Dual mutations in the whitefly nicotinic acetylcholine receptor ß1 subunit confer target-site resistance to multiple neonicotinoid insecticides.

Neonicotinoid insecticides, which target insect nicotinic acetylcholine receptors (nAChRs), have been widely and intensively used to control the whitefly, Bemisia tabaci, a highly damaging, globally distributed, crop pest. This has inevitably led to the emergence of populations with resistance to neonicotinoids. However, to date, there have been no reports of target-site resistance involving mutation of B. tabaci nAChR genes. Here we characterize the nAChR subunit gene family of B. tabaci and identify dual mutations (A58T&R79E) in one of these genes (BTß1) that confer resistance to multiple neonicotinoids. Transgenic D. melanogaster, where the native nAChR Dß1 was replaced with BTß1A58T&R79E, were significantly more resistant to neonicotinoids than flies where Dß1 were replaced with the wildtype BTß1 sequence, demonstrating the causal role of the mutations in resistance. The two mutations identified in this study replace two amino acids that are highly conserved in >200 insect species. Three-dimensional modelling suggests a molecular mechanism for this resistance, whereby A58T forms a hydrogen bond with the R79E side chain, which positions its negatively-charged carboxylate group to electrostatically repulse a neonicotinoid at the orthosteric site. Together these findings describe the first case of target-site resistance to neonicotinoids in B. tabaci and provide insight into the molecular determinants of neonicotinoid binding and selectivity.

Long-Term Aging Study on the Solid State Interfacial Reactions of In on Cu Substrate.

Indium is considered a candidate low-temperature solder because of its low melting temperature and excellent mechanical properties. However, the solid-state microstructure evolution of In with different substrates has rarely been studied due to the softness of In. To overcome this difficulty, cryogenic broad Ar+ beam ion polishing was used to produce an artifact-free Cu/In interface for observation. In this study, we accomplished phase identification and microstructure investigation at the Cu/In interface after long-term thermal aging. CuIn2 was observed to grow at the Cu/In interface and proved to be a stable phase in the Cu-In binary system. The peritectoid temperature of the Cu11In9 + In → CuIn2 reaction was confirmed to be between 100 and 120 °C. In addition, the growth rate of CuIn2 was discovered to be dominated by the curvature of the reactant Cu11In9/In phase and the temperature difference with the peritectoid temperature. Finally, a comprehensive microstructural evolution mechanism of the Cu/In solid-state interfacial reaction was proposed.

An Update on Recent Advances of Photodynamic Therapy for Primary Cutaneous Lymphomas.

Primary cutaneous lymphomas are rare non-Hodgkin lymphomas consisting of heterogeneous disease entities. Photodynamic therapy (PDT) utilizing photosensitizers irradiated with a specific wavelength of light in the presence of oxygen exerts promising anti-tumor effects on non-melanoma skin cancer, yet its application in primary cutaneous lymphomas remains less recognized. Despite many in vitro data showing PDT could effectively kill lymphoma cells, clinical evidence of PDT against primary cutaneous lymphomas is limited. Recently, a phase 3 "FLASH" randomized clinical trial demonstrated the efficacy of topical hypericin PDT for early-stage cutaneous T-cell lymphoma. An update on recent advances of photodynamic therapy in primary cutaneous lymphomas is provided.

Artifact-Free Microstructures in the Interfacial Reaction between Eutectic In-48Sn and Cu Using Ion Milling.

Eutectic In-48Sn was considered a promising candidate for low-temperature solder due to its low melting point and excellent mechanical properties. Both Cu2(In,Sn) and Cu(In,Sn)2 formation were observed at the In-48Sn/Cu interface after 160 °C soldering. However, traditional mechanical polishing produces many defects at the In-48Sn/Cu interface, which may affect the accuracy of interfacial reaction investigations. In this study, cryogenic broad Ar+ beam ion milling was used to investigate the interfacial reaction between In-48Sn and Cu during soldering. The phase Cu6(Sn,In)5 was confirmed as the only intermetallic compound formed during 150 °C soldering, while Cu(In,Sn)2 formation was proven to be caused by room-temperature aging after soldering. Both the Cu6(Sn,In)5 and Cu(In,Sn)2 phases were confirmed by EPMA quantitative analysis and TEM selected area electron diffraction. The microstructure evolution and growth mechanism of Cu6(Sn,In)5 during soldering were proposed. In addition, the Young's modulus and hardness of Cu6(Sn,In)5 were determined to be 119.04 ± 3.94 GPa and 6.28 ± 0.13 GPa, respectively, suggesting that the doping of In in Cu6(Sn,In)5 has almost no effect on Young's modulus and hardness.

Current status on independent school health department in the centers for disease control and prevention across China / 中国学校卫生

Objective@#To understand the current status of main professional work in independent school health departments of Chinese centers for disease control and prevention, so as to provide reference and suggestions for the further development of school health work in China.@*Methods@#Electronic questionnaire was used to collect the basic work of school health, the monitoring work, the intervention action of common diseases and the development of health intervention among students in independent school health departments of centers for disease control and prevention in China.@*Results@#Among the 357 institutions that have set up independent school health departments, the implementation rates of school mental health work, safety emergency and risk avoidance health intervention were low, which were 11.8% and 11.5%, respectively. Relying on the project "national monitoring and intervention of common diseases and health influencing factors of students", the overall implementation of health monitoring in schools nationwide was successful, but the overall implementation rate of students nutritional status monitoring and "healthy parents action" were low, accounting for 44.5% and 24.4%, respectively. At the same time, there were still as many as 27.2% institutions that had not carried out the intervention action for common diseases of students which advocated in the monitoring program. The failure rate of county level institutions was higher than that of provincial level and prefecture level institutions, and the failure rate of the central and western institutions was much higher than that of the eastern institutions; the difference was statistically significant( χ 2=30.1, 41.6, P <0.05).@*Conclusion@#We should increase support including policy preference, fund guarantee, technical guidance and so on for the school health work of disease control institutions at the grass roots level and in economically underdeveloped areas, so as to ensure the healthy growth of children and adolescents in all respects.

Separation, characterization and anti-psoriasis effect of self-assembled nanoparticles from Shaoyao Gancao Decoction / 中国中药杂志

This study aims to separate and characterize self-assembled nanoparticles(SAN) from Shaoyao Gancao Decoction(SGD) and determine the content of active compounds. Further, we aimed to observe the therapeutic effect of SGD-SAN on imiquimod-induced psoriasis in mice. The separation of SGD was performed by dialysis, and the separation process was optimized by single factor experiment. The SGD-SAN isolated under the optimal process was characterized, and the content of gallic acid, albiflorin, paeoniflorin, liquiritin, isoliquiritin apioside, isoliquiritin, and glycyrrhizic acid in each part of SGD was determined by HPLC. In the animal experiment, mice were assigned into a normal group, a model group, a methotrexate group(0.001 g·kg~(-1)), and SGD, SGD sediment, SGD dialysate, and SGD-SAN groups of different doses(1, 2, and 4 g·kg~(-1)) respectively. The psoriasis grade of mice was evaluated based on the pathological changes of skin lesions, the content of inflammatory cytokines, organ index and other indicators. The results showed that SAN obtained by centrifugation at 13 000 r·min~(-1) for 30 min was stable after dialysis for 4 times, which were uniform spherical nanoparticles with the particle size of(164.43±1.34) nm, the polydispersity index of(0.28±0.05), and the Zeta potential of(-12.35±0.80) mV. The active compound content accounted for more than 70% of SGD. Compared with the model group, SAN and SGD decreased the skin lesion score, spleen index, and inflammatory cytokine levels(P<0.05 or P<0.01) and alleviated the skin thickening and infiltration of inflammatory cells. However, the sediment group and the dialysate group had no obvious effect. SGD showed a good therapeutic effect on imiquimod-induced psoriasis in mice, and SAN demonstrated the effect equivalent to SGD in a dose-dependent manner. Therefore, we conclude that the SAN formed during decocting is the main active form of SGD, which can lower the levels of inflammatory cytokines, promote the normal differentiation of keratinocytes, and reduce the infiltration of inflammatory cells in the treatment of psoriasis lesions in mice.

Effect of Morus alba extract sanggenon C on growth and proliferation of glioblastoma cells / 中国中药杂志

Glioblastoma is the most common primary cranial malignancy, and chemotherapy remains an important tool for its treatment. Sanggenon C(San C), a class of natural flavonoids extracted from Morus plants, is a potential antitumor herbal monomer. In this study, the effect of San C on the growth and proliferation of glioblastoma cells was examined by methyl thiazolyl tetrazolium(MTT) assay and 5-bromodeoxyuridinc(BrdU) labeling assay. The effect of San C on the tumor cell cycle was examined by flow cytometry, and the effect of San C on clone formation and self-renewal ability of tumor cells was examined by soft agar assay. Western blot and bioinformatics analysis were used to investigate the mechanism of the antitumor activity of San C. In the presence of San C, the MTT assay showed that San C significantly inhibited the growth and proliferation of tumor cells in a dose and time-dependent manner. BrdU labeling assay showed that San C significantly attenuated the DNA replication activity in the nucleus of tumor cells. Flow cytometry confirmed that San C blocked the cell cycle of tumor cells in G_0/G_1 phase. The soft agar clone formation assay revealed that San C significantly attenuated the clone formation and self-renewal ability of tumor cells. The gene set enrichment analysis(GSEA) implied that San C inhibited the tumor cell division cycle by affecting the myelocytomatosis viral oncogene(MYC) signaling pathway. Western blot assay revealed that San C inhibited the expression of cyclin through the regulation of the MYC signaling pathway by lysine demethylase 4B(KDM4B), which ultimately inhibited the growth and proliferation of glioblastoma cells and self-renewal. In conclusion, San C exhibits the potential antitumor activity by targeting the KDM4B-MYC axis to inhibit glioblastoma cell growth, proliferation, and self-renewal.

Application characteristics of Qugu (CV 2) in ancient and modern literature / 中国针灸

To summarize and analyze the clinical application characteristics of Qugu (CV 2) in ancient and modern literature based on data mining technology. The Chinese Medical Code (the 5th edition) was taken as the retrieval source of ancient literature, while the CNKI, Wanfang, and VIP databases were taken as the retrieval source of modern literature. The indications of Qugu (CV 2) used alone or with compatible acupoints, compatible acupoints, acupuncture-moxibustion manipulation, etc., were systematically sorted out. As a result, a total of 140 articles of ancient literature were included. The common indications of Qugu (CV 2) used alone were urinary retention, profuse vaginal discharge and hernia. The common indications of Qugu (CV 2) used with compatible acupoints were profuse vaginal discharge, stranguria and hernia. Sixty-four acupoints were concurrently used with Qugu (CV 2), Qugu (CV 2) was mainly compatible with acupoints of conception vessel, bladder meridian and liver meridian, and the high-frequency acupoints included Zhongji (CV 3), Guanyuan (CV 4) and Sanyinjiao (SP 6); five-shu points were the most used special acupoints, and moxibustion therapy was often used. A total of 73 modern articles were included. The common indications of Qugu (CV 2) used alone were urinary retention, erectile dysfunction and chronic prostatitis; the common indications of Qugu (CV 2) used with compatible scupoints were urinary retention, erectile dysfunction and prostatic hyperplasia. Thirty-six acupoints were concurrently used with Qugu (CV 2), Qugu (CV 2) was mainly compatible with acupoints of conception vessel, kidney meridian and spleen meridian, and the high-frequency acupoints included Zhongji (CV 3), Guanyuan (CV 4) and Zusanli (ST 36); front-mu points were the most used special acupoints, and acupuncture therapy was often used. Qugu (CV 2) treats a wide range of diseases in ancient times, the distant treatment effectiveness of acupoints is emphasized; and it mainly treats local diseases in modern times, the nearby treatment effectiveness of acupoints is emphasized.

The value of immune inflammatory index in predicting the therapeutic efficacy of neoadju-vant chemoradiotherapy for esophageal squamous cell carcinoma / 中华消化外科杂志

Objective:To investigate the value of immune inflammatory index in predic-ting the therapeutic efficacy of neoadjuvant chemoradiotherapy for esophageal squamous cell carci-noma (ESCC).Methods:The retrospective case-control study was conducted. The clinicopatholo-gical data of 163 patients with ESCC who were admitted to Zhongshan Hospital of Fudan University from December 2015 to December 2020 were collected. There were 135 males and 28 females, aged (62±8)years. All 163 patients underwent neoadjuvant chemoradiotherapy and radical resection for ESCC. Observation indicators: (1) relationship between immune inflammatory index and clinical characteristic in patients; (2) relationship between immune inflammatory index and efficacy of neoadjuvant chemoradiotherapy in patients; (3) influencing factor analysis for pathologic complete response and good response of tumor regression grade after neoadjuvant chemoradiotherapy; (4) efficiency of immune inflammatory index in predicting efficacy of neoadjuvant chemoradiotherapy. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers, and comparison between groups was conducted using chi-square test. Comparison of ordinal data was conducted using the rank sum test. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value. Univariate and multi-variate analyses were conducted using the Logistic regression model. The area under the curve (AUC) of ROC curve was used to evaluate the efficiency of predictive model. Results:(1) Relationship between immune inflammatory index and clinical characteristic in patients. ① Optimal cut-off value of systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR), platelet-lympho-cyte ratio (PLR). Results of ROC curve analysis showed that the AUC of SII, NLR, PLR in predicting efficacy of neoadjuvant chemoradiotherapy for patients with ESCC was 0.70(95% confidence interval as 0.61?0.77), 0.78(95% confidence interval as 0.69?0.84), 0.79(95% confidence interval as 0.70?0.85), respectively, with the maximum value of Youden index and the optimal cut-off value as 0.25, 0.32, 0.52 and 446×10 9/L, 2.09, 138. ② Relationship between SII, NLR, PLR and clinical charac-teristic in patients. According to the optimal cut-off value of SII, NLR, PLR, all 163 patients were divided into cases with SII <446×10 9/L as 99, cases with SII ≥446×10 9/L as 64, cases with NLR <2.09 as 107, cases with NLR ≥2.09 as 56, cases with PLR<138 as 88, cases with PLR ≥138 as 75, respectively. There was a significant difference in clinical N staging of tumor in patients with SII <446×10 9/L and SII ≥446×10 9/L ( P<0.05). There were significant differences in clinical N staging and clinical TNM staging of tumor in patients with NLR<2.09 and NLR≥2.09 ( P<0.05). (2) Relationship between immune inflammatory index and efficacy of neoadjuvant chemoradiotherapy in patients. Of 163 patients undergoing neoadjuvant chemoradiotherapy, there were 54 cases with pathologic complete response and 109 cases without pathologic complete response, 94 cases with good response of tumor regression grade and 69 cases with poor response of tumor regression grade. Of the 54 patients with pathologic complete response, cases with SII <446×10 9/L and SII ≥446×10 9/L, cases with NLR <2.09 and NLR ≥2.09, cases with PLR <138 and PLR ≥138 before neoadjuvant chemoradiotherapy were 42 and 12, 47 and 7, 48 and 6, respectively. The above indicators were 57 and 52, 60 and 49, 40 and 69 in the 109 cases without pathologic complete response. There were significant differences in the above indicators between patients with pathologic complete response and without pathologic complete response ( χ2=9.83, 16.39, 39.60, P<0.05). Of the 94 cases with good response of tumor regression grade, cases with SII <446×10 9/L and SII ≥446×10 9/L, cases with NLR <2.09 and NLR ≥2.09, cases with PLR <138 and PLR ≥138 before neoadjuvant chemoradiotherapy were 59 and 35, 78 and 16, 56 and 38, respectively. The above indicators were 40 and 29, 29 and 40, 32 and 37 in the 69 cases with poor response of tumor regression grade. There was no significant difference in the SII and PLR ( χ2=0.38, 2.79, P>0.05) and there was a significant difference in the NLR ( χ2=29.59, P<0.05) between patients with good response of tumor regression grade and poor response of tumor regre-ssion grade. (3) Influencing factor analysis for pathologic complete response and good response of tumor regression grade after neoadjuvant chemoradiotherapy. Results of multivariate analysis showed that PLR <138 before neoadjuvant chemoradiotherapy was an independent protective factor for pathologic complete response in ESCC patients undergoing neoadjuvant chemoradiotherapy ( odds ratio=1.98, 95% confidence interval as 1.56?2.51, P<0.05) and NLR <2.09 before neoadjuvant chemo-radiotherapy was an independent protective factor for good response of tumor regression grade ( odds ratio=2.50, 95% confidence interval as 1.40?4.46, P<0.05). (4) Efficiency of immune inflam-matory index in predicting efficacy of neoadjuvant chemoradio-therapy. The AUC of PLR <138 before neoadjuvant chemoradiotherapy in predicting pathologic complete response of ESCC patients undergoing neoadjuvant chemoradiotherapy was 0.79(95% confidence interval as 0.64?0.87, P<0.05), with the sensitivity, specificity and Youden index as 0.89, 0.63 and 0.52, respectively. The AUC of NLR <2.09 before neoadjuvant chemoradiotherapy in predic-ting good response of tumor regression grade of ESCC patients undergoing neoadjuvant chemoradio-therapy was 0.76 (95% confidence interval as 0.64?0.81, P<0.05), with the sensitivity, specificity and Youden index as 0.83, 0.58 and 0.41, respectively. Conclusion:The PLR<138 and NLR <2.09 before neoadjuvant chemoradiotherapy are independent protective factors for the pathologic complete response and good response of tumor regression grade, respectively, of ESCC patients undergoing neoadjuvant chemoradiotherapy, and both of them can predict the curative effect of neoadjuvant chemoradiotherapy well.

Exploration of the diagnosis and treatment for benign prostatic hyperplasia with acupuncture based on jingjin theory / 中国针灸

Benign prostatic hyperplasia is caused by kidney deficiency and impaired qi transformation of the urinary bladder and is manifested by the stagnation of essence chamber. Based on jingjin (muscle region of meridian, sinew/fascia) theory and taking the visceral membrane as the principal, acupuncture is delivered at sinew/fascia to promote qi circulation, resolve stasis and open the orifice. Guided by CT, the needle is inserted at Zhongji (CV 3), the front-mu point of the urinary bladder, and then goes to the prostatic capsule, meaning "the disease of zang organ is treated by needling the front-mu point". In treatment of benign prostatic hyperplasia, this acupuncture therapy stimulates the different layers of fascia, by which, the defensive qi on the exterior is regulated and "essence orifice" in the interior is adjusted so that the urination can be promoted.

Investigational Treatments for Epidermolysis Bullosa.

Epidermolysis bullosa (EB) is a heterogeneous group of rare inherited blistering skin disorders characterized by skin fragility following minor trauma, usually present since birth. EB can be categorized into four classical subtypes, EB simplex, junctional EB, dystrophic EB and Kindler EB, distinguished on clinical features, plane of blister formation in the skin, and molecular pathology. Treatment for EB is mostly supportive, focusing on wound care and patient symptoms such as itch or pain. However, therapeutic advances have also been made in targeting the primary genetic abnormalities as well as the secondary inflammatory footprint of EB. Pre-clinical or clinical testing of gene therapies (gene replacement, gene editing, RNA-based therapy, natural gene therapy), cell-based therapies (fibroblasts, bone marrow transplantation, mesenchymal stromal cells, induced pluripotential stem cells), recombinant protein therapies, and small molecule and drug repurposing approaches, have generated new hope for better patient care. In this article, we review advances in translational research that are impacting on the quality of life for people living with different forms of EB and which offer hope for improved clinical management.

An integrative metabolomics and network pharmacology method for exploring bioactive components and preliminary pharmacodynamics in medicinal parts of Harrisonia perforata / 中国中药杂志

In this paper,metabolomics and network pharmacology were used to investigate the bioactive components of Harrisonia perforata and their possible mechanisms of action. Metabolites in the flowers,fruits,branches,leaves and stalks of H. perforata were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Meanwhile,multiple statistical analysis methods including principal component analysis( PCA) and orthogonal partial least squares discriminant analysis( OPLS-DA)were applied to screen and identify differential compounds. With metabolomics method,9 differential compounds were preliminarily identified from leaves and other non-traditional medicinal parts. Subsequently,these compounds were explored by using network pharmacology. With gastrointestinal absorption and drug-likeness as limiting conditions,they were imported into the Swiss ADME,from which 7 compounds with potential medicinal activity were obtained. Then,their targets were predicted by PharmMapper,with Human Protein Targets Only and Normalized Fit Score>0. 9 set as limiting conditions,and 60 standardized potential targets were identified with Uniprot. KEGG( Kyoto encyclopedia of genes and genomes) pathway data was obtained using metascape and the " potential active ingredients-target-pathway" network was constructed with Cytoscape 3. 7. 2. The enrichment analysis of KEGG demonstrated that the 60 targets were enriched in 78 signaling pathways( min overlap: 3,P value cutoff: 0. 01,min enrichment: 1. 5),many of which are related to anti-bacteria,anti-inflammation and anti-virus,such as IL-17 signaling pathway,RIG-I-like receptor signaling pathway and NOD-like receptor signaling pathway. Finally,depending on the clinical activity of H. perforata,the relevant signaling pathways were analyzed through experimental data and literature. Dehydroconiferyl alcohol was reported to have the anti-inflammatory effect and perforamone D to possess the antimycobacterial activity. The KEGG pathway enrichment analysis showed that dehydroconiferyl alcohol could act on the Alzheimer's disease( AD) signaling pathway by targeting CDK5 R1 and BACE1. ACh E inhibitor is the most promising drug to treat AD,while dehydroconiferyl alcohol has been proved to inhibit ACh E according to literature. The experimental results revealed that the extract of leaves of H. perforata can effectively inhibit the growth of Staphylococcus aureus. These are consistent with the enrichment analysis results of KEGG. This study explored the bioactive components and pharmacodynamics of the leaves of the H. perforata,laying a theoretical foundation for its in-depth development and rational application.

Human CD31 on Swine Endothelial Cells Induces SHP-1 Phosphorylation in Macrophages.

BACKGROUND: Innate immunity by natural killer (NK) cells, macrophages, and neutrophils cause severe rejections in xenotransplantation. Therefore, the development of strategies for suppressing macrophages has considerable potential in practical applications of xenotransplantation. Recently, we found that human CD31 on swine endothelial cells (SECs) suppresses neutrophil-mediated xenogeneic rejection through homophilic binding. Since a significant amount of CD31 is expressed not only on neutrophils but also on macrophages, we studied the function of human CD31 in macrophage-mediated cytotoxicity. METHODS: SECs and hCD31-transfected SECs (SEC/hCD31) were co-cultured with macrophages and cytotoxicity by macrophages was evaluated with water-soluble tetrazolium salt, or WST-8, assay. To confirm whether or not inhibitory signals are induced by hCD31 homophilic binding, the phosphorylation of the enzyme SHP-1 was investigated with Western blotting. RESULTS: No suppression of cytotoxicity was induced in macrophages that had been co-cultured with SEC/CD31. However, phosphorylation of SHP-1 was induced in macrophages that had been co-cultured with SEC/hCD31. CONCLUSIONS: Human CD31 on SEC may induce not only inhibitory signals but also activation signals via the binding to other receptors for hCD31.

Role-play in Endodontic Teaching: a Case Study.

Objective: To investigate the role of the application of role-play in endodontic study in improving the communication skills of Chinese dental undergraduates prior to their direct interactions with patients at the Fourth Military Medical University's School of Stomatology, China. Methods: Students were recruited from the 5-year bachelor's programme (n = 36) and randomly divided into six groups, and from the 8-year DDS programme (n = 10) and randomly divided into two groups to participate in the role-play training. Cases selected randomly from the case pool were distributed to the groups. The teacher gave an outline of the roles in the simulation. Each member of each group randomly selected their own role for the role-play. Four types of surveys were distributed to students and faculty members at different points after the role-plays had taken place, to evaluate their attitude towards the use of role-plays in endodontic study. Frequency analysis and a one sample t test were used to describe and analyse students' acceptance of role-play as a teaching technique. The level of statistical significance was set at P < 0.05. Results: Students' performance and satisfaction as well as the supporting faculty responses were very favourable towards role-playing. In total, 93.5% of students responded favourably to the role-play, answering 'strongly agree' or 'agree' to the positive statements about their role-play performance. A total of 95.1% of students stated that they had benefited psychologically and technically from the role-play ('strongly agree' or 'agree') after their 1-year rotating internship. Conclusion: The application of role-play in endodontic study is an effective way of educating Chinese dental undergraduates and can be beneficial for their transition from students to dentists.

A Strategy for Suppressing Macrophage-mediated Rejection in Xenotransplantation.

Although xenografts are one of the most attractive strategies for overcoming the shortage of organ donors, cellular rejection by macrophages is a substantial impediment to this procedure. It is well known that macrophages mediate robust immune responses in xenografts. Macrophages also express various inhibitory receptors that regulate their immunological function. Recent studies have shown that the overexpression of inhibitory ligands on porcine target cells results in the phosphorylation of tyrosine residues on intracellular immunoreceptor tyrosine-based inhibitory motifs on macrophages, leading to the suppression of xenogenic rejection by macrophages. It has also been reported that myeloid-derived suppressor cells, a heterogeneous population of immature myeloid cells, suppress not only NK and cytotoxic T lymphocyte cytotoxicity but also macrophage-mediated cytotoxicity. This review is focused on the recent findings regarding strategies for inhibiting xenogenic rejection by macrophages.

Bronchial epithelium repair by Esculentin-1a-derived antimicrobial peptides: involvement of metalloproteinase-9 and interleukin-8, and evaluation of peptides' immunogenicity.

The airway epithelium is seriously damaged upon pulmonary Pseudomonas aeruginosa infection, especially in cystic fibrosis (CF) sufferers. Therefore, the discovery of novel anti-infective agents accelerating healing of infected injured tissues is crucial. The antipseudomonal peptides esculentin-1a(1-21)NH2 and its diastereomer Esc(1-21)-1c (Esc peptides) hold promise in this respect. In fact, they stimulate airway epithelial wound repair, but no mechanistic insights are available. Here we demonstrated that this process occurs through promotion of cell migration by an indirect activation of epidermal growth factor receptor mediated by metalloproteinases. Furthermore, we showed an increased expression of metalloproteinase 9, at both gene and protein levels, in peptide-treated bronchial epithelial cells with a functional or mutated form of CF transmembrane conductance regulator. In addition, the two peptides counteracted the inhibitory effect of Pseudomonas lipopolysaccharide (mimicking an infection condition) on the wound healing activity of the airway epithelium, and they enhanced the production of interleukin-8 from both types of cells. Finally, no immunogenicity was discovered for Esc peptides, suggesting their potential safety for clinical usage. Besides representing a step forward in understanding the molecular mechanism underlying the peptide-induced wound healing activity, these studies have contributed to highlight Esc peptides as valuable therapeutics with multiple functions.

Pre- and post-treatment changes of gingvitis-associated peptidomic profiles in the saliva and gingival crevicular fluid by mass spectrometry / 中华口腔医学杂志

Objective@#To explore peptidomic changes of peptides in saliva and gingival crevicular fluid (GCF) before and after treatment of gingivitis.@*Methods@#From January 2017 to September 2017, seventeen participants at the age of 24-62 (6 males and 11 females) at Department of Preventive Dentistry, Peking University School and Hospital of Stomatology with gingivitis were recruited in the present study. Their clinical parameters were measured and recorded. Saliva and GCF samples were collected from each of the participants at the baseline and 7 days after ultrasonic supragingival scaling, respectively. Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) was employed to detect the changes of peptidomic profiles, while ano-liquid chromatography-electrospray ionization-tandem mass spectrometry (nano-LC/ESI-MS/MS) was performed to identify the possible proteins from which the peptides might derive.@*Results@#Initially, four peptide peaks [mass-to-charge ratio (m/z) values: 1 030.6, 1 043.4, 1 053.4 and 1 064.6] were screened out exhibiting a decreasing trend after treatment (P<0.05). Besides, five peptide peaks from gingival crevicular fluid (P<0.05) exhibited differential expression, among which 1 055.5 and 1 168.3 demonstrating a decrease after treatment, while 3 363.7, 3 480.9 and 3 489.5 increased overtime. Certain positive correlations were detected between some peptides and clinical parameters. Principle component analysis using the above mentioned peptide peaks showed a distinct distribution before and after treatment and peptides from GCF showed a slightly better capacity to discriminate patients before and after treatment. The peptides with m/z values of 1 055.5 in GCF and 1 064.6 in saliva were identified to be segments of serum albumin and complement C3, respectively.@*Conclusions@#Several differentially expressed peptides were detected in saliva and GCF by MALDI-TOF MS, exhibiting the potentiality to act as biomarkers in gingivitis patients.

Application value of modified serf-traction Overlap method in intrathoracic esophagogastrostomy of Ivor Lewis surgery / 中华消化外科杂志

Objective To explore the application value of modified self-traction Overlap method in intrathoracic esophagogastrostomy of Ivor Lewis surgery.Methods The retrospective and descriptive study was conducted.The clinical data of 12 patients with lower esophageal carcinoma who underwent Ivor Lewis surgery in the Zhongshan Hospital of Fudan University from January to May 2018 were collected.There were 9 males and 3 females,aged from 50 to 73 years,with a median age of 61 years.Modified self-traction Overlap method was used for intrathoracic esophagogastrostomy during the surgery.The esophagus was pulled down with the ligature as traction and rotated clockwise by 45 degrees to perform side-to-side esophagogastric anastomosis.The common opening was closed by a laparoscopic linear cutting suturing device to form an esophagogastric Overlap triangle anastomosis,and finally the esophagus was disconnected.Observation indicators:(1) intraoperative and postoperative situations;(2) follow-up situations.Follow-up using outpatient examination and telephone interview was performed to detect survival situation and tumor recurrence and metastasis up to January 2019.Measurement data were described as M (range).Results (1) Intraoperative and postoperative situations:all the 12 patients underwent successful Ivor Lewis surgery,without conversion to open surgery.The operation time,time of tubular gastroesophageal anastomosis,volume of intraoperative blood loss,time to initial anal exsufflation and time for initial fluid diet intake were 145 minutes (range,125-189 minutes),20 minutes (range,16-35 minutes),98 mL (range,78-135 mL),4 days (range,3-5 days),6 days (range,5-7 days),respectively.All the patients had no complication.Patients underwent upper gastrointestinal iodine hydrography at 5 days after surgery,confirming no anastomotic leakage or stenosis.Patients recovered well and were discharged postoperatively.The duration of postoperative hospital stay was 8 days (range,7-11 days).(2) Follow-up situations:12 patients were followed up for 8.0-12.0 months,with a median time of 10.6 months.Patients survived well,with no tumor recurrence or metastasis.Condusion Modified self-traction Overlap method in thoracic esophagogastrostomy of Ivor Lewis surgery is safe and feasible for lower esophageal carcinoma,with easy operating