF occurrence. Bone mass was significantly able to identify VF occurrence. CONCLUSIONS: Body composition analysis discerns differences in the bone status of postmenopausal women with and without VF. The cutoff value of the bone mass might be used effectively as an indicator of risk for VF occurrence.

[Clinical effect of laparoscopic transcystic drainage combined with common bile duct exploration for the patients with difficult biliary stones].

OBJECTIVE: To explore the feasibility and efficacy of laparoscopic transcystic drainage and common bile duct exploration in the treatment of patients with difficult biliary stones. METHODS: Between April 2020 and December 2021, eighteen patients with difficult biliary stones received laparoscopic transcystic drainage (C-tube technique) and common bile duct exploration. The clinical characteristics and outcomes were retrospectively collected. The safety and effectiveness of laparoscopic transcystic drainage and common bile duct exploration were analyzed. RESULTS: Among the eighteen patients with difficult biliary stones, thirteen patients received traditional laparoscopic transcystic drainage, and the remaining five received modified laparoscopic transcystic drainage. The mean surgical duration were (161±59) min (82-279 min), no bile duct stenosis or residual stone was observed in the patients receiving postoperative cholangiography via C-tube. The maximum volume of C-tube drainage was (500±163) mL/d (180-820 mL/d). Excluding three patients with early dislodgement of C-tube, among the fifteen patients with C-tube maintained, the median time of C-tube removal was 8 d (5-12 d). The duration of hospital stay was (12±3) d (7-21 d) for the 18 patients. Five C-tube related adverse events were observed, all of which occurred in the patients with traditional laparoscopic transcystic drainage, including two abnormal position of the C-tube, and three early dislocation of the C-tube. All the 5 adverse events caused no complications. Only one grade one complication occurred, which was in a patient with modified laparoscopic transcystic drainage. The patient demonstrated transient fever after C-tube removal, but there was no bile in the drainage tube and the subsequent CT examination confirmed no bile leakage. The fever spontaneously relieved with conservative observation, and the patient recovered uneventfully with discharge the next day. All the 18 patients were followed up for 1-20 months (median: 9 months). Normal liver function and no recurrence of stone were detected with ultrasonography or magnetic resonance cholangiopancreatography (MRCP). CONCLUSION: Laparoscopic transcystic drainage combined with common bile duct exploration is safe and feasible in the treatment of patients with difficult biliary stones. The short-term effect is good. Modified laparoscopic transcystic drainage approach may reduce the incidence of C-tube dislocation and bile leak.

[Efficacy and safety of carotid endarterectomy combined with endovascular therapy in hybrid operating room for patients with segmental atherosclerotic internal carotid artery occlusion].

The current study aimed to investigate the efficacy and safety of carotid endarterectomy combined with endovascular therapy in hybrid operating room for patients with segmental atherosclerotic internal carotid artery occlusion, and share the experience of preoperative screening of patients suitable for vascular reconstruction. A total of 20 patients with internal carotid artery occlusion (ICAO) who were admitted to the Department of Neurosurgery, General Hospital of Tianjin Medical University from May 2018 to May 2020 were collected, and 15 patients met the inclusion criteria. All patients received hybrid surgery. The total success rate of recanalization was 14/15, and only 1 patient developed ICA re-occlusion at 1 year follow up.Therefore, carotid endarterectomy combined with endovascular treatment in hybrid operating room was an alternative treatment for patients with segmental atherosclerotic internal carotid artery occlusion.

[Mechanical analysis of the impact of the morphology of the iris and ciliary body on the central vault after posterior chamber phakic intraocular lens implantation].

Objective: To investigate the impact of the iris and ciliary body morphology on the central vault after phakic posterior chamber intraocular lens (pIOL) implantation. Methods: This research was based on the retrospective analysis of 123 patients (123 eyes) who underwent pIOL implantation in the Department of Ophthalmology, Affiliated Hospital of Qingdao University between June 2018 and June 2020. The anterior segment structure was observed with an ultrasound biomicroscope before surgery, and all morphological parameters of the iris and ciliary body were measured manually using the ImageJ software, including iris span (IS), iris convexity (IC), iris-ciliary body contact distance (ICCD) and iris-lens contact distance (ILCD). The ICCD was divided into Q1, Q2 and Q3 groups according to the equidistant distance of 0.36 mm. The lens thickness was measured with the IOLMaster. The horizontal corneal diameter and anterior chamber depth were measured using the Pentacam. The central vaults were measured by optical coherence tomography at 1 week, 3 months and 1 year after surgery. The relationships between vault values and preoperative parameters of the anterior segment were evaluated using the Pearson correlation analysis, Spearman correlation analysis, and multiple linear regression. The repeated measures ANOVA was applied to identify changes of vault values over time. Results: The mean values of the vaults at 1 week, 3 months and 1 year after surgery were (723±265) µm, (642±255) µm and (613±280) µm, respectively. The difference among them was statistically significant (F=50.143, P<0.001). The vaults continued to decline within 1 year after pIOL implantation, and the total decline was (122±86) µm. The vaults declined by (69±98) µm from postoperative 1 week to 3 months and by (52±54) µm from postoperative 3 months to 1 year. The regression formula showed that the pIOL size and ILCD were positively related with the vault, while the LT, IS and IC were negatively related with the vault at 1 week postoperatively (adjusted R²=0.404, P<0.001). The pIOL size and ILCD were positively related with the vault, while the IS and IC were negatively related with the vault at 3 months postoperatively (adjusted R²=0.342, P<0.001). The pIOL size was positively related with the vault, while the IS and IC were negatively related with the vault at 1 year postoperatively (adjusted R²=0.661, P<0.001). The vault values were higher in group Q3 compared to group Q1 at every timepoint, and the vault value was higher in group Q2 compared to Q1 at 1 year postoperatively. Conclusions: In the early postoperative period, eyes with a larger pIOL, shorter iris span, longer contact distance between the iris and ciliary body, and longer contact distance between the iris and lens were associated with a higher rate of excessive vaults. Meanwhile, eyes with a thicker lens and larger iris reverse convexity were more likely to obtain insufficient vaults. Within one year after surgery, the pIOL size, IS, IC and ICCD continued to impact on the vault. The ICCD, ILCD and IC can reflect the posterior chamber volume and change the haptic location and force, thus affecting the vault.

The biological characters of Bmelav-like genes in the development of Bombyx mori.

The ELAV/Hu family is a conserved multigene family of pan-neuronal RNA-binding protein involved in post-transcriptional regulation in metazoans. In Drosophila, three members of this family, ELAV, RBP9 and FNE, are involved in neuronal differentiation, gene expression regulation and so on. This family is less well characterized in Bombyx mori. Two orthologs BmELAV-like-1 (BmEL-1) and BmELAV-like-2 (BmEL-2) share 55%-71% and 47%-62% identity with that of in Drosophila and humans, respectively. Bmel-1 is ubiquitously expressed while Bmel-2 is expressed in the head and ovaries specifically. Proteins encoded by both genes are localized in nuclear and cytoplasm. The weight of body, cocoon, pupae and cocoon shell are differently affected in Bmel-1- /-2- mutants created using CRISPR/Cas9 technology. Mutations of both genes increase the expression of four silk protein genes, Fib-L, Fib-H, P25 and Ser-1. In addition, the oviposition ability of Bmel-2- females is decreased. This study not only provides valuable insights into the functional roles of Bmelav-like genes in the growth, cocoon characters and regulation of silk protein genes expression, but also provides useful information for silkworm variety breeding.

[Clinical observation of combined oral contraceptives drospirenone and ethinylestradiol tablets (â ¡) in the treatment of dysmenorrhea in Chinese women].

Objective: To evaluate the efficacy and safety of drospirenone and ethinylestradiol tablets (Ⅱ) in Chinese women with dysmenorrhea. Methods: This was a single-arm, open-label, interventional, multicenter, post-authorization safety/effectiveness study of drospirenone and ethinylestradiol tablets (Ⅱ) across 6 treatment cycles, a total of 526 patients were included in the dysmenorrhea subgroup. Visual analog scale (VAS) was used to assess the severity of menstrual pain. Secondary outcomes included unintended pregnancies, bleeding pattern, cycle control and safety. Results: After treated with drospirenone and ethinylestradiol tablets (Ⅱ), VAS of pain had decreased significantly compared with baselines [(49.5±23.7) vs (32.3±24.9) vs (20.7±19.4) vs (18.4±18.7) mm, P<0.01]. From the second cycle to the fifth cycle, the incidence of scheduled bleeding increased from 93.9% (450/479) to 96.4% (431/447). The duration of scheduled bleeding decreased from (5.7±2.7) to (5.4±1.8) days. The incidence of intermenstrual bleeding decreased from 9.0% (43/479) to 5.6% (25/447). 17.5% (92/526) patients reported adverse drug reactions, most frequently reported adverse events were breast pain, nausea, breast swelling, headache, and uterine bleeding. No death occurred during the study. Conclusion: Drospirenone and ethinylestradiol tablets (Ⅱ) is effective for the treatment of dysmenorrhea and has good safety.

[Progress in the application of pedicled autologous tissue in the repair of urethrorectal fistula].

The treatment of urethrorectal fistula remains challenging due to its rarity and complexity. The traditional operation mainly uses simple fistula repair, but the recurrence rate is high and the effect is poor. In recent years, a number of clinical retrospective studies have proved the feasibility of placing various kinds of pedicled tissue flap between the rectum and urethra, and its application has provided a new solution for the treatment of urethral rectal fistula, and achieved satisfactory results. Compared with traditional fistula repair, pedicled tissue flap has sufficient tissue thickness and clear blood supply, which makes up for the thin tissue and poor blood supply of urethral anastomosis and rectal fistula in traditional surgery, and significantly reduces the postoperative recurrence rate of urethral rectal fistula. On the other hand, there are differences in surgical approaches due to the different etiology, location, size of fistula mouth, and doctors' preferences. The anatomy and blood supply of all kinds of autologous pedicled tissue flaps also determine their clinical application. As a common disease of urology and colorectal surgery, the multidisciplinary collaboration of consultation and treatment has brought more options for the management of urethral rectal fistula. Based on this, in this paper, the application of various pedicled autologous tissues in the repair of urethrorectal fistula is reviewed, and different types of tissues are classified according to the surgical approach. The anatomy, blood supply, clinical application, indications, advantages and disadvantages of commonly used autogenous pedicled tissue are discussed in order to provide some reference for the repair of urethrorectal fistula.

[Corneal nerve repair and optical density in patients with high myopia after three kinds of corneal refractive surgery].

Objective: To investigate the repair of subepithelial nerve fibers in different areas of the cornea and the difference of corneal transparency 12 months after small incision lenticule extraction (SMILE), femtosecond laser in situ keratomileusis (FS-LASIK) and excimer laser in situ keratomileusis (LASEK) in high myopia. Methods: A cohort study. From June 2018 to October 2019, 30 patients with high myopia (60 eyes) were selected for corneal refractive surgery in the Department of Ophthalmology, Affiliated Hospital of Qingdao University, including 16 females (32 eyes) and 14 males (28 eyes). According to the mode of operation, the patients were divided into the SMILE group (n=10), FS-LASIK group (n=11) and LASEK group (n=9). The repair of subepithelial nerves in different areas of the cornea was observed by laser confocal microscopy 12 months after operation,and the morphological parameters were analyzed by ACCMetrics software. The parameters included corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), corneal nerve fiber total branch density (CTBD) and corneal nerve fiber width. The Pentacam anterior segment analyzer was used to measure the optical density of the cornea in different diameters. The nerve fiber parameters and corneal optical density were compared by random block analysis of variance, and multiple comparisons were performed between groups by the Turkey test. Results: Twelve months after operation, there was no significant difference in the CNFD among the three groups(all P>0.05). The CNBD around the upper corneal incision in the SMILE group, FS-LASIK group and LASEK group was (7.81±7.93), (9.61±7.18) and (21.25±15.55) branches/mm2, respectively. The CTBD was (22.00±16.02), (24.44±11.42) and (54.37±22.13) branches/mm2, respectively. The values in the LASEK group significantly differed from the other two groups (HSD=2.823, -3.010, 3.053, -3.048, P<0.01). The CNFL was (9.19±3.25), (12.88±3.52) and (15.75±2.36) mm/mm2, respectively. The value in the SMILE group was significantly different (HSD=-3.151, -4.418; P<0.0l). The corneal optical density after SMILE was 13.16±0.72 in the 0-6 mm diameter area(HSD=-4.164, -4.489; P<0.01), 16.12±3.18 in the 6-12 mm diameter area(HSD=-3.918, -3.493;P<0.01) and 14.06±1.36 in the total diameter (HSD=-6.031, -5.519;P<0.01), which differed significantly from the other two groups. Conclusions: Twelve months after SMILE for high myopia, the nerve repair around the superior corneal incision is slightly worse than that after FS-LASIK and LASEK, but the nerve repair in other areas has some advantages, and the corneal transparency is better. (Chin J Ophthalmol, 2021, 57:268-276).

Association of IL1R2 rs34043159 with sporadic Alzheimer's disease in southern Han Chinese.

BACKGROUND AND PURPOSE: The objective of the study was to investigate the relationship between IL1R2 rs34043159 and Alzheimer's disease (AD) in the Chinese population. METHODS: A total of 500 AD patients and 500 healthy controls were recruited. The SNaPshot technique was used to detect IL1R2 rs34043159. RESULTS: The dominant and recessive models of IL1R2 rs34043159 were associated with AD with or without adjustment of age, gender and education [dominant model, P = 0.019, odds ratio (OR) 1.42, 95% confidence interval (CI) 1.06-1.89, adjusted; recessive model, P = 0.011, OR 0.69, 95% CI 0.51-0.92, adjusted]. The recessive model of IL1R2 rs34043159 was associated with early-onset AD (EOAD) with or without adjustment of age, gender and education (recessive model, P = 0.038, OR 0.60, 95% CI 0.37-0.97, adjusted). The additive model was associated with late-onset AD (LOAD) (P = 0.041). The dominant model of IL1R2 rs34043159 was associated with LOAD with or without adjustment of age, gender and education (dominant model, P = 0.005, OR 1.68, 95% CI 1.17-2.44, adjusted). CONCLUSION: An association between the dominant and recessive model of IL1R2 rs34043159 and AD was found. The recessive model of IL1R2 rs34043159 was associated with EOAD. The additive and dominant models of IL1R2 rs34043159 were associated with LOAD.

[AMG-102 inhibits proliferation and induces apoptosis of laryngeal squamous cell carcinoma cells by regulating c-Met/PI3K/Akt pathway].

Objective: To investigate the effects of c-Met inhibitor AMG-102 on the proliferation and apoptosis of laryngeal squamous carcinoma Hep-2 cells and the underlying mechanism. Methods: Laryngeal squamous carcinoma cell line Hep-2 cells were treated with 2.5, 5 and 10 µmol/L AMG-102, respectively. The proliferation activities of Hep-2 cells were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT). The apoptotic rate of Hep-2 cells was detected by flow cytometry analysis and Hoechst staining. The mRNA expression levels of apoptosis-related genes were detected by real-time quantitative polymerase Chain reaction (RT-qPCR), and the protein expressions of c-Met/PI3K/AKT pathway were detected by western blot. Results: Compared with the control group, the proliferation rates of Hep-2 cells treated with 2.5, 5 and 10 µmol/L AMG-102 for 24 hours were (89.8±1.1)%, (79.8±1.0)% and (69.1±1.2)%, respectively; for 48 hours were (76.8±2.0)%, (60.2±1.1)% and (49.8±1.2)%, respectively; for 72 hours were (50.1±2.0)%, (41.5±1.1)% and (33.6±1.0), respectively, with significant differences (all P<0.05). The apoptotic rates of Hep-2 cells treated with 2.5, 5 and 10 µmol/L AMG-102 for 48 hours were (16.09±1.53)%, (27.51±2.02)% and (36.57±1.42)%, respectively, which were significantly higher than (3.62±0.10) % in the control group (all P<0.05). After treated with 2.5, 5 and 10 µmol/L AMG-102 for 48 hours, the relative expression levels of Bcl-2 mRNA in Hep-2 cells were 0.58±0.13, 0.38±0.12 and 0.20±0.13, respectively; the relative protein expression of p-Met were 80.0±3.8, 50.6±4.2 and 28.5±1.3, respectively; the relative protein expression of p-PI3K were 87.1±0.9, 54.2±1.2 and 21.0±1.2, respectively; the relative protein expression of p-AKT were 98.7±5.6, 56.9±3.2 and 32.2±4.3, respectively; which were significantly lower than those in the control group (all P<0.05). The relative expression levels of Bax mRNA were 1.78±0.13, 2.37±0.14 and 3.05±0.13, respectively, and the relative expression levels of caspase-3 mRNA were 1.98±0.14, 2.47±0.14 and 3.15±0.13, respectively, which were significantly higher than those in the control group (all P<0.05). Conclusion: c-Met inhibitor AMG-102 could inhibit the proliferation and induce apoptosis of laryngeal squamous carcinoma Hep-2 cells by regulating the c-Met/PI3K/Akt pathway.

[Clinical characteristics, treatment and prognosis of myelin oligodendrocyte glycoprotein antibody-associated optic neuritis in children].

Objective: To investigate the clinical characteristics, treatment and prognosis of myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) in pediatric patients. Methods: Clinical data, laboratory examination, the initial best corrected visual acuity (BCVA), fundus, neuroelectrophysiological results, MRI imaging, treatment and prognosis of children diagnosed with MOG-ON from 2016 to 2019 were retrospectively analyzed. Results: A total of 29 eyes from 16 children were involved, with a male/female ratio of 1∶1, onset age of (7.0±2.9) years. Seven of 16 patients had prodromal infection, with a unilateral/bilateral ratio of 3∶13, and 2 cases had recurrent optic neuritis. Before treatment, BCVA of 19 eyes (65.5%) was ≤0.1, among them, 4 had no sense of light, 5 had light sense, 5 with sense of hands in front of eyes, and 5 with sense of fingers in front of eyes. There were 10 eyes (34.5%) with BCVA of 0.1-0.5. After treatment, there were 4 eyes (13.8%), 5 eyes (17.2%) and 20 eyes (69.0%) in groups with BCVA of 0.1-0.5, 0.5-1.0, and>1.0, respectively. Twelve of 16 patients had optic papillitis in fundus examination during acute phase. The latency was prolonged and the amplitude was decreased in P100 wave of all the children. Thirteen out of 16 children showed swelling and thickening of optic nerve in MRI T2WI. MRI images exhibited intracranial demyelinating lesions in 12 of 16 children and long segment spinal cord lesions in 3 of 16 children. Thirteen of 16 patients showed effective results after intravenous methylprednisolone (IVMP) and intravenous immunoglobulin (IVIG) treatment. There was no relapse after administration of mycophenolate mofetil in 2 recurrent children. No progression after administration of rituximab was found in 1 child with corticosteroid insensitivity. The average follow-up time was (16±9) months and no recurrence occurred. Ten of 16 patients had full recovery, 4 had significant improvement, and 2 showed no significant improvement. Conclusions: There is no significant gender difference in the incidence of pediatric MOG-ON. Bilateral involvement and severe visual impairment are common in acute phase. Most patients have good response to IVMP combined with IVIG treatment and hence have a good prognosis. Only a few of them have neurological sequelae.

[Clinical features and prognosis of pediatric myelin oligodendrocyte glycoprotein antibody associated acute disseminated encephalomyelitis].

Objective: To analyze the clinical features, outcome and prognosis of pediatric myelin oligodendrocyte glycoprotein (MOG) antibody associated acute disseminated encephalomyelitis (ADEM), and provide evidence for improving the diagnosis and treatment of this disease. Methods: This study involved 30 MOG antibody-associated ADEM patients in the Department of Neurology, Guangzhou Women and Children's Medical Center. Patients' clinical information were analyzed. Results: The mean onset age was (5.2±3.3) years old, the ration of male to female was 16∶14. Fifty percent of these patients had a history of precede infection or vaccination before onset. Encephalopathy and seizures were the most common clinical manifestations, followed by movement disorder. In addition, some patients had other positive autoantibodies. Brain Magnetic resonance imaging (MRI) showed extensive, asymmetrical, indefinite large patchy lesions in bilateral cortical and subcortical areas and the spinal cord was characterized by long segmental myelitis. In acute attack, the patients had a good response to corticosteroid combined immunoglobulin therapy. Most of these patients had a good prognosis and recurrence rate was about 20%. Conclusions: The onset age of MOG antibody-associated ADEM is around 5 years old. Encephalopathy and seizures were the most common clinical manifestations. Most patients have a good response to corticosteroid combined immunoglobulin therapy. Some patients may have a recurrent disease course.

[Construction of disease assessment index of silicosis patients].

Objective: To explore the establishment of disease assessment index model in silicosis patients. Methods: In October 2018, 171 silicosis patients who were hospitalized from November 2014 to November 2015 were selected as the study subjects. According to the standard of death risk, the subjects were divided into two groups, including the group without death risk (153 cases) and the group with death risk (18 cases) . Through literature analysis and clinical experience, the variables related to silicosis were preliminarily screened. Multifactorial logistic regression analysis variables were used to analyze the relationship between the variables and the risk of death. The variables associated with the risk of death were selected as the final variables to establish the disease assessment index model. And the receiver operating characteristic (ROC) curve was used to evaluate the clinical application of the disease assessment index. Results: Five variables of Modified British Medical Research Council Respiratory Questionnaire (mMRC) , pulmonary function injury, pneumoconiosis stage, aggravation of the disease and complications were selected as the variables of the disease assessment index, and the assessment index score ranged from 1 to 11 points. The area under the ROC curve of disease assessment index was 0.747 (95%CI: 0.590-0.904) , which could better identify the death risk of silicosis patients. With the increase of disease assessment index score, the death risk of silicosis patients increased. When the cutoff value was 7, the sensitivity and specificity were 0.667 and 0.876, respectively, for the risk of death of silicosis patients. The results of cross-validation showed that the correct discrimination rate of the disease assessment index to the risk of death was 66.7%. Conclusion: The disease assessment index can predict the death risk of patients with silicosis, and can evaluate the disease comprehensively.

Ultra-deep next-generation sequencing of plasma cell-free DNA in patients with advanced lung cancers: results from the Actionable Genome Consortium.

BACKGROUND: Noninvasive genotyping using plasma cell-free DNA (cfDNA) has the potential to obviate the need for some invasive biopsies in cancer patients while also elucidating disease heterogeneity. We sought to develop an ultra-deep plasma next-generation sequencing (NGS) assay for patients with non-small-cell lung cancers (NSCLC) that could detect targetable oncogenic drivers and resistance mutations in patients where tissue biopsy failed to identify an actionable alteration. PATIENTS AND METHODS: Plasma was prospectively collected from patients with advanced, progressive NSCLC. We carried out ultra-deep NGS using cfDNA extracted from plasma and matched white blood cells using a hybrid capture panel covering 37 lung cancer-related genes sequenced to 50 000× raw target coverage filtering somatic mutations attributable to clonal hematopoiesis. Clinical sensitivity and specificity for plasma detection of known oncogenic drivers were calculated and compared with tissue genotyping results. Orthogonal ddPCR validation was carried out in a subset of cases. RESULTS: In 127 assessable patients, plasma NGS detected driver mutations with variant allele fractions ranging from 0.14% to 52%. Plasma ddPCR for EGFR or KRAS mutations revealed findings nearly identical to those of plasma NGS in 21 of 22 patients, with high concordance of variant allele fraction (r = 0.98). Blinded to tissue genotype, plasma NGS sensitivity for de novo plasma detection of known oncogenic drivers was 75% (68/91). Specificity of plasma NGS in those who were driver-negative by tissue NGS was 100% (19/19). In 17 patients with tumor tissue deemed insufficient for genotyping, plasma NGS identified four KRAS mutations. In 23 EGFR mutant cases with acquired resistance to targeted therapy, plasma NGS detected potential resistance mechanisms, including EGFR T790M and C797S mutations and ERBB2 amplification. CONCLUSIONS: Ultra-deep plasma NGS with clonal hematopoiesis filtering resulted in de novo detection of targetable oncogenic drivers and resistance mechanisms in patients with NSCLC, including when tissue biopsy was inadequate for genotyping.

Characterization of microbial community profiles associated with quality of Chinese strong-aromatic liquor through metagenomics.

AIMS: Microorganisms in fermentation pits (FPs) play key roles for Chinese-strong-aromatic-liquor (CSAL) production. However, the microbial community in the FPs is still poorly understood. Here, the aim of this study was to reveal the diversity and potential functions of microbiota in FPs. METHODS AND RESULTS: Sequencing-by-synthesis-based metagenomic sequencing and annotation results revealed that the microbiota of FPs was primarily composed of Firmicutes (54·6%), Euryarchaeota (15·3%), Bacteroidetes (10·1%), Gammaproteobacteria (5·8%), Opisthokonta (5·7%) and Unclassified_Bacteria (2·3%). And 133 genera were identified as the dominant genera of this fermentative food. Lactobacillus, Sedimentibacter, Syntrophomonas, Methanoculleus, Methanobacterium, Bacillus, Clostridium, Galactomyces, Candida, Pichia, Penicillium and Aspergillus were defined as active populations for biosynthesizing the characteristic volatile compounds of CSAL. The study also revealed that the microbial community structures changed significantly with different cellar ages and over different geographical regions. (i) The presence of Bacteroidetes was the most distinctive feature that characterized the different FPs ages. (ii) Distinct contents of Gammaproteobacteria and Euryarchaeota were observed at different positions in the FPs. (iii) Euryarchaeota markedly contributed to the generation of the character of the liquors with distinct geographical associations. CONCLUSIONS: This study demonstrated that the changes of microbial communities determined the different quality characteristics of CSAL. SIGNIFICANCE AND IMPACT OF THE STUDY: This research contributes to a deeper understanding of the FPs microbial composition and shows a new microbial resource for biotechnological applications.

[Effect of c-Met inhibitor AMG-102 on radiosensitivity in laryngeal squamous carcinoma cells].

Objective: To investigate the effect of c-Met inhibitor AMG-102 on proliferation and radiosensitivity in laryngeal squamous carcinoma cells. Methods: The effects of AMG-102 on proliferation and radiosensitivity of laryngeal squamous carcinoma cell lines Hep-2 and KBV200 were detected by 3-(4, 5-dimethy-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay and colony formation assay, respectively. The apoptosis of Hep-2 and KBV200 cells was detected by flow cytometry. The expression levels of c-Met, phospho-Met (p-Met), cleaved caspase-3 and Akt/p-Akt, Erk/p-Erk were detected by Western blot. Specific small interfering RNA targeting c-Met or plasmid of c-Met were transfected into Hep-2 and KBV200 cells to investigate the cell sensitivity to AMG-102. Results: Compared with KBV200 cells, Hep-2 cells were more sensitive to AMG-102 with IC(50) of 14 and 9 µmol/L, respectively. The relative expression levels of c-Met and p-Met proteins in Hep-2 cells were 194.48±0.57 and 177.76±1.53, respectively, which were significantly higher than those in KBV200 cells (171.24±1.00 and 115.37±0.56, respectively, P<0.001 for both). Exogenous hepatocyte growth factor (HGF) was added to increase the expression level of p-Met protein in KBV200 cells. The results showed that AMG-102 significantly reduced the expression of p-Met in KBV200 cells treated with HGF (P<0.001). Compared with the dimethyl sulfoxide (DMSO) group, AMG-102 treatment combined with radiotherapy significantly increased the radiosensitivity of Hep-2 cells (SER=1.28, P<0.001). However, AMG-102 had little effect on the radiosensitivity of KBV200 cells (SER=1.18, P=0.002). Compared with the 4 Gy radiotherapy alone group and the 5 µmol/L of AMG-102 alone treatment group, the apoptosis rate of Hep-2 cells in the combined treatment group was significantly increased. Meanwhile, the expression level of cleaved caspase-3 protein was also markedly increased. However, there were no significant changes in the apoptotic rate and cleaved caspase-3 expression in each treatment group of KBV200 cells. Compared with DMSO treatment group, the expression levels of p-Met, p-Akt and p-Erk were significantly decreased in the 4 Gy radiotherapy group, 5 µmol/L of AMG-102 treatment group and combined treatment group of Hep-2 cells. And the levels of p-Met, p-Akt and p-Erk in the combined treatment group were significantly lower than those in the 4 Gy radiotherapy alone group and 5 µmol/L of AMG-102 treatment alone group. By contrast, in KBV200 cells, the expression of p-Met, p-Akt and p-Erk in each group was not changed. The relative expression of p-Met in Hep-2 cells before and after radiotherapy at 30 min, 1 h, 4 h, 8 h, 24 h were 99.89±0.61, 138.62±1.00, 163.07±5.00, 87.80±1.85, 90.67±0.65 and 94.09±1.41, respectively. The level of p-Met was slightly increased after radiotherapy at 30 min and 1 h (P<0.001 for all), whereas it was significantly decreased from 4 h to 24 h after radiotherapy (P<0.05 for all). By contrast, the expression of p-Met in KBV200 cells did not change with time after radiotherapy (P>0.05). The sensitivity of Hep-2 cells to AMG-102 was decreased after silencing of c-Met, while the sensitivity of KBV200 cells to AMG-102 was not significantly changed (P>0.05). Moreover, the radiosensitivity of Hep-2 cells in c-Met knockdown group had a slightly increasing trend (SER=1.07, P=0.068). After the treatment with 10 µmol/L of AMG-102, the proliferation rate of c-Met ectopically expressed KBV200 cells was 60.05%±3.23%, It was significantly lower than that of the blank control 90.08%±1.04% and siRNA negative control (90.12%±1.01%, P<0.001). The results suggested that the overexpression of c-Met in KBV200 cells increased the radiosensitivity to AMG-102, whereas depletion of c-Met resulted in resistance to AMG-102 in Hep-2 cells. Furthermore, the radiosensitivity of KBV200 cells that overexpressed c-Met showed a decreased trend (SER=0.7, P=0.005). Conclusions: c-Met inhibitor AMG-102 has a significant inhibitory effect on the proliferation of c-Met overexpressing laryngeal squamous carcinoma cells, leading to increased radiosensitivity. It suggests that molecular targeted therapy against c-Met receptor is more effective in c-Met overexpressed subtype of laryngeal squamous cell carcinoma.