Health starts with maternal and child safety:maternal and child health of Shanghai under the Suitable Public Health System / 上海预防医学

The maternal and child health (MCH) is of great significance to human health.Focusing on the goal of "improving the quality of the birth population, reducing maternal mortality, infant mortality, the incidence of birth defects, and the sex ratio of the birth population", Shanghai has always attached importance to MCH and achieved remarkable results, highly praised by then Secretary-General Ban Ki-moon.In 2018, the average life expectancy of women (86.08 years), maternal mortality rate (1.18/105) and infant mortality rate (3.5‰) in Shanghai, the main indicators of MCH, have reached the most advanced level in the world.An evaluation on MCH system of Shanghai has been conducted with "Evaluation Criteria for Suitable Public Health System", which was developed by Research Institute of Health Development Strategies, Fudan University and Collaborative Innovation Center of Health Risks Governance.MCH of Shanghai ranked first among 10 representative global cities(885.0 points and 937.1 points).Reviewing the development of MCH in Shanghai, five experiences were summarized.Firstly, the government was as the lead to continuously improve the MCH system (Government-led score of 836.6 points).Secondly, service network was continually improved as "five networks, one channel and two priorities" (Organizational soundness score of 1 000.0).Thirdly, focusing on overall coordination and continually taking advantages of high-quality medical resources (Coordination score of 613.4 and 667.6).Fourthly, emphasizing sustainable development and continuing to optimize resource investment (Financial suitability score of 756.3 and Personnel competence score of 677.6).Fifthly, adhering to construction of regulations and continuous improvement of MCH management and service capabilities (Regulation content integrity score of 884.1).MCH system in Shanghai has explored a development path suitable for the city itself.Next step, if more efforts can be made to "clarify the responsibilities of relevant departments and ensure their implementation", Shanghai's MCH system is expected to become a role model for global cities in 4-5 years.

Health starts with maternal and child safety:maternal and child health of Shanghai under the Suitable Public Health System / 上海预防医学

The maternal and child health (MCH) is of great significance to human health.Focusing on the goal of "improving the quality of the birth population, reducing maternal mortality, infant mortality, the incidence of birth defects, and the sex ratio of the birth population", Shanghai has always attached importance to MCH and achieved remarkable results, highly praised by then Secretary-General Ban Ki-moon.In 2018, the average life expectancy of women (86.08 years), maternal mortality rate (1.18/105) and infant mortality rate (3.5‰) in Shanghai, the main indicators of MCH, have reached the most advanced level in the world.An evaluation on MCH system of Shanghai has been conducted with "Evaluation Criteria for Suitable Public Health System", which was developed by Research Institute of Health Development Strategies, Fudan University and Collaborative Innovation Center of Health Risks Governance.MCH of Shanghai ranked first among 10 representative global cities(885.0 points and 937.1 points).Reviewing the development of MCH in Shanghai, five experiences were summarized.Firstly, the government was as the lead to continuously improve the MCH system (Government-led score of 836.6 points).Secondly, service network was continually improved as "five networks, one channel and two priorities" (Organizational soundness score of 1 000.0).Thirdly, focusing on overall coordination and continually taking advantages of high-quality medical resources (Coordination score of 613.4 and 667.6).Fourthly, emphasizing sustainable development and continuing to optimize resource investment (Financial suitability score of 756.3 and Personnel competence score of 677.6).Fifthly, adhering to construction of regulations and continuous improvement of MCH management and service capabilities (Regulation content integrity score of 884.1).MCH system in Shanghai has explored a development path suitable for the city itself.Next step, if more efforts can be made to "clarify the responsibilities of relevant departments and ensure their implementation", Shanghai's MCH system is expected to become a role model for global cities in 4-5 years.

Correction to: CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation.

Following publication of their article "CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation", the authors reported an error in Fig.6b. α-Tubulin image of rCCN2 treatment  (upper panel in CL1-5) only showed eight lanes, when there should be nine.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) promotes EGF receptor signaling of oral squamous cell carcinoma metastasis via the complex N-glycosylation.

Aberrant protein glycosylation could be a distinct surface-marker of cancer cells that influences cancer progression and metastasis because glycosylation can regulate membrane protein folding which alters receptor activation and changes epitope exposure for antibody (Ab) recognition. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a glycophosphoinositol-anchored protein, is a heavily glycosylated tumor antigen. However, the clinical significance and biological effect of CEACAM6 glycosylation has not been addressed in cancers. We recently developed an anti-CEACAM6 Ab (TMU) from an immune llama library which can be engineered to a single-domain (sd)Ab or a heavy-chain (HC)Ab. The TMU HCAb specifically recognized glycosylated CEACAM6 compared to the conventional antibodies. Using the TMU HCAb, we found that glycosylated CEACAM6 was a tumor marker associated with recurrence in early-stage OSCC (oral squamous cell carcinoma) patients. CEACAM6 promoted OSCC cell invasion, migration, cytoskeletal rearrangement, and metastasis via interaction with epidermal growth factor (EGF) receptor (EGFR) and enhancing EGFR activation, clustering and intracellular signaling cascades. These functions were modulated by N-acetylglucosaminyltransferase 5 (MGAT5) which mediated N-glycosylation at Asn256 (N256) of CEACAM6. Finally, the TMU sdAb and HCAb treatment inhibited the migration, invasion and EGF-induced signaling in CEACAM6-overexpressing cells. In conclusion, the complex N-glycosylation of CEACAM6 is critical for EGFR signaling of OSCC invasion and metastasis. Targeting glycosylated CEACAM6 with the TMU sdAb or TMU HCAb could be a feasible therapy for OSCC.

Outcomes of Highly Sensitized Patients Undergoing Simultaneous Liver and Kidney Transplantation: A Single-Center Experience With Desensitization.

BACKGROUND: Preformed donor-specific human leukocyte antigen antibodies (DSAs) in patients undergoing simultaneous liver and kidney transplantation (SLKT) are an independent risk factor for poorer patient and renal allograft survival. The outcomes of patients highly sensitized (HS) against HLA antigens undergoing SLKT and select HS SLKT recipients undergoing desensitization at a high-volume desensitization center were investigated. METHODS: Seventy-five patients undergoing SLKT at a high-volume desensitization center between January 1, 2001, and December 31, 2015, were retrospectively reviewed. HS patients were defined by panel-reactive antibody (PRA) >30% (n = 17 patients), 11 of whom received pre- or perioperative desensitization with high-dose intravenous immunoglobulin (IVIG) ± rituximab. RESULTS: HS patients had significantly higher class I and class II PRA (class I = 41.3% ± 40.0% vs 2.5% ± 6.3%; class II = 45.7% ± 36.4% vs 1.0% ± 2.9%; P < .001), were more likely to be female (P = .05), and more likely to have had a prior transplant (P = .03). HS patients demonstrated greater susceptibility to renal cell-mediated rejection (CMR) (23.5% vs 5.2%, P = .02) compared to nonsensitized patients. Higher renal antibody-mediated rejection (ABMR) was also observed in HS patients, 11.8% vs 3.4%, but did not reach significance (P = .18). Desensitization in select HS SLKT patients was well tolerated but did not improve patient and allograft survival or significantly curtail rejection. CONCLUSION: HS SLKT recipients demonstrated increased allograft rejection, particularly CMR, but patient and graft survival were not impacted in the first year post-transplant. Select HS SLKT patients tolerated desensitization with high-dose IVIG ± rituximab and may have received additional immunoprotection against ABMR but survival was not affected.

Successful Treatment of Mitochondrial Toxicity in an HIV-Positive Patient After Liver Transplantation.

Liver transplantation in patients infected with the human immunodeficiency virus (HIV) has been increasingly performed with reasonable outcomes; however, medical management of both immunosuppression and antiretroviral therapy can be challenging owing to drug toxicities and interactions. Nucleoside reverse transcriptase inhibitors (NRTIs), a common backbone of highly active antiretroviral therapy (HAART), were the first class of effective antiretroviral drugs developed. NRTIs are commonly used for posttransplant HAART therapy and have a rare but fatal complication of mitochondrial toxicity, manifesting as severe lactic acidosis, hepatic steatosis, and lipoatrophy. Herein, we have reported on the first known successful treatment of severe mitochondrial toxicity secondary to NRTIs in an HIV-infected transplant recipient.

CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation.

CCN family protein 2 (CCN2), also known as connective tissue growth factor, is a secreting protein that modulates multiple cellular events. We previously demonstrated the metastasis-suppressive effect of CCN2 in lung cancer cells. In this study, we investigate the role of CCN2 in anoikis, a form of programmed cell death that is critical in suppressing cancer metastasis. CCN2 binds to the epidermal growth factor receptor (EGFR) and triggers ubiquitination by inhibiting the formation of the ß-pix/Cbl complex, resulting in the degradation of EGFR. Binding of CCN2 to EGFR suppresses the phosphorylation of c-Src and extracellular signal-regulated kinase but increases the expression of death-associated protein kinase, which leads to anoikis. Overall, our findings provide evidence validating the use of CCN2 as an anti-metastatic therapy in lung cancer patients, and prospect a potential therapeutic synergy between CCN2 and the anti-EGFR antibody for the treatment of lung cancer.

SCUBE3 is an endogenous TGF-ß receptor ligand and regulates the epithelial-mesenchymal transition in lung cancer.

Signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) is a secreted glycoprotein that is overexpressed in lung cancer tumor tissues and is correlated with the invasive ability in a lung cancer cell line model. These observations suggest that SCUBE3 may have a role in lung cancer progression. By exogenous SCUBE3 treatment or knockdown of SCUBE3 expression, we found that SCUBE3 could promote lung cancer cell mobility and invasiveness. Knockdown of SCUBE3 expression also suppressed tumorigenesis and cancer metastasis in vivo. The secreted SCUBE3 proteins were cleaved by gelatinases (matrix metalloprotease-2 (MMP-2) and MMP-9) in media to release two major fragments: the N-terminal epidermal growth factor-like repeats and the C-terminal complement proteins C1r/C1s, Uegf and Bmp1 (CUB) domain. Both the purified SCUBE3 protein and the C-terminal CUB domain fragment, bound to transforming growth factor-ß (TGF-ß) type II receptor through the C-terminal CUB domain, activated TGF-ß signaling and triggered the epithelial-mesenchymal transition (EMT). This process includes the induction of Smad2/3 phosphorylation, the increase of Smad2/3 transcriptional activity and the upregulation of the expression of target genes involved in EMT and cancer progression (such as TGF-ß1, MMP-2, MMP-9, plasminogen activator inhibitor type-1, vascular endothelial growth factor, Snail and Slug), thus promoting cancer cell mobility and invasion. In conclusion, in lung cancer cells, SCUBE3 could serve as an endogenous autocrine and paracrine ligand of TGF-ß type II receptor, which could regulate TGF-ß receptor signaling and modulate EMT and cancer progression.

Kimura disease: review of the literature.

Kimura disease (KD) is a rare, chronic inflammatory disease of unknown cause and is characterized by painless s.c. swellings and lymphadenopathy commonly affecting the head and neck region. Much therapeutics has been used to treat KD, but is not satisfactory because of frequent relapse. Imatinib has been reported previously to be useful for treatment of hypereosinophilic syndrome and may work by selectively blocking protein-tyrosine kinases, such as platelet-derived growth factor receptor, and c-Kit. We carried out immunohistochemical examination of platelet-derived growth factor receptor-alpha and c-Kit in tissues from patients with KD. The results were positive and suggested that Imatinib might be an effective drug for the treatment of the disease. We have also briefly reviewed the epidemiology, aetiology, clinical manifestations, laboratory and pathological examinations, differential diagnoses, treatment and prognosis of KD in this manuscript.

STM studies of the electronic structure of vortex cores in Bi(2)Sr(2)CaCu(2)O(8+delta)

We report on low temperature scanning tunneling microscopy (STM) studies of the electronic structure of vortex cores in Bi 2Sr 2CaCu 2O (8+delta). At the vortex core center, an enhanced density of states is observed at energies near Omega = +/-7 meV. Spectroscopic imaging at these energies reveals an exponential decay of these "core states" with a decay length of 22+/-3 A. The fourfold symmetry sometimes predicted for d-wave vortices is not seen in spectroscopic vortex images. A locally nodeless order parameter induced by the magnetic field may be consistent with these measurements.

Imaging the effects of individual zinc impurity atoms on superconductivity in Bi2Sr2CaCu2O8+delta

Although the crystal structures of the copper oxide high-temperature superconductors are complex and diverse, they all contain some crystal planes consisting of only copper and oxygen atoms in a square lattice: superconductivity is believed to originate from strongly interacting electrons in these CuO2 planes. Substituting a single impurity atom for a copper atom strongly perturbs the surrounding electronic environment and can therefore be used to probe high-temperature superconductivity at the atomic scale. This has provided the motivation for several experimental and theoretical studies. Scanning tunnelling microscopy (STM) is an ideal technique for the study of such effects at the atomic scale, as it has been used very successfully to probe individual impurity atoms in several other systems. Here we use STM to investigate the effects of individual zinc impurity atoms in the high-temperature superconductor Bi2Sr2CaCu2O8+delta. We find intense quasiparticle scattering resonances at the Zn sites, coincident with strong suppression of superconductivity within approximately 15 A of the scattering sites. Imaging of the spatial dependence of the quasiparticle density of states in the vicinity of the impurity atoms reveals the long-sought four-fold symmetric quasiparticle 'cloud' aligned with the nodes of the d-wave superconducting gap which is believed to characterize superconductivity in these materials.

Atomic-scale quasi-particle scattering resonances in Bi2Sr2CaCu2O8+delta

Low-temperature scanning tunneling spectroscopy of the high transition temperature (high-Tc) cuprate Bi2Sr2CaCu2O8+delta reveals the existence of large numbers of identical regions with diameters of about 3 nanometers that have a relatively high density of low-energy quasi-particle states. Their spatial and spectroscopic characteristics are consistent with theories of strong quasi-particle scattering from atomic-scale impurities in a d-wave superconductor. These characteristics include breaking of local particle-hole symmetry, a diameter near twice the superconducting coherence length, and an inverse square dependence of their local density-of-states on distance from the scattering center. In addition to the validation of d-wave quasi-particle scattering theories, these observations identify a source for the anomalously high levels of low-energy quasi-particles in Bi2Sr2CaCu2O8+delta at low temperatures.