Anti-silencing function 1B knockdown suppresses the malignant phenotype of colorectal cancer by inactivating the phosphatidylinositol 3-kinase/AKT pathway

BACKGROUND Mounting studies have highlighted the pivotal influence of anti-silencing function 1B(ASF1B)on the malignancy of cancers.AIM To explore the influence and mechanism of ASF1B in colorectal cancer(CRC).METHODS Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect mRNA expression of ASF1B.Immunohistochemical staining was performed to detect protein expression of ASF1B and Ki67 in tumor tissues.Western blot analysis was used to determine levels of ASF1B and proliferation/epithelial mesenchymal transition(EMT)/stemness-related proteins.In addition,the proliferation of CRC cells was assessed using Cell Counting Kit-8 and 5-Ethynyl-2’-Deoxyuridine assays.The migration and invasion of CRC cells were evaluated using transwell assays.Stemness of CRC cells was tested using the sphere formation assay.To construct a xenograft tumor model,HCT116 cells were introduced into mouse flanks via subcutaneous injection.RESULTS ASF1B expression was markedly increased in CRC tissues and cells,and it was inversely correlated with overall survival of CRC patients and was positively associated with the tumor node metastasis(TNM)stage of CRC patients.Silencing of ASF1B suppressed proliferation,migration,invasion,stemness and EMT of CRC cells as well as tumorigenesis of xenograft mice.Furthermore,protein levels of Pphosphatidylinositol 3-kinase(p-PI3K)and p-AKT were decreased after silencing of ASF1B in CRC cells.The inhibitory effects of ASF1B knockdown on cell proliferation,stemness and EMT were partly abolished by PI3K activator in CRC cells.CONCLUSION Silencing of ASF1B inactivated the PI3K/AKT pathway to suppress CRC malignancy in vitro.

Foods that fight off cancer through anti-inflammation

Background Since the middle of the 19th century,German pathologist Rudolf Virchow proposed that tumors originate from chronic inflammation[1].At present,the medical community has determined that inflammation is closely related to the occurrence,development and efficacy of anti-cancer treatment[2].Recently,an“anti-inflammatory diet”that claims to have functions such as cancer prevention has attracted much attention.To unveil the magic of the“anti-inflammatory diet”,let’s start with the concept of inflammation,which is the core of the“anti-inflammatory diet”.

Chinese clinical practice guidelines for ultrasound-guided irreversible electroporation of liver cancer(version 2022)

Introduction Liver cancer remains a global health challenge,and its incidence is increasing worldwide.It is estimated that by 2025,more than one million individuals will be affected by liver cancer annually[1,2].In recent years,ablation has become a widely accepted treatment option for patients with primary and secondary liver malignancies[3].The commonly used ablation method for liver cancer is thermal ablation,including radiofrequency ablation.

Prediction of syphilis incident rate and number in China based on the GM(1,1)grey model

Objective:To explore the feasibility of using grey model GM(1,1)model to predict syphilis,and to provide a theoretical basis for the health sector to develop corresponding strategies.Methods:GM(1,1)model was used to construct and simulate the incident rate and case number of syphilis in China from 2009 to 2018 to predict the change trend.Results:The GM(1,1)prediction model of syphilis incident rate was x^(1)(k+1)=929.367901 e(0.029413k)-906.297901.The GM(1,1)prediction model for the number of syphilis patients was x^(1)(k+1)=1060.278025 e(0.034280k)-1029.639925.For syphilis incidence model,the posterior difference ratio was 0.19819 and the probability of small error was 1.For the syphilis incident number model,the posterior difference ratio was 0.18450 and the probability of small error was 1.The above models have good fitting accuracy with excellent grade level and can be predicted by extrapolation and predicted that the syphilis incidence in 2019-2021 may be 36.15 per 100,000,37.23 per 100,000 and 38.34 per 100,000,respectively.From 2019 to 2021,the number of incident syphilis cases in China may be 503,406,520,962 and 539,130,respectively.Conclusion:The GM(1,1)model can well fit and predict the change trend of syphilis incidence in time series.The prediction model showed that the incidence of syphilis may continue to increase and the number of syphilis cases per year may continue to increase substantially.More effort is needed to strengthen the prevention and treatment of venereal disease,reduce venereal harm to the population and improve the early detection rate of syphilis.

Gp350-anchored extracellular vesicles: promising vehicles for delivering therapeutic drugs of B cell malignancies

Although chimeric antigen receptor-modified(CAR)T cell therapy has been successfully applied in the treatment of acute B lymphocytic leukemia,its effect on Burkitt lymphoma(BL)and chronic B lymphocytic leukemia(B-CLL)is unsatisfactory.Moreover,fatal side effects greatly impede CAR T cell application.Extracellular vesicles(EVs)are excellent carriers of therapeutic agents.Nevertheless,EVs mainly accumulate in the liver when administered without modification.As an envelope glycoprotein of Epstein–Barr viruses,gp350 can efficiently bind CD21 on B cells.Here,gp350 was directly anchored onto red blood cell EVs(RBC-EVs)via its transmembrane region combined with low-voltage electroporation.The results showed that gp350 could anchor to RBC-EVs with high efficiency and that the resulting gp350-anchored RBC-EVs(RBC-EVs/gp350^(Etp))exhibited increased targeting to CD21+BL and B-CLL relative to RBC-EVs.After the loading of doxorubicin or fludarabine,RBC-EVs/gp350^(Etp) had powerful cytotoxicity and therapeutic efficacy on CD21+BL or B-CLL,respectively.Moreover,RBC-EVs/gp350^(Etp) loaded with a drug did not exhibit any apparent systemic toxicity and specifically induced the apoptosis of tumor B cells but not normal Bcells.Therefore,our findings indicate that drug-loaded RBC-EVs/gp350^(Etp) may be adopted in the treatment of CD21+B cell malignancies.

The incidence and prediction of tuberculosis in China

Objective:To explore the incidence trend of tuberculosis in China from 2009 to 2018,and make a short-term prediction,so as to provide reference for scientific formulation of prevention and control measures for tuberculosis and rational allocation of control and prevention resources.Methods:The grey model GM(1,1)model was used to build and predict the incidence of tuberculosis in China by extracting the data from 2009 to 2018 from the Statistical Yearbook of China.Results:The GM(1,1)prediction model was established to predict the incidence of tuberculosis.The GM(1,1)prediction model for tuberculosis incidence was x^(1)(k+1)=-2572.122087 e(-0.029096k)+2653.212087.The grey GM(1,1)prediction model for pulmonary tuberculosis case number was x^(1)(k+1)=-4092.009372 e(-0.024334k)+4199.703172.The above two models with high fitting accuracy were used to predict that the incidence of tuberculosis in 2019-2021 would be 56.77/100,000,55.14/100,000 and 53.56/100,000,respectively.The model predicted that the number of incident tuberculosis cases may be 790,242,771,245 and 752,704 from 2019 to 2021 in China,respectively.Conclusion:The projection shows that the incidence of tuberculosis may decrease,but the annual incident number of tuberculosis is still very high.We should continue to strengthen the prevention and standardized treatment of tuberculosis,and improve the early detection and treatment rates.

Systemic therapy in gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic interventions.Although surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after surgery.In recent years,targeted therapy has significantly improved the prognosis of patients with advanced GISTs.Imatinib mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this disease.However,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of treatment.Consequently,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug resistance.Immunotherapy has emerged as a potential approach for the treatment of advanced GISTs.This review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.

SR-BI expression regulates the gastric cancer tumor immune microenvironment and is associated with poor prognosis

Aim:Scavenger receptor class B,type I(SR-BI)is an integral plasma membrane protein that has been reported to be overexpressed in various malignancies,such as renal cancer,breast cancer,and prostate cancer,and is an independent prognostic factor.However,the clinical value and expression of SR-BI in GC are unknown.Our research aimed to explore the role of SR-BI in combination with immune markers as a diagnostic and prognostic marker for gastric cancer(GC).Methods:GC tissues,paracancerous tissues,and clinicopathological data of 149 patients were collected.The expression level of SR-BI,Tumor-infiltrating lymphocytes(TILs),and PD-L1 were evaluated by immunohistochemistry(IHC).The associations of the SR-BI staining intensity with clinicopathological features and immune markers were determined by the chi-square test.Univariate and multivariate COX regression analyses were used to evaluate independent prognostic factors.Kaplan–Meier analyses were performed to plot the survival curve.Results:Our results indicated that SR-BI was expressed at higher levels in tumor tissues than in adjacent paracancerous tissues(p<0.001),and patients with high levels of SR-BI expression had a worse prognosis.Univariate and multivariate analyses revealed that high SR-BI expression was an independent factor for poor prognosis.The chi-square test determined that the expression of SR-BI was negatively correlated with CD4+T cells and CD8+T cells(CD4+T cells,p=0.013;CD8+T cells,p=0.021),and positively correlated with PD-L1(p=0.022).Finally,survival analysis revealed that CD4+T cells were associated with the prognosis of GC patients(p=0.019),and the combined survival analysis of SR-BI and CD4+T cells was also statistically significant(p=0.030).Conclusion:SR-BI is highly expressed in GC tissue and associated with poor prognosis.Moreover,SR-BI can also regulate the GC tumor immune microenvironment.

National guidelines for diagnosis and treatment of gastric cancer 2022 in China(English version)

Contents 1.Overview 2.Diagnosis 2.1 Symptoms 2.2 Signs 2.3 Imaging 2.3.1 X-ray gas-barium double-contrast imaging 2.3.2 Ultrasonography(US)2.3.3 CT 2.3.4 MRI 2.3.5 Positron emission tomography(PET)-CT 2.3.6 Emission computed tomography(ECT)2.3.7 Tumor biomarkers。

Comments on National guidelines for diagnosis and treatment of gastric cancer 2022 in China(English version)

Gastric cancer is one of the most common malignancies in China.According to the latest statistics in 2020,the incidence and mortality of gastric cancer all rank the third among all cancers,which have brought a huge burden to people’s health and social economy.Besides the high morbidity and mortality,the low early diagnosis rate is another dilemma of gastric cancer in China.Early gastric cancer accounts for only 20%of new gastric cancer cases in China.Most cases are already in the advanced stage when discovered,and the overall 5-year survival rate is less than50%(1,2).Over the past decades,China has made great progress in the prevention and treatment of gastric cancer,but it is still a relatively prominent health problem.

Complete response of a locally advanced pulmonary hepatoid adenocarcinoma patient to perioperative XELOX-containing chemoimmunotherapy

With morphological features resembling hepatocellular carcinoma,hepatoid adenocarcinoma of the lung(HAL)is a rare and aggressive subtype of lung cancer with a 5-year survival of only 8%.1 Most HAL patients present increased serum alpha-fetoprotein(AFP)levels that are commonly related to poor prognosis.Most insights into HAL have come from case series or reports,and TP53 is frequently mutated in HAL.The heterogeneity of HAL complicates the diagnosis.With no established standard,the management of HAL is modeled on that of classical lung adenocarcinoma,although with dismal outcomes.2 Herein,we reported the effective management of a stage IIIb HAL patient with perioperative chemoimmunotherapy and curative-intent surgery.The patient remained disease-free and minimal residual disease(MRD)-negative for more than one year after surgery.

Recent progress of aptamer-drug conjugates in cancer therapy

Aptamers are single-stranded DNA or RNA sequences that can specifically bind with the target protein or molecule via specific secondary structures.Compared to antibody-drug conjugates(ADC),aptamer-drug conjugate(ApDC)is also an efficient,targeted drug for cancer therapy with a smaller size,higher chemical stability,lower immunogenicity,faster tissue penetration,and facile engineering.Despite all these advantages,several key factors have delayed the clinical translation of ApDC,such as in vivo off-target effects and potential safety issues.In this review,we highlight the most recent progress in the development of ApDC and discuss solutions to the problems noted above.

New insight into immune checkpoint inhibitors in the treatment of advanced renal cell carcinoma

Kidney cancer,accounting for 4%of all new cancer cases in men and 3%in women,is one of the ten most frequently diagnosed cancer types,of which renal cell carcinoma(RCC)is the most frequent kind of kidney cancer(responsible for70%of adult renal cancer cases).Before the development of immune checkpoint inhibitors(ICIs),RCC was considered an immunoreactive tumor and treated with IL-2 and other immunotherapies.

Development and Characterization of Nanobody-Derived CD47 Theranostic Pairs in Solid Tumors

Overexpression of CD47 is frequently observed in various types of human malignancies,inhibiting myeloidmediated elimination of tumor cells and affecting the prognosis of cancer patients.By mapping biomarker expression,immuno-positron emission tomography has been increasingly used for patient screening and response monitoring.By immunization alpacas with recombinant human CD47,we prepared a CD47-targeting nanobody C2 and developed[^(68)Ga]Ga-NOTA-C2,followed by an exploration of the diagnostic value in CD47-expressing tumor models including gastric-cancer patient-derived xenograft models.By fusing C2 to an albumin binding domain(ABD),we synthesized ABDC2,which had increased in vivo half-life and improved targeting properties.We further labeled ABDC2 with^(68)Ga/^(89)Zr/177Lu to develop radionuclide theranostic pairs and evaluated the pharmacokinetics and theranostic efficacies of the agents in cell-and patient-derived models.Both C2 and ABDC2 specifically reacted with human CD47 with a high KD value of 23.50 and 84.57 pM,respectively.[^(68)Ga]Ga-NOTA-C2 was developed with high radiochemical purity(99>%,n=4)and visualized CD47 expression in the tumors.In comparison to the rapid renal clearance and short half-life of[^(68)Ga]Ga-NOTA-C2,both[^(68)Ga]Ga-NOTA-ABDC2 and[^(89)Zr]Zr-DFOABDC2 showed prolonged circulation and increased tumor uptake,with the highest uptake of[^(89)Zr]Zr-DFO-ABDC2 occurring at 72 h post-injection.Moreover,[177Lu]Lu-DOTA-ABDC2 radioimmunotherapy suppressed the tumor growth but was associated with toxicity,warranting further optimization of the treatment schedules.Taken together,we reported a series of nanobody-derived CD47-targeted agents,of which[^(68)Ga]Ga-NOTA-C2 and[^(89)Zr]Zr-DFO-ABDC2 are readily translatable.Optimization and translation of CD47-targeted theranostic pair may provide new prospects for CD47-targeted management of solid tumors.

IR780/Gemcitabine-conjugated metal-phenolic network enhanced photodynamic cancer therapy

Photodynamic therapy (PDT) is a clinically approved cancer treatment that uses energy of light to generate active substances that cause damage to the cancer. Photosensitizers are employed to absorb light and generate toxic reactive oxygen species (ROS) to damage biomolecules like DNA. At the same time, some chemotherapy drugs like nucleotide analogues can provide mechanism-guided promotion in the treatment efficacy of PDT. However, the photosensitizer and chemotherapy drugs used in PDT is usually organic molecules, which suffers from bad solubility, fast clearance, and acute toxicity. To achieve targeted treatment, a reasonable delivery system is necessary. Therefore, we reported a metal-phenolic network where IR780 and gemcitabine were coupled chemically to overcome these shortcomings. The enhanced PDT effects can be realized by the promoted cell death both in vitro and in vivo. Moreover, the synergistic therapy also induced T-cell mediated anti-tumor immune response, which was significant for the inhibition of distant tumor growth. This work expanded the biomedical application of metal-phenolic materials and contribute to the wider application of photodynamic cancer therapy.

Surgery in platinum-resistant recurrent epithelial ovarian carcinoma

BACKGROUND Ovarian cancer is one of the three most common malignant tumors of the female reproductive tract and ranks first in terms of mortality among gynecological tumors.Epithelial ovarian carcinoma(EOC)is the most common ovarian malignancy,accounting for 90%of all primary ovarian tumors.The clinical value of cytoreductive surgery in patients with platinum-resistant recurrent EOC remains largely unclear.AIM To evaluate the feasibility of secondary cytoreductive surgery for treating platinum-resistant recurrent EOC.METHODS This was a retrospective study of the clinical data of patients with platinumresistant EOC admitted to the Cancer Hospital of the University of Chinese Academy of Sciences between September 2012 and June 2018.Patient baseline data were obtained from clinical records.Routine follow-up of disease progression was performed as follows.CA125 assessment and physical examination were performed every 3 wk during treatment,including gynecological examination.Imaging assessment was carried out every 12 wk by B-mode ultrasound,computed tomography,or magnetic resonance imaging.The primary outcome was progression-free survival(PFS).Secondary outcomes included overall survival(OS),chemotherapy-free interval(CFI),and complications.Follow-up ended on April 15,2019.RESULTS A total of 38 patients were included.R0 resection was achieved in 25(65.8%) patients and R1/2 in 13 (34.2%). Twenty-five (65.8%) patients required organ resection. Nine(23.7%) patients had operative complications, 36 (94.7%) received chemotherapy, and five (13.2%)had targeted therapy. Median PFS and OS were 10 (95%CI: 8.27-11.73) months and 28 (95%CI:12.75-43.25) months, respectively;median CFI was 9 (95%CI: 8.06-9.94) months. R0 resection andpostoperative chemotherapy significantly prolonged PFS and OS (all P < 0.05), and R0 resectionalso significantly prolonged CFI (P < 0.05). Grade ≥ 3 complications were observed, includingrectovaginal fistula (n = 1), intestinal and urinary fistulas (n = 1), and renal failure-associated death(n = 1). Except for the patient who died after surgery, all other patients with complications weresuccessfully managed. Two patients developed intestinal obstruction and showed improvementafter conservative treatment.CONCLUSIONSecondary cytoreductive surgery is feasible for treating platinum-resistant recurrent EOC. Thesefindings provide important references for the selection of clinical therapeutic regimens.

Outcome measures of phase III anticancer drug trials in China

To the Editor:Phase III clinical trials have been used to provide evidence in support of the approval of most new agents in the treatment of cancer.[1]The selection of the primary endpoint is critical to the outcome of phase III clinical trials and the launch of the cancer drug.In the present study,we performed a crosssectional study to describe the endpoint information and analyze the trends over time in the research and development of cancer drugs tested in phase III clinical trials in China.

Immunological effects of nano-enabled hyperthermia for solid tumors: opportunity and challenge

Compared to conventional hyperthermia that is limited by low selectivity and severe side effects,nano-enabled hyperthermia yields great potentials to tackle these limitations for cancer treatment.Another major advance is the observation of immunological responses associated with nano-enabled hyperthermia,which introduces a new avenue,allowing a potential paradigm shift from the acutely effective and cytotoxicity-centric response to the next-phase discovery,i.e.,long-lasting and/or systemic anti-tumor immunity.This perspective first discusses the temperature-gradient and the spatially-structured immunological landscape in solid tumors receiving nano-enabled hyperthermia.This includes the discussion about underlying mechanism such as immunogenic cell death,which initiates a profound immunological chain reaction.In order to propagate the immune activation as a viable therapeutic principle,we further discussed the tumor type-specific complexity in the immunological tumor microenvironment,including the creative design of nano-enabled combination therapy to synergize with nano-enabled hyperthermia.

Biosafety assessment of delivery systems for clinical nucleic acid therapeutics

Nucleic acid therapeutics,which involve transferring exogenous genes inside target cells,are a promising clinical treatment option that can regulate gene expression at the transcriptional or post-transcriptional level.Ideally,this kind of treatment modality will not lead to an unwanted immune response.Compared with traditional treatment methods,nucleic acid therapeutics can achieve prolonged and stable curative effects.As an emerging treatment method,nucleic acid therapeutics have played an increasingly important role in clinical settings for the treatment of various conditions,including infectious diseases,cancer,immune-related diseases,and monogenetic diseases.To date,a large number of clinical trials have been conducted,and more than 30 nucleic acid drugs have been approved,highlighting the strong potential of this approach in clinical practice.Diverse carriers are used to protect nucleic acids from being degraded and to help them reach their targets accurately.However,some carriers are known to cause negative effects on the release and expression of nucleic acid drugs as well as adverse effects such as allergic reactions and accumulation in the liver.Therefore,biosafety assessment of delivery systems before their application in clinical settings is critical.In this review,we describe different delivery systems for nucleic acid drugs and discuss their biosafety in both preclinical and clinical studies,with particular focus on the carriers themselves,drug administration method,and overall treatment of the disease.

Hydrogen-Bonding-Induced H-Aggregation of Charge-Transfer Complexes for Ultra-Efficient Second Near-Infrared Region Photothermal Conversion

Aggregation plays a critical role in modulating the photophysical process of organicmolecules.However,the rational control of the construction of a functionoriented stacking mode for efficient photothermal(PT)conversion in the second near-infrared region(NIR-II;1000-1700 nm)remains a challenge.Herein,an H-aggregation of 3,3′,5,5′-Tetramethylbenzidine(TMB)-TMB dication(TMB++)complexes in linear agarose(H-TTC/LAG)with narrowed band gap(0.96 eV)was fabricated through intermolecular hydrogenbonding interactions between the amino groups of TTC and the peripheral hydroxyl groups of LAG.Charge-transfer mechanism and H-aggregation ensured NIR-Ⅱ absorption of the complex at>1400 nm.The H-aggregation also promoted a non-radiation relaxation pathway and improved the thermal stability of TTC,which together favored the constructed H-TTC/LAG with ultra-efficient PT conversion that increased rapidly to 140℃ in 15 s under the NIR-Ⅱ laser(1064 nm,1.0 W cm^(−2))irradiation.Such a unique H-TTC/LAG with good biocompatibility was used to demonstrate a superior PT therapy via high-efficie ncy tumor growth inhibition in mouse mammary carcinoma(4T1)the BALB/c mice tumor-bearing xenografts.This is the first established H-aggregation of charge-transfer complexes in a noncovalent system,which not only provides a new strategy to develop ultra-efficient NIR-Ⅱ PT materials but also paves the way for constructing functional materials with aggregates of charge-transfer complexes.