Efficacy of nature killer cell combination chemotherapy for post-radical gastric cancer metastases: Case report.

Nature killer cell therapy has shown strong efficacy in the field of oncology in recent years and has been applied to patients with metastases with the aim of improving the prognosis of advanced gastric cancer. A 59-year-old male with gastric adenocarcinoma with pancreatic metastasis (T4N0M1) who underwent radical surgery for gastric cancer with tumor metastasis was treated with oxaliplatin and tegafur combined with cellular reinfusion in stages. Computed tomograpy scan and serum tumor markers were monitored continuously after the treatment course. After five courses of combined treatment, the patient was in disease control with no significant side effects. At the last follow-up, the alpha fetoprotein had returned to its normal value with a poor display of low-density shadows in the body of the pancreas. Pancreatic cancer is insidious in origin and has a high mortality rate. The report provides clinical evidence for cell therapy of pancreatic metastatic cancer with improved quality of life.

Evaluation of Dry Eye Severity and Ocular Surface Inflammation in Patients with Autoimmune Rheumatic Diseases.

PURPOSE: To evaluate dry eye severity and ocular surface inflammation in autoimmune rheumatic diseases (ARDs). METHODS: Seventy-nine patients with ARDs were enrolled, including 26 patients with rheumatoid arthritis (RA), 33 patients with systemic lupus erythematosus (SLE), and 20 patients with primary Sjögren's syndrome (pSS). All patients underwent ocular surface evaluations, including ocular surface symptoms, signs, conjunctival impression cytology, and tear multicytokine detection. Systemic conditions, including disease duration, disease activity, and serological parameters, were also noted. RESULTS: SLE patients had the shortest disease duration, and nearly half of them had low disease activity, while RA patients and pSS patients had a relatively long disease duration, and approximately 90% of them had moderate or high disease activity. The incidence of dry eye and the levels of the proinflammatory tear cytokines in SLE were significantly lower than those in RA and pSS. However, ocular surface squamous metaplasia was more severe in SLE and pSS than in RA. Dry eye severity in all ARD patients was shown to be independent of disease activity, while Nelson's grades were positively correlated with disease duration in RA patients. Disease-related serological parameters were associated with tear proinflammatory cytokines in all ARD patients. CONCLUSIONS: Variable degrees of dry eye and immune-mediated ocular surface inflammation persist in different ARD patients. In addition to a well-known association between dry eye and pSS, dry eye is also commonly observed in SLE and RA patients. Therefore, there is a definite need for regular ophthalmologic evaluations and topical medications in all patients with ARDs.

Evaluation of Dry Eye Severity and Ocular Surface Inflammation in Patients with Pemphigus and Pemphigoid.

PURPOSE: To evaluate ocular surface involvement, tear cytokine levels, and histopathological changes in pemphigus and pemphigoid patients. METHODS: A total of 22 patients (15 pemphigus and 7 pemphigoids) and 21 non-diseased controls were enrolled in our study. All participants underwent ocular surface evaluation, which included ocular surface disease index test, slit lamp observation, dry eye-related examination, tear multicytokine analysis, and conjunctival impression cytology. RESULTS: Pemphigus and pemphigoid patients presented much more severe conjunctivochalasis, corneal epithelial defects, corneal opacity, symblepharon   and dry eye. Severe ocular surface squamous metaplasia and a significant increase of tear macrophage inflammatory protein-1beta, tumor necrosis factor-alpha, interleukin (IL)-1ß, IL -6, and IL-8 occurred in pemphigus and pemphigoid patients. CONCLUSIONS: Our results revealed that ocular surface inflammation and dry eye persist in most pemphigus and pemphigoid patients, and do not occur in parallel with the systemic course. Regular ophthalmological examinations and local anti-inflammatory should be provided for pemphigus and pemphigoid patients.

Human mesenchymal stem cells derived from adipose tissue showed a more robust effect than those from the umbilical cord in promoting corneal graft survival by suppressing lymphangiogenesis.

BACKGROUND: Mesenchymal stem cells (MSCs) have shown promising potential in allograft survival. However, few reports have focused on comparing the immunosuppressive capacity of MSCs from different sources and administered via different routes in inhibiting transplant rejection. Moreover, virtually nothing is known about the role of MSCs in the regulation of graft neovascularization and lymphangiogenesis. In this study, we compared the efficacy of human adipose MSCs (hAD-MSCs) and human umbilical cord MSCs (hUC-MSCs) in vitro and in corneal transplantation models to explore the underlying molecular mechanisms and provide a powerful strategy for future clinical applications. METHODS: hAD-MSCs and hUC-MSCs were generated, and their self-renewal and multi-differentiation abilities were evaluated. The inhibitory effect of human MSCs (hMSCs) was examined by T-cell proliferation assays with or without transwell in vitro. Two MSCs from different sources were separately adoptively transferred in mice corneal transplantation (5 × 105 or 1 × 106/mouse) via topical subconjunctival or intravenous (IV) routes. Allograft survival was evaluated every other day, and angiogenesis and lymphomagenesis were quantitatively analyzed by immunofluorescence staining. The RNA expression profiles of hMSCs were revealed by RNA sequencing (RNA-seq) and verified by quantitative real-time PCR (qRT‒PCR), western blotting or ELISA. The function of the differentially expressed gene FAS was verified by a T-cell apoptosis assay. RESULTS: hAD-MSCs induced stronger immunosuppression in vitro than hUC-MSCs. The inhibitory effect of hUC-MSCs but not hAD-MSCs was mediated by cell-cell contact-dependent mechanisms. Systemic administration of a lower dose of hAD-MSCs showed better performance in prolonging corneal allograft survival than hUC-MSCs, while subconjunctival administration of hMSCs was safer and further prolonged corneal allograft survival. Both types of hMSCs could inhibit corneal neovascularization, while hAD-MSCs showed greater superiority in suppressing graft lymphangiogenesis. RNA-seq analysis and confirmation experiments revealed the superior performance of hAD-MSCs in allografts based on the lower expression of vascular endothelial growth factor C (VEGF-C) and higher expression of FAS. CONCLUSIONS: The remarkable inhibitory effects on angiogenesis/lymphangiogenesis and immunological transplantation effects support the development of hAD-MSCs as a cell therapy against corneal transplant rejection. Topical administration of hMSCs was a safer and more effective route for application than systemic administration.

Ocular surface involvement and histopathologic changes in the acute stage of Stevens-Johnson syndrome and toxic epidermal necrolysis: a cross-sectional study.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and extremely serious drug-induced dermatological disorders. The ocular surface condition at the early stage has been little studied and should contribute to novel perspectives in early and effective topical therapy of these diseases. The objectives of the study were to evaluate the acute phase of ocular surface involvement and histopathologic changes in patients with acute SJS/TEN. METHODS: Ten patients with acute phase of SJS/TEN onset and eleven age- and sex-matched healthy volunteers were recruited. Ocular surface symptoms and signs, conjunctival impression cytology, and tear multi-cytokine were assessed. RESULTS: Ocular surface objective signs were normal at the acute stage of SJS/TEN, while most patients have abnormal ocular surface subjective symptoms and meibomian gland secretion. Conjunctival impression cytology showed a significant decrease in goblet cell density and severe ocular surface squamous metaplasia in acute SJS/TEN patients. Tear multi-cytokine analysis showed all 21 pro- and anti-inflammatory cytokines all sharply elevated. Goblet cell density was significantly negatively correlated with tear C-X3-C motif chemokine ligand 1 (CX3CL1) and interleukin 13. CONCLUSIONS: Severe pathologic squamous metaplasia and inflammation onset in the ocular surface at the acute stage of the SJS/TEN, even if the ocular surface condition seemed basically normal with adequate systemic immunosuppressant and general supportive treatment. Early topical anti-inflammatory therapy should be carried out actively.

Characterization and the cholesterol-lowering effect of dietary fiber from fermented black rice (Oryza sativa L.).

Black rice was fermented with Neurospora crassa, after which the dietary fiber (DF) extracted from it was characterized and evaluated for its cholesterol-lowering effect in mice. The findings demonstrated that fermentation increased the level of soluble DF from 17.27% ± 0.12 to 29.69% ± 0.26 and increased the adsorption capacity of DF for water, oil, cholesterol, glucose and sodium cholate. The fermented DF had a more loose and porous structure than that extracted from unfermented rice. Additionally, feeding with DF from the fermented black rice significantly reduced body weight, lowered total cholesterol levels and improved the lipid profile in mice gavaged with a high dose (5 g per kg bw) or a low dose (2.5 g per kg·bw). ELISA showed that the hepatic expression of typical proteins and enzymes that are involved in cholesterol metabolism was regulated by the fermented rice DF, leading to reduced cholesterol production and increased cholesterol clearance. The fermented DF also modified the gut microbiota composition (e.g. Firmicutes reduced and Akkermansia increased), which promoted the production of short-chain fatty acids. In conclusion, fermentation can modify the structure and function of DF in black rice and the fermented dietary fiber has excellent cholesterol lowering effects possibly by cholesterol adsorption, cholesterol metabolism modulation, and intestinal microflora regulation.

Evaluation and correlation analysis of ocular surface disorders and quality of life in autoimmune rheumatic diseases: a cross-sectional study.

OBJECTIVE: This cross-sectional study aimed to reveal the association between ocular surface disorders and psychological, physiological situations among autoimmune rheumatic patients. METHODS: Ninety autoimmune rheumatic patients (180 eyes) hospitalized in the Department of Rheumatology, The Second Xiangya Hospital, Central South University and 30 controls (60 eyes) were enrolled in the study. All participants were assessed for ocular surface disorders including dry eye disease (DED) by the Ocular Surface Disease Index (OSDI) for symptoms evaluation, and slim lamp examinations for tear break-up time (TBUT), meibomian gland secretion, symblepharon and corneal clarity, Schirmer I test, corneal fluorescein staining (CFS), lid-parallel conjunctival folds (LIPCOF). Systematic conditions were evaluated using the Short Form 36-Health Survey (SF-36) for health-related quality of life, Hospital Anxiety and Depression Scale (HADS) for anxiety and depression, Health Assessment Questionnaire-Disability Index (HAQ-DI) for difficulties in activities of daily living, and Pittsburgh Sleep Quality Index (PSQI) for sleep quality. Pearson and spearman's analysis were conducted to examine the relationship between systematic conditions and ocular surface conditions. RESULTS: The analyses were controlled for age and sex. 52.22% of eyes (94 in 180) of autoimmune rheumatic patients and 21.67% of eyes (13 in 60) of controls were diagnosed with DED. The autoimmune rheumatic patients showed significant higher OSDI score, fewer basal tear secretion, more severe CFS and conjunctivochalasis than controls. There were no statistically significant differences in TBUT, meibomian gland secretion, symblepharon, and corneal clarity between the two groups. For systematic conditions, autoimmune rheumatic patients had significantly lower SF-36 scores, higher anxiety scores, and HAQ-DI scores than controls. No statistically significant differences were detected in depression scores and PSQI between the two groups. Among autoimmune rheumatic patients, OSDI scores were moderately correlated with quality of life, anxiety, depression and sleep quality. CONCLUSION: Factors including quality of life, anxiety, depression, and sleep quality are associated with ocular surface conditions, especially DED symptoms. Management of systemic conditions and psychotherapy should also be considered as part of the treatment among autoimmune rheumatic patients.

Delivery of Fc-fusion Protein by a Recombinant Newcastle Disease Virus Vector.

Fc-fusion proteins (FCPs), a new generation biological medicine, have revolutionized the practice of medicines that treat diseases. However, complex manufacturing techniques are required for FCP production, casting the affordability and accessibility issues in low- and middle-income economies (LMIEs). Virus-vectored system may serve as a simple and cost-effective platform for FCP delivery. As a proof-of-concept study, Newcastle disease virus (NDV), a widely-used vector for vaccine generation, was used as a vector to express and deliver a model FCP composed of the hemagglutinin (HA) and IgG Fc. A recombinant NDV expressing the HA-Fc fusion protein was generated using reverse genetics, which had comparable replication and virulence to the parental virus. High levels of expression of soluble HA-Fc were detected in cell culture and embryonated chicken eggs inoculated with the recombinant NDV. In addition, the recombinant NDV replicated in the lung of mouse, delivering the HA-Fc protein to this organ. The HA-Fc expressed by NDV specifically bound to murine FcγRI, which was dependent on the presence of the Fc tag. The recombinant NDV induced high vector-specific antibody response, whereas it failed to elicit H7N9-specific antibody immunity in mice. The absence of HA-specific antibodies may be attributed to deficient incorporation of the HA-Fc protein into NDV virion particles. Our results indicated that NDV may be potentially used as a vector for FCP expression and delivery. This strategy may help to enhance the affordability and equal accessibility of FCP biological medicines, especially in LIMEs.

Ocular surface disorders affect quality of life in patients with autoimmune blistering skin diseases: a cross-sectional study.

BACKGROUND: Autoimmune blistering skin diseases (AIBD) are a group of rare chronic autoimmune diseases which are associated with ocular surface diseases especially dry eye disease. This study is designed to investigate the relationship between ocular surface disorders and quality of life among patients with autoimmune blistering skin diseases. METHODS: Twenty-four AIBD patients (18 pemphigus and 7 pemphigoid) and twenty-five non-AIBD controls were included. Ocular surface disease index (OSDI), ocular surface evaluation, including slit-lamp examination, Schirmer I test, tear break-up time, corneal fluorescein staining, lid-parallel conjunctival folds, meibomian gland evaluation, presence of symblepharon and corneal opacity were assessed. Life quality was evaluated by multiple questionnaires, including Medical Outcomes Study 36-Item Short Form Questionnaire (SF-36), Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Ocular surface tests and quality of life were compared between AIBD patients and non-AIBD controls. In the AIBD patients, the associations between ocular surface parameters and quality of life were also evaluated. RESULTS: 92% of AIBD patients and 87.5% of age- and sex-matched non-AIBD controls were diagnosed with dry eye in this study. Compared with non-AIBD controls, AIBD patients reported lower SF-36 scores (P < 0.05) and severer OSDI, Schirmer I test, tear break-up time, corneal fluorescein staining, presence of symblepharon and corneal opacity measures (P < 0.05). OSDI, Schirmer I test were correlated with SF-36 composite scores or scores on the SF-36 subscales. CONCLUSIONS: AIBD patients experience reduced quality of life and more severe ocular surface disorders including dry eye, symblepharon and corneal opacity. Early treatments of dry eye and collaborations among multidisciplinary physicians are necessary in patients with AIBD.

A new parameterization of uptake coefficients for heterogeneous reactions on multi-component atmospheric aerosols.

Based on laboratory studies and field observations, a new parameterization of uptake coefficients for heterogeneous reactions on multi-component aerosols is developed in this work. The equivalent ratio (ER) of inorganic aerosol is used to establish the quantitative relationship between the heterogeneous uptake coefficients and the composition of aerosols. Incorporating the new ER-dependent scheme, the WRF-CUACE model has been applied to simulate sulfate mass concentrations during December 2017 in the Beijing-Tianjin-Hebei region and evaluate the role of aerosol chemical components played in the sulfate formation. Simulated temporal variations and magnitudes of sulfate show good agreement with the observations by using this new scheme. From clean to polluted cases, although both dominant cations and anions increase significantly, the equivalent ratio decreases gradually and is closer to unity, representing the variation of aerosol compositions, which inhibits the heterogeneous uptake of SO2, with the uptake coefficient decreasing from 1 × 10-4 to 5.3 × 10-5. Based on this phenomenon, a self-limitation process for heterogeneous reactions with the increasing secondary inorganic aerosol from clean to polluted cases is proposed.

The association between ambient temperature and mortality of the coronavirus disease 2019 (COVID-19) in Wuhan, China: a time-series analysis.

BACKGROUND: The COVID-19 has caused a sizeable global outbreak and has been declared as a public health emergency of international concern. Sufficient evidence shows that temperature has an essential link with respiratory infectious diseases. The objectives of this study were to describe the exposure-response relationship between ambient temperature, including extreme temperatures, and mortality of COVID-19. METHODS: The Poisson distributed lag non-linear model (DLNM) was constructed to evaluate the non-linear delayed effects of ambient temperature on death, by using the daily new death of COVID-19 and ambient temperature data from January 10 to March 31, 2020, in Wuhan, China. RESULTS: During the period mentioned above, the average daily number of COVID-19 deaths was approximately 45.2. Poisson distributed lag non-linear model showed that there was a non-linear relationship (U-shape) between the effect of ambient temperature and mortality. With confounding factors controlled, the daily cumulative relative death risk decreased by 12.3% (95% CI [3.4, 20.4%]) for every 1.0 °C increase in temperature. Moreover, the delayed effects of the low temperature are acute and short-term, with the most considerable risk occurring in 5-7 days of exposure. The delayed effects of the high temperature appeared quickly, then decrease rapidly, and increased sharply 15 days of exposure, mainly manifested as acute and long-term effects. Sensitivity analysis results demonstrated that the results were robust. CONCLUSIONS: The relationship between ambient temperature and COVID-19 mortality was non-linear. There was a negative correlation between the cumulative relative risk of death and temperature. Additionally, exposure to high and low temperatures had divergent impacts on mortality.

Myeloid-derived suppressor cells improve corneal graft survival through suppressing angiogenesis and lymphangiogenesis.

Myeloid-derived suppressor cells (MDSC) are one of the major negative regulators of immune responses during many pathological conditions such as cancer and transplantation. Emerging evidence indicates that MDSC also contribute to tumor progression through their pro-angiogenic activity in addition to immunosuppressive function. However, virtually nothing is known about the role of MDSC in the regulation of neovascularization after transplantation. Here we showed that antibody-mediated depletion of MDSC in mice led to robust growth of blood and lymphatic neovessels and rapid allograft rejection after corneal penetrating keratoplasty. In contrast, adoptive transfer of ex vivo generated MDSC from cytokine-treated bone marrow cells (evMDSC) suppressed neovascularization and prolonged corneal allograft survival in an inducible nitric oxide synthase (iNOS)-dependent manner. Mechanistically, compared to naïve MDSC control, evMDSC have increased expression of an anti-angiogenic factor thrombospondin 1 (Tsp-1) and decreased expression of two critical pro-angiogenic factors, vascular endothelial growth factor A (VEGF-A), and VEGF-C. These findings demonstrate MDSC as a critical anti-angiogenic regulator during transplantation. Our study also indicates that evMDSC are a valuable candidate agent for development of novel cell therapy to improve allograft survival after transplantation.

A comparative study of international and Chinese public health emergency management from the perspective of knowledge domains mapping.

BACKGROUND: At the end of 2019, the outbreak of coronavirus disease 2019 (COVID-19) severely damaged and endangered people's lives. The public health emergency management system in China has played an essential role in handling the response to the outbreak, which has been appreciated by the World Health Organization and some countries. Hence, it is necessary to conduct an overall analysis of the development of the health emergency management system in China. This can provide a reference for scholars to aid in understanding the current situation and to reveal new research topics. METHODS: We collected 2247 international articles from the Web of Science database and 959 Chinese articles from the China National Knowledge Infrastructure database. Bibliometric and mapping knowledge domain analysis methods were used in this study for temporal distribution analysis, cooperation network analysis, and co-word network analysis. RESULTS: The first international article in this field was published in 1991, while the first Chinese article was published in 2005. The research institutions producing these studies mainly existed in universities and health organizations. Developed countries and European countries published the most articles overall, while eastern China published the most articles within China. There were 52 burst words for international articles published from 1999-2018 and 18 burst words for Chinese articles published from 2003-2018. International top-ranked articles according to the number of citations appeared in 2005, 2007, 2009, 2014, 2015, and 2016, while the corresponding Chinese articles appeared in 2003, 2004, 2009, and 2011. CONCLUSIONS: There are differences in the regional and economic distribution of international and Chinese cooperation networks. International research is often related to timely issues mainly by focusing on emergency preparedness and monitoring of public health events, while China has focused on public health emergencies and their disposition. International research began on terrorism and bioterrorism, followed by disaster planning and emergency preparedness, epidemics, and infectious diseases. China considered severe acute respiratory syndrome as the starting research background and the legal system construction as the research starting point, which was followed by the mechanism, structure, system, and training abroad for public health emergency management.

High-level expression of LMW-GS and α-gliadin genes promoted by the expressed tag sequence of 5' end in Escherichia coli.

Wheat storage protein genes, especially low molecular weight glutenin subunit (LMW-GS) and gliadin genes are difficult to be expressed in Escherichiacoli, mainly due to the presence of highly repetitive sequences. In order to establish a high efficiency expression system for these genes, five different expression plasmids combining with 9 genes, viz. 6 LMW-GS and 3 α-gliadin genes isolated from common wheat and related species, were studied for heterologous expression in E. coli. In this study, when an expressed tag sequence encoding signal peptide, His-S or GST-tag was fused to the 5' end of LMW-GS or gliadin gene as the leading sequence, all recombination genes could be stably expressed at a high level. On the contrast, as expected, the inserted genes encoding mature protein failed without an expressed tag sequence. This result indicated that using expressed tag sequences as leading sequences could promote LMW-GS and gliadin genes to be well expressed in E. coli. Further transcriptional analysis by quantitative real-time PCR (qRT-PCR) showed transcription levels of recombination genes (e.g. GST-Glutenin, His-S-Glutenin and SP(∗)-His-Glutenin) were 4-fold to 33-fold higher than those of the LMW-GS genes, which suggested these expressed tag sequences might play an important role in stimulating transcription. The possible molecular mechanism under this phenomenon was discussed.