One-step cell biomanufacturing platform:porous gelatin microcarrier beads promote human embryonic stem cell-derived midbrain dopaminergic progenitor cell differentiation in vitro and survival after transplantation in vivo

Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.

Human pluripotent stem cell-derived kidney organoids:Current progress and challenges

Human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal kidney.However,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogenesis and lack of a corticomedullary definition,uniform vascular system,and coordinated exit path-way for urinary filtrate.Therefore,further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development,regeneration,disease modeling,and drug screening.In this review,we discussed recent advances in the generation of hPSC-derived kidney organoids,how these organoids contribute to the understanding of human kidney development and research in disease modeling.Additionally,the limitations,future research focus,and applications of hPSC-derived kidney organoids were highlighted.

Current status of liver transplantation for human immunodeficiency virus-infected patients in China's Mainland

According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 cases.The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in China.In addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly affected.This often leads to the development of end-stage liver and kidney diseases.Therefore,organ transplantation has emerged as an important part of active treatment for HIV infected patients.However,the curative effect is not satisfactory.HIV infection has been considered a contraindication for organ transplantation.Until the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively inhibited.With prolonged survival,the failure of important organs has become the main cause of death among HIV patients.Therefore,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion.This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land China.To date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have survived.Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary complications.

Side Event"Human Rights Protection for the Next Generation:the Rights of Children and Youth"Held in Geneva

On January 23,as the UN Human Rights Council's Universal Periodic Review Working Group conducted its fourth review of China's human rights record,the side event"Human Rights Protection for the Next Generation:the Rights of Children and Youth",co-sponsored by the New Sunshine Charity Foundation and China NGO Network for International Exchanges,was held in Geneva.Experts and scholars representing dozens of civil society organisations from different countries exchanged their views around the topic.

Self-assembly of differentiated dental pulp stem cells facilitates spheroid human dental organoid formation and prevascularization

BACKGROUND The self-assembly of solid organs from stem cells has the potential to greatly expand the applicability of regenerative medicine.Stem cells can self-organise into microsized organ units,partially modelling tissue function and regeneration.Dental pulp organoids have been used to recapitulate the processes of tooth development and related diseases.However,the lack of vasculature limits the utility of dental pulp organoids.AIM To improve survival and aid in recovery after stem cell transplantation,we demonstrated the three-dimensional(3D)self-assembly of adult stem cell-human dental pulp stem cells(hDPSCs)and endothelial cells(ECs)into a novel type of spheroid-shaped dental pulp organoid in vitro under hypoxia and conditioned medium(CM).METHODS During culture,primary hDPSCs were induced to differentiate into ECs by exposing them to a hypoxic environment and CM.The hypoxic pretreated hDPSCs were then mixed with ECs at specific ratios and conditioned in a 3D environment to produce prevascularized dental pulp organoids.The biological characteristics of the organoids were analysed,and the regulatory pathways associated with angiogenesis were studied.RESULTS The combination of these two agents resulted in prevascularized human dental pulp organoids(Vorganoids)that more closely resembled dental pulp tissue in terms of morphology and function.Single-cell RNA sequencing of dental pulp tissue and RNA sequencing of Vorganoids were integrated to analyse key regulatory pathways associated with angiogenesis.The biomarkers forkhead box protein O1 and fibroblast growth factor 2 were identified to be involved in the regulation of Vorganoids.CONCLUSION In this innovative study,we effectively established an in vitro model of Vorganoids and used it to elucidate new mechanisms of angiogenesis during regeneration,facilitating the development of clinical treatment strategies.

An Exploration of the Three Dimensions and Epochal Strengths of Building a Human Community With a Shared Future

The idea of a human community with a shared future was proposed by the Communist Party of China(CPC)Central Committee with Comrade Xi Jinping at its core for the future development of human beings to face up to the most important question in today's world:“What is happening to the world and what should we do?”It profoundly answers the question of the world,history,and the times.The theory of a human community with a shared future is an innovative theory with a multidimensional formation logic that guides humanity toward continually seeking common interests and values.This paper dives into the profound motivations behind building a human community with a shared future from historical,cultural,and practical dimensions and analyzes its epochal value from both domestic and international perspectives.This not only helps exert China's role in the international community,contributing Chinese strength to the construction of a peaceful,stable,and prosperous human society,but also enhances the influence of the idea of a human community with a shared future in the international community,accelerating the building of a human community with a shared future that considers the legitimate concerns of all countries,and aiding in solving the crises facing the world.

Correlation analysis of human papillomavirus E6/E7 mRNA detection with diagnosis,prognosis and recurrence risk in patients with cervical epithelioma

BACKGROUND Cervical intraepithelial neoplasia(CIN)is an important precursor of cervical cancer.Early detection and treatment can reduce the incidence of cervical cancer.AIM To investigate the detection rate of human papillomavirus(HPV)E6/E7 mRNA in cervical tissue of patients with different types of epithelial cell neoplasia(CIN)and its relationship with CIN progression and diagnosis.METHODS One hundred women with HPV infection detected by cervical exfoliation cytology between January 2022 and January 2023 were retrospectively selected.These patients were graded CIN based on colposcopy and cervical pathology.The positive expression rates of HPV E6/E7 mRNA and HPV[polymerase chain reaction(PCR)-reverse dot crossing]were compared among all groups.Patients with HPV E6/E7 mRNA expression in the grade 1 CIN group were followed up for 1 yr.The relationship between atypical squamous epithelium and high malignant epithelial neoplasia was investigated by univariate and multivariate analysis.RESULTS The diagnostic sensitivity,specificity,and sensitivity of PCR-reverse point hybrid ization technology for secondary CIN were 70.41%,70.66%,and 0.714,respectively.Sensitivity and specificity for secondary CIN were 752%and 7853%,respectively,the area under the curve value was 0.789.Logistic Multifactorial model analysis revealed that the HPV positive rates and the HPV E6/E7 mRNA positive rates were independent risk factors of CIN grade I(P<0.05).In CIN grade I patients with positive for HPV E6/E7 mRNA,in its orientation to grade CIN patients,in its orientation to grade CIN patients,at 69.2%,compared with patients negative for HPV E6/E7 mRNA(30.8%),significant difference(P<0.05).CONCLUSION HPV E6/E7 mRNA and HPV(PCR-reverse dot hybrid)positive expression have a close relationship with CINgrade disease progression and is an independent risk factor for high-grade CIN lesions.

Unveiling Global Human Trafficking Trends: A Comprehensive Analysis

This paper presents a comprehensive analysis of global human trafficking trends over a twenty-year period, leveraging a robust dataset from the Counter Trafficking Data Collaborative (CTDC). The study unfolds in a systematic manner, beginning with a detailed data collection phase, where ethical and legal standards for data usage and privacy are strictly observed. Following collection, the data undergoes a rigorous preprocessing stage, involving cleaning, integration, transformation, and normalization to ensure accuracy and consistency for analysis. The analytical phase employs time-series analysis to delineate historical trends and utilizes predictive modeling to forecast future trajectories of human trafficking using the advanced analytical capabilities of Power BI. A comparative analysis across regions—Africa, the Americas, Asia, and Europe—is conducted to identify and visualize the distribution of human trafficking, dissecting the data by victim demographics, types of exploitation, and duration of victimization. The findings of this study not only offer a descriptive and predictive outlook on trafficking patterns but also provide insights into the regional nuances that influence these trends. The article underscores the prevalence and persistence of human trafficking, identifies factors contributing to its evolution, and discusses the implications for policy and law enforcement. By integrating a methodological approach with quantitative analysis, this research contributes to the strategic planning and resource allocation for combating human trafficking. It highlights the necessity for continued research and international cooperation to effectively address and mitigate this global issue. The implications of this research are significant, offering actionable insights for policymakers, law enforcement, and advocates in the ongoing battle against human trafficking.

Countermeasures and Suggestions for Strengthening Human Resource Management in China’s Pharmaceutical Industry

Objective To provide reference and enlightenment for the development of human resource management in China’s pharmaceutical industry and to put forward some suggestions to promote the further development of pharmaceutical industry.Methods The method of literature review was used to analyze the current situation and existing problems of human resource management in China’s pharmaceutical industry.Results and Conclusion Only by continuously improving the human resource management skills and innovating management methods can pharmaceutical enterprises achieve long-term benefits with sustainable development.The formulation of human resource management strategy in pharmaceutical industry must be conducive to the realization of the business goals of enterprises.To achieve this overall goal,the human resources management department of enterprises must make the plan from a strategic perspective,formulate talent strategic planning which serves the overall strategic goal of the enterprise.As a result,human resource management will play an important role in the development of China’s pharmaceutical industry.

Exploring the Digital Path of Human Resource Management in Innovation and Entrepreneurship Enterprises

The digitization of human resource management functions can enhance the adaptability of human resource management and promote the comprehensive digital development of innovative and entrepreneurial enterprises.This article first summarizes and evaluates the connotation and research status of the digitalization of enterprise human resource management.Secondly,it analyzes the influencing factors of digitalization of human resource management in innovative and entrepreneurial enterprises from three aspects:employee factors,organizational factors,and technological factors.Finally,it designs a digitalization plan for human resource management in innovative and entrepreneurial enterprises from four aspects:analyzing the current situation,preparing thoroughly,designing plans,and building systems.It emphasizes the value of digitalization of enterprise human resource management for innovative and entrepreneurial enterprises.

Knowledge and awareness of human mpox infection among healthcare workers:A cross-sectional study in southwestern Nigeria

Objective:To identify the knowledge and awareness level of human mpox viral infection among healthcare workers in southwestern Nigeria.Methods:A cross-sectional study was conducted in Ekiti State,southwest Nigeria among 316 healthcare workers that were selected through a systematic random sampling.Data were collected with the aid of a semi-structured,self-administered questionnaire.The Chi-square test and binary logistic regression were used to find the association between the independent and dependent variables.The significance level was set at P-value<0.05.Results:Two hundred and twenty-two(70.3%)of the respondents were aged≤40 years,mean age(36±9)years,189(59.8%)were female,306(96.8%)were Christians,and 203(64.2%)were married.Three hundred and fourteen(99.4%)of the respondents were aware of mpox infection.Main sources of information about mpox were medical education(44.0%),radio/television(32.0%)and newspaper(21.0%).However,among those aware of the disease,209(67.0%)demonstrated poor knowledge levels.Longer than 5 years’experience of medical practice was the only significant predictor of higher knowledge level of the disease(OR 1.76,95%CI 1.01-3.06;P=0.046).Conclusions:Despite the high awareness level of mpox infection among healthcare workers,there still exists a huge knowledge gap.It is recommended that targeted intervention could be directed towards continuous medical education and simulation exercises on re-emerging infectious diseases like mpox to improve the knowledge of the healthcare workers.

Zinc enhances the cell adhesion,migration,and self-renewal potential of human umbilical cord derived mesenchymal stem cells

BACKGROUND Zinc(Zn)is the second most abundant trace element after Fe,present in the human body.It is frequently reported in association with cell growth and proliferation,and its deficiency is considered to be a major disease contributing factor.AIM To determine the effect of Zn on in vitro growth and proliferation of human umbilical cord(hUC)-derived mesenchymal stem cells(MSCs).METHODS hUC-MSCs were isolated from human umbilical cord tissue and characterized based on immunocytochemistry,immunophenotyping,and tri-lineage differentiation.The impact of Zn on cytotoxicity and proliferation was determined by MTT and Alamar blue assay.To determine the effect of Zn on population doubling time(PDT),hUC-MSCs were cultured in media with and without Zn for several passages.An in vitro scratch assay was performed to analyze the effect of Zn on the wound healing and migration capability of hUC-MSCs.A cell adhesion assay was used to test the surface adhesiveness of hUC-MSCs.Transcriptional analysis of genes involved in the cell cycle,proliferation,migration,and selfrenewal of hUC-MSCs was performed by quantitative real-time polymerase chain reaction.The protein expression of Lin28,a pluripotency marker,was analyzed by immunocytochemistry.RESULTS Zn at lower concentrations enhanced the rate of proliferation but at higher concentrations(>100μM),showed concentration dependent cytotoxicity in hUC-MSCs.hUC-MSCs treated with Zn exhibited a significantly greater healing and migration rate compared to untreated cells.Zn also increased the cell adhesion rate,and colony forming efficiency(CFE).In addition,Zn upregulated the expression of genes involved in the cell cycle(CDC20,CDK1,CCNA2,CDCA2),proliferation(transforming growth factorβ1,GDF5,hypoxia-inducible factor 1α),migration(CXCR4,VCAM1,VEGF-A),and self-renewal(OCT4,SOX2,NANOG)of hUC-MSCs.Expression of Lin28 protein was significantly increased in cells treated with Zn.CONCLUSION Our findings suggest that zinc enhances the proliferation rate of hUC-MSCs decreasing the PDT,and maintaining the CFE.Zn also enhances the cell adhesion,migration,and self-renewal of hUC-MSCs.These results highlight the essential role of Zn in cell growth and development.

Risk Assessment of Human Exposure to 2-Methylnaphthalene, Phenanthrene and Didodecylphthalate via Consumption of Shrimps (Macrobrachium vollenhovenii) from Qua Iboe River Estuary, South-South Nigeria

Ibeno, one of the major oil producing communities in South-South Nigeria is a coastal commercial fishery hub that houses Axon-Mobil operational base and pharmaceutical/plastic industries. Shrimp species (Macrobrachium vollenhovenii) is a major aquatic food frequently consumed by inhabitants of the coastal area and those living hinterland, thus, being a major route of human exposure to 2-methylnaphthalene, phenanthrene and didodecyl phthalate in the area. The purpose of the study was to evaluate factors that determine bioaccumulation and assess the potential cancer and non-cancer risk posed by these contaminants through human (adult and children) exposure via shrimp’s consumption using gas chromatography-mass spectroscopy. The associated sediment showed higher mean concentrations of 2-methylnaphthalene, phenanthrene and didodecylphthalate at the two sites relative to those in fresh shrimp samples and factors such as size, lipid content, physicochemical property and environmental condition influenced the uptake of these contaminants. Besides water loss, the traditional drying process enhanced the levels of phenanthrene and didodecylphthalate in dry shrimps most likely due to combustion process and relatively low volatility, respectively and lowered the level of 2-methylnapthalene linked to its relatively high volatility. The potential of cancer and non-cancer development in human were highest via dry large shrimp consumption and followed the sequence: dry small shrimp > fresh large shrimp > fresh small shrimp and were within the USEPA reference standards. Although children were more vulnerable, the exposed individuals may not exhibit notable health-associated adverse effects in the near future. Thus, adequate advocacy is needed to sensitize those living in the catchments who often prefer dry shrimp in their meals on the adverse health implications of these contaminants for their survival and the need to maintain the health of the ecosystem.

Therapeutic utility of human umbilical cord-derived mesenchymal stem cells-based approaches in pulmonary diseases:Recent advancements and prospects

Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues worldwide.For diverse disease con-ditions,the currently available approaches are focused on alleviating clinical symptoms and delaying disease progression but have not shown significant therapeutic effects in patients with lung diseases.Human umbilical cord-derived mesenchymal stem cells(UC-MSCs)isolated from the human UC have the capacity for self-renewal and multilineage differentiation.Moreover,in recent years,these cells have been demonstrated to have unique advantages in the treatment of lung diseases.We searched the Public Clinical Trial Database and found 55 clinical trials involving UC-MSC therapy for pulmonary diseases,including coronavirus disease 2019,acute respiratory distress syndrome,bron-chopulmonary dysplasia,chronic obstructive pulmonary disease,and pulmonary fibrosis.In this review,we summarize the characteristics of these registered clinical trials and relevant published results and explore in depth the challenges and opportunitiesfaced in clinical application.Moreover,the underlying mole-cular mechanisms involved in UC-MSC-based therapy for pulmonary diseases are also analyzed in depth.In brief,this comprehensive review and detailed analysis of these clinical trials can be expected to provide a scientific reference for future large-scale clinical application.

Humanβ-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long noncoding RNA TCONS_00014506

BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of cancer cells.Long non-coding RNAs(lncRNAs)are involved in the process of cell differentiation and growth.AIM To investigate the effect of hBD-1 on the mammalian target of rapamycin(mTOR)pathway and autophagy in human colon cancer SW620 cells.METHODS CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration.Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation.Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway.Additionally,p-mTOR(Ser2448),Beclin1,and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis.RESULTS hBD-1 inhibited the proliferative ability of SW620 cells,as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1.hBD-1 decreased the expression of p-mTOR(Ser2448)protein and increased the expression of Beclin1 and LC3II/I protein.Furthermore,bioinformatics analysis identified seven lncRNAs(2 upregulated and 5 downregulated)related to the mTOR pathway.The lncRNA TCONS_00014506 was ultimately selected.Following the inhibition of the lncRNA TCONS_00014506,exposure to hBD-1 inhibited p-mTOR(Ser2448)and promoted Beclin1 and LC3II/I protein expression.CONCLUSION hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.

Preferences for oral-vs blood-based human immunodeficiency virus self-testing:A scoping review of the literature

BACKGROUND The evidence on preferences for oral-vs blood-based human immunodeficiency virus self-testing(HIVST)has been heterogenous and inconclusive.In addition,most evaluations have relied on hypothetical or stated use cases using discreet choice experiments rather than actual preferences among experienced users,which are more objective and critical for the understanding of product uptake.Direct head-to-head comparison of consumer preferences for oral-versus bloodbased HIVST is lacking.AIM To examine the existing literature on preferences for oral-vs blood-based HIVST,determine the factors that impact these preferences,and assess the potential implications for HIVST programs.METHODS Databases such as PubMed,Medline,Google Scholar,and Web of Science were searched for articles published between January 2011 to October 2022.Articles must address preferences for oral-vs blood-based HIVST.The study used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist to ensure the quality of the study.RESULTS The initial search revealed 2424 records,of which 8 studies were finally included in the scoping review.Pooled preference for blood-based HIVST was 48.8%(9%-78.6%),whereas pooled preference for oral HIVST was 59.8%(34.2%-91%)across all studies.However,for male-specific studies,the preference for blood-based HIVST(58%-65.6%)was higher than that for oral(34.2%-41%).The four studies that reported a higher preference for blood-based HIVST were in men.Participants considered blood-based HIVST to be more accurate and rapid,while those with a higher preference for oral HIVST did so because these were considered non-invasive and easy to use.CONCLUSION Consistently in the literature,men preferred blood-based HIVST over oral HIVST due to higher risk perception and desire for a test that provides higher accuracy coupled with rapidity,autonomy,privacy,and confidentiality,whereas those with a higher preference for oral HIVST did so because these were considered non-invasive and easy to use.Misinformation and distrust need to be addressed through promotional messaging to maximize the diversity of this new biomedical technology.

BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for>10 passages.Investigations of the role BMPRⅡplays in spinal cord development have primarily relied upon mouse and rat models,with interpolations to human development being derived through inference.Because of significant species differences between murine biology and human,including anatomical dissimilarities in central nervous system(CNS)structure,the findings made in murine models cannot be presumed to apply to human spinal cord development.For these reasons,our human in vitro model offers a novel tool to better understand neurodevelopmental pathways,including BMP signaling,as well as spinal cord injury research and testing drug therapies.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Human umbilical cord mesenchymal stem cell-derived exosomes loaded into a composite conduit promote functional recovery after peripheral nerve injury in rats

Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue regeneration.In previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal regeneration.This three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)tube.However,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains unknown.In this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived exosomes.Repair effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in rats.The results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft transplantation.More CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve reconnection.Therefore,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.

Unveiling the Dynamic World of Human Macrophage Specification during Prenatal Development

Researchers led by Prof.LI Hanjie from the Shenzhen Institute of Advanced Technology(SIAT)of the Chinese Academy of Sciences have unveiled the dynamics of human macrophage specification across 19 different tissues from early embryonic stages.The study was published in Cell on September 12.