Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022)

Background In China's Mainland,patients with neovascular age-related macular degeneration(nAMD)have approximately an 40%prevalence of polypoidal choroidal vasculopathy(PCV).This disease leads to recurrent retinal pigment epithelium detachment(PED),extensive subretinal or vitreous hemorrhages,and severe vision loss.China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes,regarding opinions on inactive PCV,choices of anti-vascular endothelial growth factor(anti-VEGF)monotherapy,photodynamic therapy(PDT)monotherapy or combined therapy,patients with persistent subretinal fluid(SRF)or intraretinal fluid(IRF)after loading dose anti-VEGF,and patients with massive subretinal hemorrhage.An evidence synthesis team conducted systematic reviews,which informed the recommendations that address these questions.This guideline used the GRADE(Grading of Recommendations,Assessment,Development,and Evaluation)approach to assess the certainty of evidence and grade the strengths of recommendations.Results The panel proposed the following six conditional recommendations regarding treatment choices.(1)For patients with inactive PCV,we suggest observation over treatment.(2)For treatment-na?ve PCV patients,we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy.(3)For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment,we suggest later/rescue PDT over initiate PDT.(4)For PCV patients who plan to initiate anti-VEGF monotherapy,we suggest the treat and extend(TE)regimen rather than the pro re nata(PRN)regimen following three monthly loading doses.(5)For patients with persistent SRF or IRF on optical coherence tomography(OCT)after three monthly anti-VEGF treatments,we suggest proceeding with anti-VEGF treatment rather than observation.(6)For PCV patients with massive subretinal hemorrhage(equal to or more than four optic disc areas)involving the central macula,we suggest surgery(vitrectomy in combination with tissue-plasminogen activator(tPA)intraocular injection and gas tamponade)rather than anti-VEGF monotherapy.Conclusions Six evidence-based recommendations support optimal care for PCV patients'management.

A GPCR/secretase complex regulates β- and γ-secretase specificity for Aβ production and contributes to AD pathogenesis

Dysregulation of β-site APP-cleaving enzyme （BACE） and/or γ-secretase leads to anomalous production of amyloid-β peptide （Aβ） and contributes to the etiology of Alzheimer＇s disease （AD）. Since these secretases mediate proteolytic processing of numerous proteins, little success has been achieved to treat AD by secretase inhibitors because of inevitable undesired side effects. Thus, it is of importance to unravel the regulatory mechanisms of these secretases. Here, we show that δ-opioid receptor （DOR） promotes the processing of Aβ precursor protein （APP） by BACE1 and γ-secretase, but not that of Notch, N-cadherin or APLP. Further investigation reveals that DOR forms a complex with BACE1 and γ-seeretase, and activation of DOR mediates the co-endocytic sorting of the secretases/ receptor complex for APP endoproteolysis. Dysfunction of the receptor retards the endocytosis of BACE1 and γ-secretase and thus the production of Aβ Consistently, knockdown or antagonization of DOR reduces secretase activities and ameliorates Aβ pathology and Aβ-dependent behavioral deficits, but does not affect the processing of Notch, N-cadherin or APLP in AD model mice. Our study not only uncovers a molecular mechanism for the formation of a DOR/secretase complex that regulates the specificity of secretase for Aβ production but also suggests that intervention of either formation or trafficking of the GPCR/secretase complex could lead to a new strategy against AD, potentially with fewer side effects.

Long-term follow-up of vitrectomy in patients with pathologic myopic foveoschisis

AIM： To report the long-term surgical outcomes of pathologic myopic foveoschisis（MF） following vitrectomy.METHODS： We performed a retrospective case series analysis of 50 consecutive patients diagnosed with MF who experienced vision loss due to progression of foveoschisis.The 50 patients（67 eyes） were treated in our hospital with vitrectomy with internal limiting membrane（ILM） peeling from December 2004 to September 2010.Best corrected visual acuity（BCVA）,refractive error,optical coherence tomography（OCT）,and routine examination results were analysed.The changes of BCVA,foveal anatomical features on OCT scan,and complications were the main outcome measures.RESULTS： The mean follow-up duration was 42±17mo（range 24 to 93mo）.BCVA improved significantly postoperatively（0.76±0.65 logM AR） compared with preoperative baselines（1.31±0.78 log MAR,P〈0.0001）,and in 53 eyes（79%） including 3 lines gain in 44 eyes（66%） at the last follow-up visit.OCT scans showed that central retinal thickness decreased from 580.0±270.0 μm preoperatively（n=67） to 179.7±84.7 μm postoperatively（n=58,P〈0.0001）.Total resolution of foveoschisis occurred in 41 eyes（61%）.Preoperative BCVA correlated well with postoperative BCVA,whereas other factors such as age,axial length,and refractive error were not correlated.The most common complications were cataract and full-thickness macular hole formation in 14 and 9 cases,respectively.CONCLUSION： Patients with progressive vision loss due to MF who were treated with vitrectomy with ILM peelingshow favourable outcomes.In most eyes,visual acuity and foveal structure remain stable during long-term observation.

Ferucarbotran versus Gd-DTPA-enhanced MR imaging in the detection of focal hepatic lesions

AIM: To evaluate the efficacy of ferucarbotran-enhanced MR imaging in the detection of focal hepatic lesions compared to plain and Gd-DTPA-enhanced MR imaging. METHODS: Fifty-nine patients with suspected focal hepatic lesions were admitted to the study. Plain MR imaging (FSE T2WI with fat suppression and GRE T1WI sequences) and Gd-DTPA dynamic enhanced MR of the liver were initially performed followed by ferucarbotran- enhanced MR imaging 48 h later (including GRE T1WI, FSE T2WI with fat suppression, and GRE T2*WI sequences). Images were reviewed independently by three observers. Results were correlated with surgery and pathologic examination or reference examination, and sensitivity was statistically calculated for the different MR imaging sequences. RESULTS: Among all confirmed lesions (n = 133), ferucarbotran-enhanced MR imaging revealed 130 lesions on FSE T2WI with fat suppression, 115 lesions on dynamic T1WI GRE, and 127 lesions on GRE T2*WI. Pre-contrast MR imaging revealed only 84 lesions on GRE T1WI and 106 lesions on FSE T2WI with fat suppression, while Gd-DTPA dynamic enhanced GRE T1WI revealed 123 lesions. For 44 micro-lesions (< 1.0 cm) in all patients the detection rates were as follows: ferucarbotran-enhanced FSE T2WI with fat suppression, 93.2% (41/44); ferucarbotran-enhanced GRE T2*WI, 88.6% (39/44); Gd-DTPA dynamic-enhanced GRE T1WI, 79.5% (35/44); pre-contrast FSE T2WI with fat suppression, 54.5% (24/44); and pre-contrast GRE T1WI, 34.1% (15/44). In detecting micro-lesions, statistically significant difference was found for Ferucarbotran- enhanced FSE T2WI with fat suppression and GRE T2*WI sequences compared to the other sequences (P < 0.05).CONCLUSION: Ferucarbotran-enhanced FSE T2WI with fat suppression and GRE T2*WI sequences are superior in detecting micro-lesions (< 1 cm) in comparison with plain and Gd-DTPA dynamic-enhanced MR imaging.

Trichosanthin functions as Th2-type adjuvant in induction of allergic airway inflammation

It is important to understand the pathogenesis of asthma induced by natural allergens, which could exclude the interference of artificial adjuvant and provide insights of natural immune response in the disease. In the present study, we show that Trichosanthin （TCS） could induce airway inflammation even without the help of alum. Furthermore, TCS appeared capable of replacing alum to promote OVA-specific airway inflammation. TCS induced accumulation of IL-4-producing eosinophils in peritoneum at an early stage and the adjuvant function of TCS was eliminated by blockage of IL-4 at this stage. Finally, the eosinophils triggered by TCS from WT mice, but not from IL-4- deficient mice were shown to function as adjuvant for the induction of OVA-specific Th2 responses. Our data indicate that TCS is not only an allergen, but also a Th2-typc adjuvant modulating the switching of immune responses to a Th2 pathway. This chain of events results from IL-4 production by eosinophils at an early stage of TCS-priming. In conclusion, TCS may be useful as a Th2 adjuvant, and innate immune cells, such as eosinophils, may be a good target to study the initiation of Th2 response.

Congenital Vaginal Atresia:A Report of 39 Cases in a Regional Obstetrics and Gynecology Hospital

To investigate the clinical course and management of congenital vaginal atresia. This retrospective analysis included patients with congenital vaginal atresia treated from March 2004 to August 2014 at the Obstetrics and Gynecology Hospital of Fudan University. Thirty-nine patients were included in this study. Their average age was 16.87±2.2 years when they came to our hospital. Totally, 51% of the patients had isolated congenital vaginal atresia with a normal cervix, whereas the others had either cervical atresia or imperforate hymen. The primary presenting signs and symptoms included primary amenorrhea（71.8%）, periodic abdominalgia（41.0%）, abdominal pain（36.0%）, dyspareunia（10.3%）, menstrual disorders（5.1%）, and pelvic mass（5.1%）. Ultrasound and magnetic resonance imaging（MRI） were effective inspection methods for the screening of urogenital tract-associated anomalies. Vaginoplasty mainly included simple vagina reconstruction with insertion of a mold（n=22） and split-thickness skin grafting（n=4）. In 64% of surgical patients, normal menstrual bleeding was achieved. Four of the patients subsequently became pregnant and delivered at term. Primary amenorrhea, periodic abdominalgia and abdominal pain are the main reasons for the post pubertal patients to visit doctors. Surgical methods can successfully provide these patients an opportunity for subsequent conservative management, can result in normal menstrual bleeding, resolve cyclic pelvic pain, and provide some potential for fertility.

Identification of potential candidate proteins for reprogramming spinal cord-derived astrocytes into neurons:a proteomic analysis

Our previous study has confirmed that astrocytes overexpressing neurogenic differentiation factor 1(NEUROD1)in the spinal cord can be reprogrammed into neurons under in vivo conditions.However,whether they can also be reprogrammed into neurons under in vitro conditions remains unclear,and the mechanisms of programmed conversion from astrocytes to neurons have not yet been clarified.In the present study,we prepared reactive astrocytes from newborn rat spinal cord astrocytes using the scratch method and infected them with lentivirus carrying NEUROD1.The results showed that NEUROD1 overexpression reprogrammed the cultured reactive astrocytes into neurons in vitro with an efficiency of 13.4%.Using proteomic and bioinformatic analyses,1952 proteins were identified,of which 92 were differentially expressed.Among these proteins,11 were identified as candidate proteins in the process of reprogramming based on their biological functions and fold-changes in the bioinformatic analysis.Furthermore,western blot assay revealed that casein kinase II subunit alpha(CSNK2A2)and pinin(PNN)expression in NEUROD1-overexpressing reactive astrocytes was significantly increased,suggesting that NEUROD1 can directly reprogram spinal cord-derived reactive astrocytes into neurons in vitro,and that the NEUROD1-CSNK2A2-PNN pathway is involved in this process.This study was approved by the Animal Ethics Committee of Fujian Medical University,China(approval No.2016-05)on April 18,2016.

Diffusion tensor imaging fiber tracking with reliable tracking orientation and flexible step size

We propose a method of reliable tracking orientation and flexible step size fiber tracking. A new directional strategy was defined to select one optimal tracking orientation from each directional set, which was based on the single-tensor model and the two-tensor model. The directional set of planar voxels contained three tracking directions： two from the two-tensor model and one from the single- tensor model. The directional set of linear voxels contained only one principal vector. In addition, a flexible step size, rather than fixable step sizes, was implemented to improve the accuracy of fiber tracking. We used two sets of human data to assess the performance of our method; one was from a healthy volunteer and the other from a patient with low-grade glioma. Results verified that our method was superior to the single-tensor Fiber Assignment by Continuous Tracking and the two-tensor eXtended Streamline Tractography for showing detailed images of fiber bundles.

PHOTOTHERAPY FOR MILD TO MODERATE ACNE VULGARIS WITH PORTABLE BLUE AND RED LED

In this paper,we studied portable blue and red light-emitting-diode(LED)light sources in phototherapy for mild to moderate acne vulgaris to evaluate the efficacy and tolerance of patients.Patients,randomly divided into blue and red groups,received either blue or red LED phototherapy twice a week for four weeks.After complete treatment,the number of lesions reduced by 71.4% in the blue group,in contrast to 19.5% in the red group.No obvious side effects were observed during and one month after the treatment,except for some mild dryness mentioned by several patients.

Evaluation of fetoplacental oxygenation in a rat model of gestational diabetes mellitus using BOLD-MRI at 7.0-T

Objective:To compare the differences in blood oxygen level-dependent(BOLD)parameters following maternal hyperoxia between normal pregnancy and pregnancy in the rat model of gestational diabetes mellitus(GDM).Methods:GDM was induced by high-fat and sucrose diet(HFS)combined with an intraperitoneal injection of streptozotocin(STZ).On embryonic day 19(E19),the two groups of pregnant rats were imaged using a 7.0-T animal MRI scanner.TurboRARE was initially used to localize the fetoplacental units(FPUs).Next,multiple gradient echo BOLD was performed during the air and oxygen inhalation periods.T2^(*)map was then generated,and the baseline T2^(*)and absolute changes in T2^(*)value(ΔT2^(*),difference between T2^(*)oxy and T2^(*)air)were calculated.Following the MRI scan,the placentas and fetuses were aseptically stripped,weighed,and immunostained.Results:Nine rats were used in this study.After maternal oxygen inhalation,T2^(*)increased significantly in all subjects in both groups.TheΔT2^(*)for the placenta(5.97 vs.7.81 msec;P=0.007)and fetal brain(2.23 vs.3.97 msec;P=0.005)differed significantly between the GDM and control groups.Histochemical detection of placental glycogen content and inflammatory cytokines(IL-6 and TNF-α)showed significantly higher levels in the GDM than in the normal placenta.Conclusions:BOLD-MRI revealed abnormalities in the fetoplacental response to maternal hyperoxygenation in rats with GDM.We believe that this approach can potentially be used to evaluate placental dysfunction and assess the state of the fetus during pregnancy with GDM.

Current status of cerebral glioma surgery in China

The treatment of gliomas is highly individualized. Surgery for gliomas is essentially for histological diagnosis, to alleviate mass effect, and most importantly, to favor longer survival expectancy. During the past two decades, many surgical techniques and adjuvants have been applied to glioma surgery in China, which lead to a rapid development in the field of cerebral glioma surgery. This article broadly and critically reviewed the existing studies on cerebral glioma surgery and to portrait the current status of glioma surgery in China. A literature search was conducted covering major innovative surgical techniques and adjuvants for glioma surgery in China. The following databases were searched： the Pubmed （January 1995 to date）; China Knowledge Resource Integrated Database （January 1995 to date） and VIP Database for Chinese Technical Periodicals （January 1995 to date）. A selection criterion was established to exclude duplicates and irrelevant studies. The outcome measures were extracted from included studies. A total of 3307 articles were initially searched. After excluded by abstracts and full texts, 69 studies conducted in the mainland of China were included and went through further analysis. The philosophy of surgical strategies for cerebral gliomas in China is undergoing tremendous change. Nowadays Chinese neurosurgeons pay more attention to the postoperative neurofunctional status of the patients. The aim of the glioma surgery is not only the more extensive tumor resection but also the maximal safety of intervention. The well balance of longer overall survival and higher quality of life should be judged with respect to each individual patient.

Distribution of bone marrow stem cells in large porous polyester scaffolds

This work examined the optimal syringing depth during in vitro cell loading in order to even cell distribution after syringing a drop of cell suspension in cylinder poly(lactide-co-glycolide) (PLGA) porous scaffolds. The scaffolds of 10 mm height and 10 mm diameter were fabricated via room-temperature compression molding & particulate leaching technique based on spherical porogens. In vitro tests were employed for such examinations: a global observation of a cell-loaded scaffold stained by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) technique and a quantitative measurement of spatial distribution of cells after slicing the cell-loaded scaffolds into layers. It was found that an even distribution of cells was soon achieved only if the initial cell suspension was seeded on the layer that was below the top surface but above the middle of scaffolds. The availability of in vitro osteoblastic differentiation of rat bone marrow stem cells in such a kind of spherical-pore PLGA scaffolds was meanwhile confirmed.

Ethanol disrupts the formation of hypochord and dorsal aorta during the development of embryonic zebrafish

Exposure to ethanol during human embryonic period has severe teratogenic effects on the cardiovascular system.In our study,we demonstrated that ethanol of gradient concentra-tions can interfere with the establishment of circulatory system in embryonic zebrafish.The ef-fective concentration to cause 50%malformations(EC_(50))was 182.5 mmol/L.The ethanol pulse exposure experiment displayed that dome stage during embryogenesis is the sensitive time window to ethanol.It is found that 400 mmol/L ethanol pulse exposure can induce circulatory defects in 43%treated embryos.We ruled out the possibility that ethanol can interfere with the process of hematopoiesis in zebrafish.By employing in situ hybridization with endothelial bio-marker(Flk-1),we revealed that ethanol disrupts the establishment of trunk axial vasculature,but has no effect on cranial vessels.Combined with the results of semi-thin histological sections,the in situ hybridization experiments with arterial and venous biomarkers(ephrinB2,ephB4)sug-gested that ethanol mainly interrupts the development of dorsal aorta while has little effect on axial vein.Further study indicated the negative influence of ethanol on the development of hy-pochord in zebrafish.The consequent lack of vasculogenic factors including Radar and Ang-1 partly explains the defects in formation and integrity of dorsal aorta.These results provide im-portant clues to the study of adverse effects of ethanol on the cardiovascular development in human fetus.

Superficial cervicovaginal myofibroblastoma： report of four cases and literature review

In 2001, Laskin et al firstly described a series of 14 seemly distinctive mesenchymal tumors that occurred exclusively in the superficial lamina propria of the vagina and cervix of middle to old-aged women. They proposed the term ＂superficial cervicovaginal myofibroblastoma （SCVM）＂ to highlight the unique features of this tumor： the superficial subepithelial location and myofibroblastic differentiation of the minor cells. SCVM appears less well recognized with only three additional reports have been documented in the English literatures.24 In this study, we described four new cases of SCVM to further characterize the clinical and pathological features of this rare entity.

Research Progress in the Structure and Functions of Prohibitin

Prohibitin is named due to the negative regulatory role of its gene products in cell proliferation. Prohibitin gene is located at q21 of chromosome 17 in human beings and the protein is found at mitochondria, nucleus and cytoplasm. Due to its size and ring-shaped structure, prohibitin protein defines functional subcompartments in mitochondria. Its subunits, PHB1 and PHB2, suppress cell proliferation as in the protein itself Nevertheless, recent investigation suggests that prohibitin protein enhances cell proliferation as well. It has also been found to suppress cell apoptosis by reducing cytochrome C release via the avoidance of mitochondrial crista remodeling which is facilitated through type 1 optic atrophy protein （OPAl）. Acting as a binding site for ubiquitin, prohibitin protein regulates protein degradation by proteasome. Examples are the degradations of sperm mitochondria in a fertilized ovum or those of an abnormal sperm.

Mutation analysis in a Chinese family with multiple endocrine neoplasia type 1

Background Multiple endocrine neoplasia type 1 （MEN1） by germline mutations of the tumor suppressor gene MEN1. with MEN1. Methods A large Chinese family with MEN1 was collected MEN1 gene were amplified and sequenced. is an autosomal dominant cancer syndrome which is caused This study aimed to identify mutations in a Chinese pedigree All of the coded regions and their adjacent sequences of the Results In this family, a heterozygous cytosine insertion in exon 10 （c.1546_1547insC） inducing a frame shift mutation of MEN1 was found in the proband and the other two suffering members of his family. This mutation was linked to a novel single nucleotide polymorphism （SNP）in intron 3 （IVS3＋18C〉T）. Conclusions The mutation in exon 10 of MEN1 gene might induce development of parathyroid hyperplasia and pituitary adenoma and cosegregate with MEN1 syndrome. The significance of the new found IVS3＋18C〉T of MEN1 needs a further investigation.

Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulation

Retinal pigment epithelial(RPE) is primarily impaired in age-related macular degeneration(AMD), leading to progressive loss of photoreceptors and sometimes choroidal neovascularization(CNV). mTOR has been proposed as a promising therapeutic target, while the usage of its specific inhibitor,rapamycin, was greatly limited. To mediate the mTOR pathway in the retina by a noninvasive approach, we developed novel biomimetic nanocomplexes where rapamycin-loaded nanoparticles were coated with cell membrane derived from macrophages(termed as MRaNPs). Taking advantage of the macrophage-inherited property, intravenous injection of MRaNPs exhibited significantly enhanced accumulation in the CNV lesions, thereby increasing the local concentration of rapamycin. Consequently, MRaNPs effectively downregulated the mTOR pathway and attenuate angiogenesis in the eye. Particularly, MRaNPs also efficiently activated autophagy in the RPE, which was acknowledged to rescue RPE in response to deleterious stimuli. Overall, we design and prepare macrophage-disguised rapamycin nanocarriers and demonstrate the therapeutic advantages of employing biomimetic cell membrane materials for treatment of AMD.

Genome-wide analysis identified 17 new loci influencing intraocular pressure in Chinese population

Intraocular pressure(IOP) is a major risk factor for glaucoma. Genetic determinants of intraocular pressure can provide critical insights into the genetic architecture of glaucoma and, as a result, open new avenues for therapeutic intervention. We performed a genome-wide association study and replication analysis of 8,552 Chinese participants. In the genome-wide association study, we identified 51 loci that surpassed the significance of P<9×10^(-7), and we formally replicated these loci. A combined discovery and replication meta-analysis identified 21 genome-wide loci that surpassed the genome-wide significance of P<5×10^(-8), including 4 previously reported loci: rs145063132(7 p21.2, ETV1/DGKB), rs548030386(7 q31.2, ST7 near CAV1/CAV2), rs7047871(9 p24.2, GLIS3), and rs2472494(9 q31.1, ABCA1/SLC44 A1). Of the 17 newly identified loci, five were reported to have ocular related phenotypes: PTCH2(rs7525308 in 1 p34.1), LRIF1/DRAM2(rs1282146 in 1 p13.3), COLEC11(rs201143466 in 2 p25.3),SPTBN1(rs4514918 in 2 p16.2), and CRK(rs11078446 in 17 p13.3). The genetic loci identified in this study not only increase our understanding of the genes involved in intraocular pressure but also provide important genetic markers to improve future genetic screening and drug discovery for intraocular pressure disorders.