Discovery of EGFR-Targeted Environment-Sensitive fluorescent probes for cell imaging and efficient tumor detection.

Overexpression of human epidermal growth factor receptor (EGFR) plays an important role in several signaling pathways inside and outside the cell, especially in the processes of cell proliferation, differentiation, and death in various cancers. Due to the complexity of the structure and function of EGFR, research on the fluorescence visualization of EGFR protein visualization has proved challenging. One possible strategy for designing a receptor-targeting fluorescent probe with a switching mechanism is to introduce an environment-sensitive fluorophore into the drug ligand. Based on this strategic molecular design, we introduced two environment-sensitive small molecular fluorophores, dansyl chloride (DNS) and nitrobenzoxadiazole (NBD), to replace the morpholine group of gefitinib, achieving a series of fluorescent molecular probes bearing a switching mechanism. The GN probes exhibited prominent environment sensitivity, suggesting good performance as turn-on EGFR-targeting fluorescent ligands. The representative probe GN3 specifically responded to tumor cells overexpressing EGFR, which was validated with live-cell fluorescence imaging and in vivo xenograft tumor imaging. Ligand-induced EGFR phosphorylation in A431 cells was considerably inhibited by probe GN3, demonstrating that this probe still functions as an EGFR inhibitor. Owing to the turn-on response of GN3 to EGFR in tumor cells, and the competitive replacement behavior to the EGFR inhibitor gefitinib, these probes have the potential to be used for fluorescence imaging of cells overexpressing EGFR.

The association of myopia progression with the morphological changes of optic disc and ß-peripapillary atrophy in primary school students.

PURPOSE: To study the association of myopia progression with the morphological changes of optic disc and ß-peripapillary atrophy (ß-PPA) in 8-11 years old primary school students. METHODS: This study was a prospective, school-based investigation. This study included 610 children (1008 eyes) who were continuously observed and had data available from 2016 to 2017 in the Sanhe Cohort Study of the Risk Factors for Myopia (SCSRFM). The children underwent a comprehensive eye examination including measurement of visual acuity, autorefractometry, and posterior segment of the eye. ß-PPA regions and optic disc ovality index were identified and measured on the fundus photographs. RESULTS: The prevalence of myopia was 72.62% (732/1008) in 2016. In myopic children, the prevalence of the vertical ß-PPA, the horizontal ß-PPA, and the oval optic disc were 75.68% (554/732), 75.96% (556/732) and, 11.61% (85/732) respectively. From 2016 to 2017, with the progression of vertical ß-PPA, horizontal ß-PPA, area of ß-PPA, and optic disc ovality index, the myopic diopter and the axial length (AL) were increased. The progression of horizontal ß-PPA was significantly correlated with the progression of myopic diopter and AL (all p < 0.05). The analysis on the distribution of progression rate of parameters in different groups found that the progression rate of horizontal ß-PPA, area of ß-PPA, and optic disc ovality index increased with the increase of the progression of diopter and AL. The progression of horizontal ß-PPA, area of ß-PPA, optic disc ovality index, and diopter in girls were greater than that in boys, and the progression of optic disc ovality index and diopter had a statistical significance (all p < 0.05). CONCLUSIONS: The 1-year follow-up study of the third-grade primary school students showed that with the progression of myopia and the growth of AL, ß-PPA and optic disc ovality index also changed. There was a positive correlation between the change of ß-PPA and optic disc ovality index and the progression of myopia diopter and AL.

The effect of retaining intact posterior capsule in congenital cataract surgery in children aged 4-8 years.

BACKGROUND: The present study sought to observe the effect of retaining intact posterior capsule in congenital cataract surgery in children aged 4-8 years. METHODS: This is a retrospective case control study. Seventy-seven children (130 eyes) aged from 4 to 8 years who underwent cataract surgery were divided into two groups. In Group A, 50 eyes underwent phacoemulsification, intraocular lens implantation and posterior capsule capsulotomy combined with anterior vitrectomy. In Group B, 80 eyes underwent cataract phacoemulsification and intraocular lens implantation. The postoperative visual acuity and the rate of complications were compared. RESULTS: In all patients, cataract surgeries were performed evenly without intraoperative complications. The follow-up time ranged from 6 months to 42 months. No apparent visual axis opacity was detected in group A during the follow-up. By the last visit, apparent visual axis opacity was detected in 31 eyes (38.75%) in group B. Among them, 9 eyes (29.03%) with mild posterior capsule opacification (PCO) were treated with Nd:YAG laser, 3 eyes (9.68%) with thick proliferative membranes were treated with posterior capsule capsulotomy combined with anterior vitrectomy and proliferative membranes in 19 eyes (61.29%) were completely aspired and the posterior capsule was retained. During follow-up, only 2 (6.45%) eyes had PCO recurrence and were treated with Nd:YAG laser. The visual acuity was significantly higher than that before surgery in all patients. CONCLUSIONS: For older children, the incidence of PCO will be low even if intact posterior capsule is retained. Either Nd:YAG laser or surgical treatment for PCO will be able to maintain good vision.

Effect of lens capsular tension ring on preventing capsular contraction syndrome in the surgery of retinitis pigmentosa combined with cataract: Retrospective case series.

PURPOSE: To observe the effect of phacoemulsification and intraocular lens (IOL) implantation with or without lens capsular tension ring (CTR) on retinitis pigmentosa (RP) combined with cataract patients. DESIGN: Retrospective cases series study. METHODS: Sixty-three cases (84 eyes) of RP with cataract were collected, including 30 males and 33 females. Phacoemulsification with 3.0 mm clear corneal incision was performed in all the patients. IOL and CTR implantation were performed in 44 eyes, and IOL implantation alone was performed in 40 eyes. All cases were followed up at 1 day, 1 week and 1, 3, 6,12 months after the surgery to compare the best-corrected visual acuity (BCVA), intraocular pressure (IOP), corneal endothelial cell count (ECC) and complications before and after the surgery. RESULTS: All surgery were successfully completed by the same physician, and IOL and CTR were all implanted in capsule without complications. The BCVA at 6 months after surgery was 0.91 ± 0.88 LogMAR, showing an improvement compared with the BCVA(1.3 ± 0.7LogMAR) before surgery and there was a statistically significant difference (P = .003). Four cases of capsule contraction syndrome (CCS) occurred in no CTR implantation group and there was no CCS in CTR group. There was a statistically significant difference in the incidence of CCS between two groups (P = .047). CONCLUSIONS: Phacoemulsification for RP combined with cataract is safe and reliable, and CTR implantation is conducive to reducing the complications caused by capsule contraction.

The expression of cytokines in aqueous humor of high myopic patients with cataracts.

Purpose: To analyze the expression of 440 human cytokines in aqueous humor of high myopic patients with cataracts. Methods: Eighty-five patients with cataracts were recruited in this study. In the screening stage, the RayBio G-Series Human Cytokine Antibody Array 440 was used to assay the aqueous humor samples collected from nine high myopic patients with cataracts and eight non-myopic patients with cataracts right before the surgery. The array was further used for verification of the screened cytokines, with aqueous humor samples obtained from 34 eyes of high myopic patients with cataracts and 34 eyes of non-myopic patients with cataracts. Results: Compared with the non-myopic patients with cataracts, the expression levels of decorin, receptor activator of NF-kB (RANK), angiopoietin-1 (ANG-1), C-X-C motif ligand 16 (CXCL16), ß-inducible gene-h3 (bIG-H3), insulin-like growth factor-binding protein 2 (IGFBP-2), and interleukin-17B (IL-17B) were statistically significantly higher in high myopic patients with cataracts (all p<0.000114). The matrix metalloproteinase-2 (MMP-2) level also increased in the aqueous humor of high myopic patients with cataracts (p = 0.0034). The concentrations of ANG-1 and MMP-2 were also increased in the aqueous humor of the confirmatory stage (all p<0.05). Conclusions: In this study, numerous cytokines in aqueous humor were detected in high myopic patients with cataracts and non-myopic patients with cataracts, and it was confirmed that the MMP-2 level in the aqueous humor of patients with high myopia was statistically significantly increased. Further verification also revealed the elevation of ANG-1 in the aqueous humor of high myopic patients with cataracts, which suggests that ANG-1 may be related to the pathogenesis of high myopia.

The high expression of the pain-related inflammatory factors in the eyes of cataract patients infected with hepatitis B virus.

In cataract surgery, it is often found that patients infected hepatitis B virus (HBV) are likely to suffer from more pain than other patients. In order to assess the inflammation status of the aqueous humor in the eyes of cataract patients infected with HBV. RayBio Human Inflammation Array was used to assay aqueous humor samples collected from 14 eyes of patients infected with HBV and 14 eyes of cataract patients without HBV infection (the controls) during the cataract surgery. RayBio Human Quantibody Cutom Array was adopted for the validation of the screened cytokines, with aqueous humor samples collected from 40 eyes of patients infected with HBV and 40 eyes of the controls. A pain questionnaire survey about the surgery was conducted in all patients after operation. The results of questionnaire showed that patients infected with HBV were more likely to have pain during operation. The Human Inflammation Array revealed that the expression levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor α (TNF-α) and tumor necrosis factor ß (TNF-ß) were very high in HBV infected patients and IL-1ra was much lower in patients infected with HBV (all, P < 0.05). In validation, the Human Quantibody Cutom Array revealed that the expression levels of MCP-1 and TNF-α were high in HBV infected patients with significant difference (all P < 0.05). These results revealed that pain-related inflammatory factors MCP-1 and TNF-α were increased in aqueous humor of cataract patients infected with HBV, which indicates that patients infected with HBV may be more prone to intraoperative pain.

A Versatile Enantioselective Catalytic Cyclopropanation-Rearrangement Approach to the Divergent Construction of Chiral Spiroaminals and Fused Bicyclic Acetals.

A highly enantioselective synthesis of various chiral heterobicyclic molecules including spiroaminals and fused bicyclic acetals has been developed via a chiral copper catalyzed cyclopropanation-rearrangement (CP-RA) approach under mild reaction conditions. Remarkably, the asymmetric CP-RA for exocyclic vinyl substrates without a pro-stereogenic carbon at the ß-position has been realized for the first time and a broad substrate scope with excellent results (33 examples; 34-99 % yields; >95/5 dr and 91-99 % ee) has been achieved. An application of a successive enantioselective CP-RA approach was also described, providing a concise access to complex chiral heteropolycycles.

Effect of transcutaneous electrical stimulation treatment on lower urinary tract symptoms after class III radical hysterectomy in cervical cancer patients: study protocol for a multicentre, randomized controlled trial.

BACKGROUND: Class III radical hysterectomy (RH III)_plus pelvic lymphadenectomy is the standard surgery for early stage cervical cancer (CC) patients, the 5 year survival rate is about 90%, but pelvic floor disorders especially bladder dysfunction are common due to damaged vessels and nerve fibers following surgery. Transcutaneous electrical stimulation (TENS) treatment has been used to treat bladder disorders for many years, but its effect on cervical cancer patients, the best treatment time point and stimulated protocol, had never been assessed. The aim of this study is to investigate the efficacy of TENS treatment on lower urinary tract symptoms (LUTS) after RH III in CC patients. METHODS/DESIGN: The study will be conducted as a clinical, multicentre, randomised controlled trial with balanced randomisation (1:1). The planned sample size is 208 participants (at 1:1 ratio, 104 subjects in each group). At 5-7 days after RH III, patients are screened according to operative and pathological findings. Enrolled participants are randomised into an intervention group (TENS plus conventional clinical care) or control group (conventional clinical care), with stratification by menopausal status (menopause vs. non-menopause) and surgical modality (laparoscopic RH or abdominal RH). Participants in both groups will be followed up at 14 days, 21 days, 28 days, 3 months, 6 months, 12 months, 18 months and 24 months after surgery. The primary endpoint is improvement rate of urination function which is defined as recovery (residual urine ≤50 ml) or improvement (residual urine 50-100 ml). Secondary endpoints include urodynamic parameter, urinary incontinence, anorectal function, pelvic function, quality of life (QOL), disease-free survival and adverse events. Primary endpoint analyses will be carried out by Cochran-Mantel-Haenszel tests taking into center effect. DISCUSSION: To our knowledge this is the first trial to investigate the effect of TENS treatment on bladder function recovery after RH III among CC patients. This study will provide new information on TENS efficacy for bladder function recovery. Once confirmed, it may help to provide a new, non-invisive treatment for those postoperative CC patients with poor pelvic function, which would help improve their quality of life. TRIAL REGISTRATION: The study is registered to Clinical Trials.gov ( NCT02492542 ) on June 25, 2015.

Side arm strategy for catalyst design: modifying bisoxazolines for remote control of enantioselection and related.

In asymmetric catalysis, the remote control of enantioselection is usually difficult due to the long distance communication between the chiral center of the catalyst and the reactive site of the substrate. The development of efficient and highly enantioselective catalysts for such reactions is of great importance and highly desirable. The stereocontrol over an asymmetric reaction is a delicate process (ca. 3.0 kcal/mol difference in transition states can lead to >99/1 enantiomeric selectivity at room temperature), it therefore requires fine-tuning on the electronic nature of the central metal together with a precisely created cavity to accommodate the substrates and reagents. We envision that a solution is the design of new catalysts by finding an easy and efficient way to tune the electronic properties, the chiral space, and the shape of the catalytic site. Since an extra coordination group in the organometallic complex could not only alter the microenvironment around the metal center in a three-dimensional manner but also tune the electronic properties of the metal center, about 10 years ago, we introduced a side arm strategy for ligand/catalyst design. This Account describes our efforts toward this goal. Based on this side arm strategy, we have developed two series of ligands based on the bisoxazoline framework; namely, trisoxazoline (TOX) ligands and side armed bisoxazoline (SaBOX). The "side arms" are shown to play multiple roles in different cases, for example, as a ligating group, a steric group, or a directing group, which are dependent on the metal and the functionality at the side arm. Metal catalysts based on these ligands have proven to be highly efficient for a number of asymmetric transformations, including Friedel-Crafts reaction, Kinugasa reaction, Nazarov reaction, 1,2-Stevens rearrangement, Cannizzaro reaction, and cyclopropanation. In comparison with the parent BOX ligands, the metal catalysts based on these TOX and SaBOX ligands usually exhibit higher efficiency and diastereo- and enantioselectivity with better impurity tolerance and stability. Moreover, in several TOX-metal complex catalyzed reactions such as Friedel-Crafts reaction and [3 + 2] cycloaddition, stereoselectivity could be switched based on reaction conditions. These ligands were particularly prominent in the remote controls of enantioselection such as the conjugate additions to alkylidene malonates and ring-opening/cyclization cascades of cyclopropanes, for which high stereoselectivity is usually difficult to achieve due to the poor chiral communication. The works by us and other groups have demonstrated that the side arm strategy can be employed as a general principle for ligand and catalyst design and should not be limited to the BOX scaffolds and the reactions described in this Account. Wide application of the new strategy in organometallic homogeneous catalysis can be anticipated.

Circular olefin copolymers made de novo from ethylene and α-olefins.

Ethylene/α-olefin copolymers are produced in huge scale and widely used, but their after-use disposal has caused plastic pollution problems. Their chemical inertness made chemical re/upcycling difficult. Ideally, PE materials should be made de novo to have a circular closed-loop lifecycle. However, synthesis of circular ethylene/α-olefin copolymers, including high-volume, linear low-density PE as well as high-value olefin elastomers and block copolymers, presents a particular challenge due to difficulties in introducing branches while simultaneously installing chemical recyclability and directly using industrial ethylene and α-olefin feedstocks. Here we show that coupling of industrial coordination copolymerization of ethylene and α-olefins with a designed functionalized chain-transfer agent, followed by modular assembly of the resulting AB telechelic polyolefin building blocks by polycondensation, affords a series of ester-linked PE-based copolymers. These new materials not only retain thermomechanical properties of PE-based materials but also exhibit full chemical circularity via simple transesterification and markedly enhanced adhesion to polar surfaces.

A highly efficient and enantioselective intramolecular Cannizzaro reaction under TOX/Cu(II) catalysis.

An asymmetric intramolecular Cannizzaro reaction of aryl and alkyl glyoxals with alcohols has been realized with an unprecedented high level of enantioselectivity, on the basis of a newly developed congested TOX ligand and a gradual liberation protocol of active glyoxals from glyoxal monohydrates. Preliminary results suggested a mechanism of enantioselective addition of alcohols to glyoxals contributing most to the stereoselectivity, other than by the dynamic kinetic resolution of hemiacetal intermediates.

Water as an activator for palladium(II)-catalyzed olefin polymerization.

By a reasonable combination of the Wacker reaction and olefin polymerization processes, water proves to be an excellent activator for the palladium(II)-catalyzed polymerization of ethylene and it provides a safe, environmental-friendly and handy initiator for olefin polymerization. The activity of the olefin polymerization is comparable to reactions catalyzed by the corresponding alkylated cationic palladium complexes.

[Preliminary study on pelvic organ prolapse treated by using small intestinal submucosa mesh].

OBJECTIVE: To study clinical efficacy of porcine-derived small intestinal submucosa (Surgisis) in treatment of pelvic organ prolapse (POP). METHODS: From Mar. 2012 to Mar. 2013, 15 patients with POP at more than III of POP quantitation (POP-Q) staging system undergoing pelvic reconstructive surgery with Surgisis in Peking University People's Hospital. The mean age was 59 years old (39-82). The variable site of POP-Q staging system was compared between preoperative and postoperative status among those patients.Quality of life questionnaire of pelvic floor impact questionnaire (PFIQ-7), pelvic floor distress inventory short form (PFDI-20) and PISQ-31 were studied to evaluate subjective satisfaction, recurrence and the quality of life's improvement. RESULTS: All patients were followed up at mean of 9.9 months (3-15 months), the mean time of surgery was 96 mins (65-120 mins), the mean blood loss was 159 ml (50-500 ml).No infection and erosion was observed on those patients. The rate of subjective satisfaction was 14/15, the recurrence rate of prolapse was 2/15.Scoring system of PFDI-20 was from 87 (56-124) at operative status to 30 (22-48) at postoperative status. PFIQ-20 was from 129 (85-158) at preoperative status to 24 (18-48) at postoperative status. PISQ-31 was from 48 (32-55) at preoperative status to 79 (66-89) at postoperative status, which all reached statistical difference (all P < 0.05). Total 9 patients obtained satisfactory sexual life. CONCLUSIONS: The short-term clinical effect of pelvic reconstructive surgery with Surgisis was satisfied, quality of life and sexual life was improved, and less complication were observed. However, long-term clinical effect on patients should be warranted to follow up.

Multicenter evaluation of a simple and sensitive nucleic acid self-testing for SARS-CoV-2.

A rapid and accurate COVID-19 diagnosis is a prerequisite for blocking the source of infection as soon as possible and taking the appropriate medical action. Herein, we developed GeneClick, a device for nucleic acid self-testing of SARS-CoV-2, consisting of three modules: a sampling kit, a microfluidic chip-based disposable cartridge, and an amplification reader. In addition, we evaluated the clinical performance of GeneClick using 2162 nasal swabs collected at three medical institutions, using three commercial RT-qPCR kits and an antigen self-test as references. Compared to RT-qPCR, the sensitivity and specificity of the GeneClick assay were 97.93% and 99.72%, respectively, with a kappa value of 0.979 (P â€‹< â€‹0.01). Of the 2162 samples, 2076 were also tested for SARS-CoV-2 antigens. Among the 314 positive samples identified by GeneClick assay, 63 samples were undetected by antigen tests. Overall, the GeneClick nucleic acid self-test demonstrated higher accuracy than the antigen-based detection. Based on the additional features, including simple operation, affordable price, portable device, and reliability of smartphone APP-driven sampling and result reporting, GeneClick offers a powerful tool for field-based SARS-CoV-2 detection in primary healthcare institutions or at-home use.

Side-arm-promoted highly enantioselective ring-opening reactions and kinetic resolution of donor-acceptor cyclopropanes with amines.

A Ni-catalyzed asymmetric ring-opening reaction of 2-substituted cyclopropane-1,1-dicarboxylates with aliphatic amines has been accomplished using the chiral indane-trisoxazoline (In-TOX) ligand. This highly enantioselective reaction provides an efficient approach to a variety of chiral γ-substituted γ-amino acid derivatives, which are readily transformed into multifunctionalized piperidines and γ-lactams. The single-crystal X-ray structure of the TOX-Ni complex is provided, and the role of the side arm in the chiral ligand is discussed.

Highly diastereoselective construction of fused carbocycles from cyclopropane-1,1-dicarboxylates and cyclic enol silyl ethers: scope, mechanism, and origin of diastereoselectivity.

Cyclopropane rings true: By selecting the appropriate substituents on the ester and silyl groups, fused cyclopentane derivatives with multiple contiguous stereocenters can be synthesized with excellent diastereoselectivity through Cu(II)/bisoxazoline-catalyzed intermolecular [3+2] cycloaddition reactions of cyclopropane-1,1-dicarboxylates and cyclic enol silyl ethers (see scheme).

[Value of CA(125) in the prediction of optimal interval debulking surgery and its prognosis in patients with epithelial ovarian cancer].

OBJECTIVE: To investigate the changes of CA(125) between primary cytoreductive surgery and interval debulking surgery for prediction the rate of optimal interval cytoreductive surgery and prediction the recurrence and the prognosis in patients with epithelial ovarian cancer. METHODS: A total of 39 cases with suboptimal primary cytoreductive surgery admitted from Jan. 1996 to Jan. 2009 were retrospectively analyzed. The median age of patients was 56 years (range: 41 - 68 years). Based on the changes in CA(125) level between primary cytoreductive surgery and interval debulking surgery, all cases were divided into four groups, group A (CA(125) reduced to normal after primary cytoreductive surgery, n = 6), group B (CA(125) reduced to normal after 1-2 cycles of chemotherapy, n = 11), group C (CA(125) reduced to normal after 3-4 cycles of chemotherapy, n = 14), and group D (CA(125) did not reduced to normal after the chemotherapy, n = 8), and all received platinum-based chemotherapy. The response to chemotherapy evaluated by pathological examination versus CA(125) level, and recurrence and prognoses were also analyzed. RESULTS: (1) The rate of optimal interval cytoreductive surgery in group A, B, C and D were 6/6, 8/11, 9/14 and 2/8 respectively, in which there were statistically different between group A or B and group D (P < 0.05). (2) The clinical benefit rates evaluated by the pathological examination in group A, B, C and D were 4/6, 4/11, 5/14 and 0, respectively and there were statistically different between group A and group D (P = 0.030). (3) There was significant difference in the recurrence rate between group A and group D (3/6 vs. 8/8, P = 0.024), while there were not significant differences between group B or C and group D (all P > 0.05). The rate of drug-resistant recurrence in group A, B, C and D were 1/6, 3/11, 5/14 and 7/8, respectively, in which there were significant differences between group A, B or C and group D (all P < 0.05). (4) The median progression-free survival (PFS) for patients in group A, B, C and D were 32, 10, 18 and 3 months, respectively, in which there were significant differences in the PFS between group A, B or C and group D (P = 0.012, P = 0.003, P = 0.032). The median overall survival (OS) were 44, 45, 44 and 16 months, respectively. There were significant differences in the OS between group A, B or C and group D (P = 0.022, P = 0.004, P = 0.000). CONCLUSION: The change of CA(125) between primary cytoreductive surgery and interval debulking surgery may be predict the recurrence type and the prognosis in patients with epithelial ovarian cancer.

Histiocytoid giant cellulitis-like Sweet syndrome at the site of sternal aspiration: A case report and review of literature.

BACKGROUND: Giant cellulitis-like Sweet syndrome (SS) is a rare subtype of SS, and reports of the combined histiocytoid type of pathology are scarce. Here, we report a case of SS with distinctive clinical presentations and which was difficult to distinguish from cellulitis. By sharing this case and a discussion of the related literature in detail, we aim to provide clinicians with new insights into the characteristics of histiocytoid giant cellulitis-like (HGC)-SS and the pathogenesis of SS. CASE SUMMARY: A 52-year-old male was admitted after experiencing progressive fatigue for 1 mo and tongue swelling with pain for 1 d. He was diagnosed with myelodysplastic syndrome (MDS) and angioneurotic edema of the tongue and floor of the mouth. However, 7 d after examination by sternal aspiration, a violaceous, tender, and swollen nodule developed at the site, with poorly demarcated erythema of the surrounding skin. Considering his profile of risk factors, the diagnosis of cellulitis was made and he was administered broad-spectrum antibiotics. When the lesion continued to worsen and he developed chills and fever, pathogenic and dermatopathological examination led to the diagnosis of HGC-SS. Treatment with prednisone led to the fever being relieved within 24 h and the skin lesion being resolved within 1 wk. The patient refused intensive treatment and was instead given thalidomide, erythropoietin, stanozolol, and supportive care. The prednisone was gradually tapered, with no signs of recurrence, but he died 2 mo later of severe pneumonia. CONCLUSION: HGC-SS demonstrates unique manifestation. SS and leukemia cutis share cytological origin. Myelofibrosis and SS are adverse prognostic factors for MDS.

Dimeric-(-)-epigallocatechin-3-gallate inhibits the proliferation of lung cancer cells by inhibiting the EGFR signaling pathway.

Non-small cell lung cancer (NSCLC) is one of the most general malignant tumors. The overexpression of epidermal growth factor receptor (EGFR) is a common marker in NSCLC, and it plays an important role in the proliferation, invasion, and metastasis of cancer cells. At present, drugs developed with EGFR as a target suffer from drug resistance, so it is necessary to study new compounds for the treatment of NSCLC. The active substance in green tea is EGCG, which has anti-cancer effects. In this study, we synthesized dimeric-(-)-epigallocatechin-3-gallate (prodelphinidin B-4-3,3‴-di-O-gallate, PBOG), and explored the effect of PBOG on lung cancer cells. PBOG can inhibit the proliferation and migration of NCI-H1975 cells, promote cell apoptosis, and inhibit cell cycle progression. In addition, PBOG can bind to the EGFR ectodomain protein and change the secondary structure of the protein. At the same time, PBOG decreases the expression of EGFR and downstream protein phosphorylation. Animal experiments confirmed that PBOG can inhibit tumor growth by inhibiting EGFR phosphorylation. Collectively, our study results show that PBOG may induce a decrease in intracellular phosphorylated EGFR expression by binding to the EGFR ectodomain protein, thereby inducing apoptosis and inhibiting cell cycle progression, thus providing a new strategy to treat lung cancer.