The origin, transmission and clinical therapies on coronavirus disease 2019(COVID-19) outbreak——an update on the status

An acute respiratory disease,caused by a novel coronavirus(SARS-CoV-2,previously known as 2019-nCoV),the coronavirus disease 2019(COVID-19)has spread throughout China and received worldwide attention.On 30 January 2020,World Health Organization(WHO)officially declared the COVID-19 epidemic as a public health emergency of international concern.The emergence of SARS-CoV-2,since the severe acute respiratory syndrome coronavirus(SARSCoV)in 2002 and Middle East respiratory syndrome coronavirus(MERS-CoV)in 2012,marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century.As of 1 March 2020,a total of 87,137 confirmed cases globally,79,968 confirmed in China and 7169 outside of China,with 2977 deaths(3.4%)had been reported by WHO.Meanwhile,several independent research groups have identified that SARS-CoV-2 belongs toβ-coronavirus,with highly identical genome to bat coronavirus,pointing to bat as the natural host.The novel coronavirus uses the same receptor,angiotensin-converting enzyme 2(ACE2)as that for SARS-CoV,and mainly spreads through the respiratory tract.Importantly,increasingly evidence showed sustained human-tohuman transmission,along with many exported cases across the globe.The clinical symptoms of COVID-19 patients include fever,cough,fatigue and a small population of patients appeared gastrointestinal infection symptoms.The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes,which may be associated with acute respiratory distress syndrome(ARDS)and cytokine storm.Currently,there are few specific antiviral strategies,but several potent candidates of antivirals and repurposed drugs are under urgent investigation.In this review,we summarized the latest research progress of the epidemiology,pathogenesis,and clinical characteristics of COVID-19,and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.

Current evidence and challenges of systematic therapies for adult recurrent glioblastoma: Results from clinical trials

Recurrence is a major concern for adult patients with glioblastomas(GBMs), and the prognosis remains poor.Although several therapies have been assessed, most of them have not achieved satisfactory results. Therefore, there is currently no standard treatment for adult recurrent GBM(r GBM). Here, we review the results of clinical trials for the systematic therapy of r GBM. Regorafenib, rindopepimut and neoadjuvant programmed death 1(PD-1)inhibitors are promising agents for r GBM, while regorafenib is effective in both O6-methylguanine DNA methyltransferase(MGMT) promoter methylated and unmethylated patients. Temozolomide rechallenge and alkylating agents combined with bevacizumab can be useful for patients with MGMT methylation, and patients with isocitrate dehydrogenase(IDH) mutations or second recurrence can benefit from vocimagene amiretrorepvec(Toca511). Some phase I trials on targeted therapy and immunotherapy have shown positive results, and results from further studies are expected. In addition to the analysis of existing clinical trial results, forthcoming trials should be well designed, and patients are encouraged to participate in appropriate clinical trials.

Gynecological malignancies and hormonal therapies: Clinical management and recommendations

Every year in the world a large number of women receive a diagnosis of gynecological cancer and undergo a therapy such as surgery, chemotherapy and radiotherapy to the pelvic region. A large portion of these patients are already in menopause, but for younger patients therapies are responsible of early menopause. The physical and psychological symptoms due to iatrogenic menopause significantly reduce the quality of life; however hormone replacement therapy(HRT) has a high efficacy in reducing menopausal symptoms. The prescription of HRT in patients with story of gynecological cancer is debated because its safety has not been completely proven. The main criticism is based on the theory that the hormone replacement could stimulate growth of residual cancer cells increasing the risk of recurrence.

Decellularized extracellular matrix biomaterials for regenerative therapies:Advances,challenges and clinical prospects

Tissue engineering and regenerative medicine have shown potential in the repair and regeneration of tissues and organs via the use of engineered biomaterials and scaffolds.However,current constructs face limitations in replicating the intricate native microenvironment and achieving optimal regenerative capacity and functional recovery.To address these challenges,the utilization of decellularized tissues and cell-derived extracellular matrix(ECM)has emerged as a promising approach.These biocompatible and bioactive biomaterials can be engineered into porous scaffolds and grafts that mimic the structural and compositional aspects of the native tissue or organ microenvironment,both in vitro and in vivo.Bioactive dECM materials provide a unique tissue-specific microenvironment that can regulate and guide cellular processes,thereby enhancing regenerative therapies.In this review,we explore the emerging frontiers of decellularized tissue-derived and cell-derived biomaterials and bio-inks in the field of tissue engineering and regenerative medicine.We discuss the need for further improvements in decellularization methods and techniques to retain structural,biological,and physicochemical characteristics of the dECM products in a way to mimic native tissues and organs.This article underscores the potential of dECM biomaterials to stimulate in situ tissue repair through chemotactic effects for the development of growth factor and cell-free tissue engineering strategies.The article also identifies the challenges and opportunities in developing sterilization and preservation methods applicable for decellularized biomaterials and grafts and their translation into clinical products.

Second line systemic therapies for hepatocellular carcinoma: Reasons for the failure

Hepatocellular carcinoma(HCC) is the main cause of death in patients with cirrhosis, with an increasing incidence worldwide. Sorafenib is the choice therapy for advanced HCC. Over time several randomized phase Ⅲ trials have been performed testing sunitinib, brivanib, linifanib and other molecules in head-tohead comparison with Sorafenib as first-line treatment for advanced-stage HCC, but none of these has so far been registered in this setting. Moreover, another feared vacuum arises from the absence of molecules registered as second-line therapy for patients who have failed Sorafenib, representing an urgent unmet medical need. To date all molecules tested as second-line therapies for advanced hepatocellular carcinoma, failed to demonstrate an increased survival compared to placebo. What are the possible reasons for the failure? What we should expect in the near future?

Development of targeted therapies in treatment of glioblastoma

Glioblastoma （GBM） is a type of tumor that is highly lethal despite maximal therapy. Standard therapeutic approaches provide modest improvement in progression-free and overall survival, necessitating the investigation of novel therapies. Oncologic therapy has recently experienced a rapid evolution toward ＂targeted therapy＂, with drugs directed against specific targets which play essential roles in the proliferation, survival, and invasiveness of GBM cells, including numerous molecules involved in signal transduction pathways. Inhihitors of these molecules have already entered or are undergoing clinical trials. However, significant challenges in their development remain because several preclinical and clinical studies present conflicting results. In this article, we will provide an up-to-date review of the current targeted therapies in GBM.

Combining chemotherapy and targeted therapies in metastatic colorectal cancer

Colorectal cancer remains one of the major causes of cancer death worldwide. During the past years, the development of new effective treatment options has led to a considerable improvement in the outcome of this disease. The advent of agents such as capecitabine, irinotecan, oxaliplatin, cetuximab and bevacizumab has translated into median survival times in the range of 2 years. Intense efforts have focused on identifying novel agents targeting specific growth factor receptors, critical signal transduction pathways or mediators of angiogenesis. In addition, several clinical trials have suggested that some of these molecularly targeted drugs can be safely and effectively used in combination with conventional chemotherapy. In this article we review various treatment options combining cytotoxic and targeted therapies currently available for patients with metastatic colorectal cancer.

Modulating microRNAs in cancer: next-generation therapies

MicroRNAs(miRNAs)are a class of endogenously expressed non-coding regulators of the genome with an ability to mediate a variety of biological and pathological processes.There is growing evidence demonstrating frequent dysregulation of microRNAs in cancer cells,which is associated with tumor initiation,development,migration,invasion,resisting cell death,and drug resistance.Studies have shown that modulation of these small RNAs is a novel and promising therapeutic tool in the treatment of a variety of diseases,especially cancer,due to their broad influence on multiple cellular processes.However,suboptimal delivery of the appropriate miRNA to the cancer sites,quick degradation by nucleases in the blood circulation,and off target effects have limited their research and clinical applications.Therefore,there is a pressing need to improve the therapeutic efficacy of miRNA modulators,while at the same time reducing their toxicities.Several delivery vehicles for miRNA modulators have been shown to be effective in vitro and in vivo.In this review,we will discuss the role and importance of miRNAs in cancer and provide perspectives on currently available carriers for miRNA modulation.We will also summarize the challenges and prospects for the clinical translation of miRNAbased therapeutic strategies.

Potential of transposon-mediated cellular reprogramming towards cell-based therapies

Induced pluripotent stem(iPS)cells present a seminal discovery in cell biology and promise to support innovative treatments of so far incurable diseases.To translate iPS technology into clinical trials,the safety and stability of these reprogrammed cells needs to be shown.In recent years,different non-viral transposon systems have been developed for the induction of cellular pluripotency,and for the directed differentiation into desired cell types.In this review,we summarize the current state of the art of different transposon systems in iPS-based cell therapies.

Application of Radiopharmaceuticals in Targeted Tumor Therapies

Radiopharmaceutical therapy uses tumor-targeting carriers to deliver cytotoxic radioactivity to tumor tissues,selectively killing tumor cells,and thus producing minimal toxic and side e ects on surrounding healthy tissues^([1]).The use of radiopharmaceuticals to treat tumor has become one of the important ways of tumor therapy,and has made great progress in the basic research and clinical application of tumor therapy.

Is nutritional status a new indicator to use in clinical practice for colorectal cancer patients?

In this editorial we comment on the interesting article by Liu et al.The topic of discussion is the need for a cost-effective and easy-to-use scoring system for predicting the prognosis of colorectal cancer patients.In this context,nutritional assessment plays a crucial role in the multimodal evaluation of patients.In particular,the controlling nutritional status score was found to be an effective tool in the clinical decision-making process,in order to customize treatment strategies and to improve patient outcomes.

基于Clinical Trials数据库的癌性疼痛治疗药物临床试验分析

目的了解近年来癌性疼痛(癌痛)治疗药物临床试验的趋势和特点,为癌痛治疗药物的开发和临床研究提供参考依据。方法从Clinical Trials数据库中检索1987—2022年癌痛治疗药物临床试验的相关信息,从试验类型、备案时间、申报地区、癌痛类型、癌痛治疗药物等角度进行描述性分析。结果筛选出临床试验376项,由研究者发起的试验(IIT)项目数多于注册类试验(IST),其中北美洲的总项目数、IIT和IST项目数最多;试验总项目数和IST项目数先增长后回落,IIT的试验项目数稳步增长。针对慢性癌痛、爆发性癌痛和重度癌痛的研究相对较多。研究对象以阿片类药物尤其是芬太尼的占比最高。结论癌痛治疗药物临床试验对推进癌痛治疗药物治疗发挥了重要作用,未来有待进一步加强IST在新型癌痛治疗药物的研究和开展更多IIT研究,以更好地优化癌痛治疗效果。

Clinical characteristics of acute non-varicose upper gastrointestinal bleeding and the effect of endoscopic hemostasis

BACKGROUND Acute non-variceal upper gastrointestinal bleeding(ANVUGIB)constitutes a prevalent emergency within Gastroenterology,encompassing 80%-90%of all gastrointestinal hemorrhage incidents.This condition is distinguished by its abrupt onset,swift progression,and notably elevated mortality rate.AIM To gather clinical data from patients with ANVUGIB at our hospital in order to elucidate the clinical characteristics specific to our institution and analyze the therapeutic effectiveness of endoscopic hemostasis.METHODS We retrospectively retrieved the records of 532 patients diagnosed with ANVUGIB by endoscopy at our hospital between March 2021 and March 2023,utilizing our medical record system.Data pertaining to general patient information,etiological factors,disease outcomes,and other relevant variables were meticulously collected and analyzed.RESULTS Among the 532 patients diagnosed with ANVUGIB,the male-to-female ratio was 2.91:1,with a higher prevalence among males.Notably,43.6%of patients presented with black stool as their primary complaint,while 27.4%had hematemesis as their initial symptom.Upon admission,17%of patients exhibited both hematemesis and black stool,while most ANVUGIB patients primarily complained of overt gastrointestinal bleeding.Urgent routine blood examinations at admission revealed that 75.8%of patients had anemia,with 63.4%experiencing moderate to severe anemia,and 1.5%having extremely severe anemia(hemoglobin<30 g/L).With regard to etiology,53.2%of patients experienced bleeding without a definitive trigger,24.2%had a history of using gastric mucosa-irritating medications,24.2%developed bleeding after alcohol consumption,2.8%attributed it to improper diet,1.7%to emotional excitement,and 2.3%to fatigue preceding the bleeding episode.Drug-induced ANVUGIB was more prevalent in the elderly than middle-aged and young individuals,while bleeding due to alcohol consumption showed the opposite trend.Additionally,diet-related bleeding was more common among the young age group compared to the middle-aged group.Gastrointestinal endoscopy identified peptic ulcers as the most frequent cause of ANVUGIB(73.3%),followed by gastrointestinal malignancies(10.9%),acute gastric mucous lesions(9.8%),and androgenic upper gastrointestinal bleeding(1.5%)among inpatients with ANVUGIB.Of the 532 patients with gastrointestinal bleeding,68 underwent endoscopic hemostasis,resulting in an endoscopic treatment rate of 12.8%,with a high immediate hemostasis success rate of 94.1%.

Compare clinical efficacy and safety of neoadjuvant therapy and neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Meta-analysis

BACKGROUND To compare the efficacy and safety of total neoadjuvant therapy(TNT)and neoadjuvant chemoradiotherapy(nCRT)in the treatment of middle and low locally advanced rectal cancer.Our study will systematically collect and integrate studies to evaluate the ability of these two treatments to improve tumor shrinkage rates,surgical resection rates,tumor-free survival,and severe adverse events.AIM To provide clinicians and patients with more reliable treatment options to optimize treatment outcomes and quality of life for patients with locally advanced rectal cancer by comparing the advantages and disadvantages of the two treatment options.METHODS A full search of all clinical studies on the effectiveness and safety of TNT and nCRT for treating locally advanced rectal cancer identified in Chinese(CNKI,Wanfang,China Biomedical Literature Database)and English(PubMed,Embase)databases was performed.Two system assessors independently screened the studies according to the inclusion and exclusion criteria.Quality evaluation and RESULTS Finally,14 studies were included,six of which were randomized controlled studies.A total of 3797 patients were included,including 1865 in the TNT group and 1932 in the nCRT group.The two sets of baseline data were comparable.The results of the meta-analysis showed that the pCR rate[odds ratio(OR)=1.57,95%confidence interval(CI):1.30-1.90,P<0.00001],T stage degradation rate(OR=2.16,95%CI:1.63-2.57,P<0.00001),and R0 resection rate(OR=1.42,95%CI:1.09-1.85,P=0.009)were significantly greater in the nCRT group than in the nCRT group.There was no significant difference in the incidence of grade 3/4 acute toxicity or perioperative complications between the two groups.The 5-year OS[hazard ratio(HR)=0.84,95%CI:0.69-1.02,P=0.08]and DFS(HR=0.94,95%CI:0.03-1.39,P=0.74)of the TNT group were similar to those of the nCRT group.CONCLUSION TNT has greater clinical efficacy and safety than nCRT in the treatment of locally advanced rectal cancer.

Human dental pulp stem/stromal cells in clinical practice

Dental pulp stem/stromal cells(DPSCs)are fibroblast-like,neural crest-derived,and multipotent cells that can differentiate into several lineages.They are relatively easy to isolate from healthy and inflamed pulps,with little ethical concerns and can be successfully cryopreserved and thawed.The therapeutic effects of DPSCs derived from animal or human sources have been extensively studied through in-vitro and in-vivo animal experiments and the findings indicated that DPSCs are effective not only for dental diseases but also for systemic diseases.Understanding that translational research is a critical step through which the fundamental scientific discoveries could be translated into applicable diagnostics and therapeutics that directly benefit humans,several clinical studies were carried out to generate evidence for the efficacy and safety of autogenous or allogeneic human DPSCs(hDPSCs)as a treatment modality for use in cell-based therapy,regenerative medicine/dentistry and tissue engineering.In clinical medicine,hDPSCs were effective for treating acute ischemic stroke and human exfoliated deciduous teeth-conditioned medium(SHED-CM)repaired vascular damage of the corpus cavernous,which is the main cause of erectile dysfunction.Whereas in clinical dentistry,autologous SHED was able to rege-nerate necrotic dental pulp after implantation into injured teeth,and micrografts enriched with autologous hDPSCs and collagen sponge were considered a treatment option for human intrabony defects.In contrast,hDPSCs did not add a significant regenerative effect when they were used for the treatment of post-extraction sockets.Large-scale clinical studies across diverse populations are still lacking to provide robust evidence on the safety and efficacy of hDPSCs as a new treatment option for various human diseases including dental-related problems.

Clinical Application and Prospect of New Radiotherapy Technology in Cancer Treatment

Objective: Carbon ion therapy, a new radiotherapy technology, has shown its remarkable efficacy and potential in cancer treatment, especially in the treatment of refractory tumors. Methods: This paper clarifies the physical basis, technological change, and clinical practice effect of carbon ion therapy, comprehensively discusses the future prospects, and evaluates the clinical application effect. Results: The technology has significantly improved the treatment effectiveness and received a positive response from patients. Conclusion: Carbon ion therapy technology has become a major innovation in the field of cancer treatment. It not only has a profound impact on many current cancer therapy methods but also indicates the application blueprint for a wider range of cancer types in the future, showing a new chapter of medical technology advancement.

Knowledge and Attitudes of Knust Pre-Clinical Dental Students towards Orthodontic Treatment

Background: Orthodontics is a dental specialty focusing on correcting dental irregularities and malocclusion. Knowledge and attitudes towards orthodontic treatment are crucial for promoting oral health and overall well-being. Education and awareness play a vital role in ensuring optimal treatment outcomes and improving quality of life. Aim: This study aims to determine the knowledge and attitudes of Kwame Nkrumah University of Science and Technology (KNUST) pre-clinical dentistry students concerning orthodontic therapy. Methodology: This research is a quantitative descriptive cross-sectional study. The research used a non-random convenience sampling method to form the desired sample. For data collection, an interview-administered questionnaire was used over one month. The study set its sights on pre-clinical dental students in KNUST. A total of 150 questionnaires were printed to meet the sample size. Results: The results of the research showed that the knowledge level of KNUST pre-clinical students on orthodontic treatment and its nuances is quite limited. They however had a fair level of knowledge on the disease or ailment that orthodontic treatments solved (especially malocclusion). Their interest in orthodontic treatments on the other hand was quite significant, with a large number having interest in it. Conclusion: To conclude, KNUST pre-clinical students in Ghana although having a limited level of knowledge on orthodontic treatments have a keen interest in undergoing them regardless of the discomforts or the length of time.

Targeted therapies in gynecological cancers:a comprehensive review of clinical evidence

Advanced and recurrent gynecological cancers are associated with poor prognosis and lack of effective treatment.The developments of the molecular mechanisms on cancer progression provide insight into novel targeted therapies,which are emerging as groundbreaking and promising cancer treatment strategies.In gynecologic malignancies,potential therapeutic targeted agents include antiangiogenic agents,poly(ADP-ribose)polymerase(PARP)inhibitors,tumor-intrinsic signaling pathway inhibitors,selective estrogen receptor downregulators,and immune checkpoint inhibitors.In this article,we provide a comprehensive review of the clinical evidence of targeted agents in gynecological cancers and discuss the future implication.

Combination Therapies for Advanced Biliary Tract Cancer

Biliary tract cancers(BTCs)are a group of malignant neoplasms that have recently increased in incidence and have a poor prognosis.Surgery is the only curative therapy.However,most patients are only indicated for palliative therapy because of advanced-stage disease at diagnosis and rapid progression.The current first-line treatment for advanced BTC is gemcitabine and cisplatin chemotherapy.Nonetheless,many patients develop resistance to this regimen.Over the years,few chemotherapy regimens have managed to improve the overall survival of patients.Accordingly,novel therapies such as targeted therapy have been introduced to treat this patient population.Extensive research on tumorigenesis and the genetic profiling of BTC have revealed the heterogenicity and potential target pathways,such as EGFR,VEGF,MEK/ERK,PI3K and mTOR.Moreover,mutational analysis has documented the presence of IDH1,FGFR2,HER2,PRKACA,PRKACB,BRAF,and KRAS gene aberrations.The emergence of immunotherapy in recent years has expanded the treatment landscape for this group of malignancies.Cancer vaccines,adoptive cell transfer,and immune checkpoint inhibitors have been extensively investigated in trials of BTC.Therefore,patient stratification and a combination of various therapies have become a reasonable and important clinical strategy to improve patient outcomes.This review elaborates the literature on combined treatment strategies for advanced BTC from the past few years and ongoing clinical trials to provide new inspiration for the treatment of advanced BTC.

2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.