Colorectal cancer(CRC) is a common malignant tumor worldwide. Due to the treatment intolerance and side effects, CRC rank the top among various cancers regarding the incidence and mortality rates. Therefore, exploring new therapies is of great significance for the treatment of CRC. Aerobic glycolysis(AEG) plays an important role in the microenvironment formation, proliferation, metastasis, and recurrence of CRC and other tumor cells. It has been confirmed that intervening in the AEG pathway can effectively curb CRC. The active ingredients and compound prescriptions of traditional Chinese medicine(TCM) can effectively inhibit the proliferation, metastasis, and drug resistance and regulate the apoptosis of tumor cells by modulating AEG-associated transport proteins [eg, glucose transporters(GLUT)], key enzymes [hexokinase(HK) and phosphofructokinase(PFK)], key genes [hypoxia-inducible factor 1(HIF-1) and oncogene(c-Myc)], and signaling pathways(MET/PI3K/Akt/mTOR). Accordingly, they can treat CRC, reduce the recurrence, and improve the prognosis of CRC. Although AEG plays a key role in the development and progression of CRC, the specific mechanisms are not yet fully understood. Therefore, this article delves into the intrinsic connection of the targets and mechanisms of the AEG pathway with CRC from the perspective of tumor cell glycolysis and explores how active ingredients(oxymatrine, kaempferol, and dioscin) and compound prescriptions(Quxie Capsules, Jiedu Sangen Decoction, and Xianlian Jiedu Prescription) of TCM treat CRC by intervening in the AEG pathway. Additionally, this article explores the shortcomings in the current research, aiming to provide reliable targets and a theoretical basis for treating CRC with TCM.
Humans ; Colorectal Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Glycolysis/drug effects* ; Animals ; Medicine, Chinese Traditional ; Signal Transduction/drug effects*

PURPOSE: Bone cement-reinforced fenestrated pedicle screws (FPSs) have been widely used in the internal fixation and repair of the spine with osteoporosis in recent years and show significant improvement in fixation strength and stability. However, compared with conventional reinforcement methods, the advantages of bone cement-reinforced FPSs remain undetermined. This article compares the effects of fenestrated and conventional pedicle screws (CPSs) combined with bone cement in the treatment of osteoporosis. METHODS: A clinical control study of FPSs and CPSs combined with bone cement reinforcement in osteoporotic vertebral internal fixation was performed using the database PubMed, Embase, Cochrane Library, CNKI, the Wanfang, and the China Biomedical Literature Service System. Two evaluators screened the relevant literature in strict accordance with the inclusion criteria (diagnosis of participants, type of clinical study, treatment with FPS and CPS, and outcome indicators) and exclusion criteria (duplicate literature and missing or incorrect data) and independently conducted data extraction and quality evaluation. Clinical control studies of direct comparison between FPS and CPS combined with bone cement reinforcement in patients who were definitively diagnosed with thoracolumbar fractures or spinal degenerative diseases were included. Quality evaluation was conducted using the Cochrane risk bias evaluation tool for randomized controlled studies and using the Newcastle-Ottawa scale for retrospective case-control studies. RevMan software (version 5.3) was used for the meta-analysis to compare the clinical efficacy, radiological results, and related complications of the 2 methods. RESULTS: A total of 13 articles were included, including 7 randomized controlled studies and 6 retrospective case-control studies. There were 909 patients in these studies, 451 in the FPS and polymethyl methacrylate (FPS & PMMA) group and 458 in the CPS and polymethyl methacrylate (CPS & PMMA) group. The results of the meta-analysis showed that there was no significant difference between the 2 groups in operation time, hospital stay, visual analogue score, Japanese orthopaedic association score, Oswestry disability index score, Cobb angle, vertebral body deformation index and fusion rate (p > 0.05). The mean difference of intraoperative bleeding volume was -10.45, (95% confidence intervals (CI) (-16.92, -3.98), p = 0.002), the mean difference of loss height of the anterior edge of the vertebral body after surgery was -0.69 (95% CI (-0.93, -0.44), p < 0.001), and the relative risk (RR) of overall complication rate was 0.43 (95% CI (0.27, 0.68), p < 0.001), including the RR of bone cement leakage rate was 0.57 (95% CI (0.39, 0.85), p = 0.005). The screw loosening rate (RR = 0.26, 95% CI (0.13, 0.54), p < 0.001) of the FPS group was significantly lower than that of the CPS group. CONCLUSION The existing clinical evidence shows that compared with the CPS combined with bone cement, the use of FPS repair in the internal fixation of an osteoporotic vertebral body can reduce the amount of intraoperative bleeding, be more conducive to maintaining the height of the vertebral body, and significantly reduce the incidence of postoperative complications such as bone cement leakage and screw loosening.
Humans ; Pedicle Screws ; Bone Cements ; Spinal Fractures/surgery* ; Osteoporotic Fractures/surgery* ; Fracture Fixation, Internal/instrumentation*

OBJECTIVE: To explore the construction method of a resistant multiple myeloma (MM) patient-derived xenotransplantation (PDX) model. METHODS: 1.0×10⁷ MM patient-derived mononuclear cells (MNCs), 2.0×10⁶ MM.1S cells and 2.0×10⁶ NCI-H929 cells were respectively subcutaneously inoculated into NOD.CB17-Prkdc^scid Il2rg^tm1/Bcgen (B-NDG) mice with a volume of 100 μl per mouse to establish mouse model. The morphologic, phenotypic, proliferative and genetic characteristics of PDX tumor were studied by hematoxylin-eosin staining, immunohistochemical staining (IHC), cell cycle analysis, flow cytometry and fluorescence in situ hybridization (FISH). The sensitivity of PDX tumor to bortezomib and anlotinib monotherapy or in combination was investigated through cell proliferation, apoptosis and in vitro and in vivo experiments. The effects of anlotinib therapy on tumor blood vessel and cell apoptosis were analyzed by IHC, TUNEL staining and confocal fluorescence microscope. RESULTS: MM PDX model was successfully established by subcutaneously inoculating primary MNCs. The morphologic features of tumor cells from MM PDX model were similar to those of mature plasma cells. MM PDX tumor cells positively expressed CD138 and CD38, which presented 1q21 amplification, deletion of Rb1 and IgH rearrangement, and had a lower proliferative activity than MM cell lines. in vitro, PDX, MM.1S and NCI-H929 cells were treated by bortezomib and anlotinib for 24 hours, respectively. Cell viability assay showed that the IC₅₀ value of bortezomib were 5 716.486, 1.025 and 2.775 nmol/L, and IC₅₀ value of anlotinib were 5 5107.337, 0.706 and 5.13 μmol/L, respectively. Anlotinib treatment increased the apoptosis of MM.1S cells (P < 0.01), but did not affect PDX tumor cells (P >0.05). in vivo, there was no significant difference in PDX tumor growth between bortezomib monotherapy group and control group (P >0.05), while both anlotinib monotherapy and anlotinib combined with bortezomib effectively inhibited PDX tumor growth (both P < 0.05). The vascular perfusion and vascular density of PDX tumor were decreased in anlotinib treatment group (both P < 0.01). The apoptotic cells in anlotinib treatment group were increased compared with those in control group (P < 0.05). CONCLUSION Bortezomib-resistant MM PDX model can be successfully established by subcutaneous inoculation of MNCs from MM patients in B-NDG mice. This PDX model, which retains the basic biological characteristics of MM cells, can be used to study the novel therapies.
Animals ; Bortezomib ; Humans ; Multiple Myeloma/pathology* ; Mice ; Apoptosis ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; Xenograft Model Antitumor Assays ; Mice, Inbred NOD ; Disease Models, Animal ; Cell Proliferation ; Transplantation, Heterologous

Dysregulated RNA splicing is a well-recognized characteristic of colorectal cancer (CRC); however, its intricacies remain obscure, partly due to challenges in profiling full-length transcript variants at the single-cell level. Here, we employ high-depth long-read scRNA-seq to define the full-length transcriptome of colorectal epithelial cells in 12 CRC patients, revealing extensive isoform diversities and splicing alterations. Cancer cells exhibited increased transcript complexity, with widespread 3'-UTR shortening and reduced intron retention. Distinct splicing regulation patterns were observed between intrinsic-consensus molecular subtypes (iCMS), with iCMS3 displaying even higher splicing factor activities and more pronounced 3'-UTR shortening. Furthermore, we revealed substantial shifts in isoform usage that result in alterations of protein sequences from the same gene with distinct carcinogenic effects during tumorigenesis of CRC. Allele-specific expression analysis revealed dominant mutant allele expression in key oncogenes and tumor suppressors. Moreover, mutated PPIG was linked to widespread splicing dysregulation, and functional validation experiments confirmed its critical role in modulating RNA splicing and tumor-associated processes. Our findings highlight the transcriptomic plasticity in CRC and suggest novel candidate targets for splicing-based therapeutic strategies.
Humans ; Colorectal Neoplasms/metabolism* ; RNA Isoforms/metabolism* ; Single-Cell Analysis ; RNA Splicing ; Gene Expression Regulation, Neoplastic ; RNA, Neoplasm/metabolism* ; Transcriptome

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

Background and purpose:Long non-coding RNA(lncRNA)LINC01410,with a length of 647 bp,participates in a variety of tumor biological processes.However,the role and mechanism of LINC01410 involved in esophageal squamous cell carcinoma(ESCC)remain unclear.This study aimed to explore the potential mechanism of LINC01410 promoting ESCC proliferation and invasion,to provide a potential prognostic indicator and therapeutic target for individuals with ESCC.Methods:Gene Expression Profiling Interactive Analysis 2(GEPIA2)databases were used to analyze the expression of LINC01410 and overall survival in esophageal squamous cell carcinoma data set in the Cancer Genome Atlas(TCGA).Gene Set Enrichment Analysis(GSEA)was performed to identify the underlying signaling pathways involved in the biological effects of LINC01410 in ESCC.A total of 62 pairs of ESCC tissues and paracancerous tissues from ESCC patients who underwent radical surgery in the Department of Thoracic Surgery at the First Affiliated Hospital of Xinxiang Medical College and the First People's Hospital of Pingdingshan City from January 2020 to December 2021 were collected.This project has been approved by the Hospital Ethics Committee(First Affiliated Hospital of Xinxiang Medical College,No.2018036;First People's Hospital of Pingdingshan City,No.2019-018).The expression of LINC01410 in ESCC tissues was detected by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).We transfected EC109 cells with LV-NC or LV-over/LINC01410 and EC9706 cells with shRNA-NC or shRNA-LINC01410.Stable transfected cells(EC109/NC,EC109/OE,EC9706/NC and EC9706/KD)were selected in primary cell culture medium containing puromycin.The expression of LINC01410 was detected by RTFQ-PCR.The impact of LINC01410 on ESCC cell proliferation was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and colony formation assays.The effect of LINC01410 on ESCC cell invasion was detected by transwell migration assay.T cell factor/lymphoid enhancer factor 1(TCF/LEF1)luciferase reporter assay was performed to validate the effect of LINC01410 on the activity of canonical Wnt/β-catenin signaling pathway.The expressions of Wnt/β-catenin and epithelial-mesenchymal transition(EMT)signal pathway related proteins in ESCC cells were detected by Western blot.Results:By analyzing the LINC01410 expression from ESCC samples in TCGA by GEPIA2,we found LINC01410 was consistently increased in ESCC tumors compared with normal tissues(P＜0.05),and high LINC01410 expression was associated with poorer overall survival(OS).RTFQ-PCR assay showed that expressions of LINC01410 were higher in esophageal cancer tissues and esophageal cancer cells(EC109 and EC9706)than in precancerous tissues and HEEC cells(P＜0.05).The expression level of LINC01410 was significantly correlated with invasion range,lymph node metastasis and TNM stage in ESCC patients(P＜0.01).LINC01410 expression was also upregulated in EC109/OE,however the expression of LINC01410 in EC9706/KD was decreased(P＜0.01).MTT assay showed overexpression of LINC01410 increased the viability of EC109 cells,while knockdown of LINC01410 decreased the viability of EC9706 cells(P＜0.01).Colony formation assay indicated that overexpression of LINC01410 enhanced the clonogenic ability of ESCC cells,while knockdown of LINC01410 reduced colony formation(P＜0.01).Transwell migration assay showed that LINC01410 overexpression drastically increased the number of migratory cells,while silencing of LINC01410 suppressed the migration in EC9706 cells(P＜0.01).GSEA revealed that Wnt/β-catenin and EMT pathways were significantly enriched in ESCC samples with a high level of LINC01410.TCF/LEF1 luciferase reporter assay showed higher levels of Wnt-dependent activities were observed in EC109/OE cells,whereas silenced LINC01410 in EC9706 cells led to contrary results(P＜0.01).Western blot analysis showed that overexpression of LINC01410 in EC109 cell significantly increased the expression levels of N-cadherin,β-catenin,cyclin D1,c-Myc and decreased E-cadherin expression,while knockdown LINC01410 resulted in opposite results.Conclusion:LINC01410 promotes proliferation and metastasis of ESCC,which might be caused by activation of Wnt/β-catenin and EMT signaling pathways.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

BACKGROUND:Sarcopenia refers to age-related progressive,systemic muscle mass reduction and/or muscle strength decline or muscle physiological function decline,which is related to the occurrence of a variety of adverse outcomes in older adults.Exercise is considered to be one of the main strategies for combating sarcopenia in older adults,but there is a lack of specific intervention methods of different exercise patterns to intervene in sarcopenia. OBJECTIVE:To elaborate the main influencing factors of sarcopenia and the research progress of different exercise methods to improve sarcopenia in older adults,providing reference and basis for combating sarcopenia in older adults. METHODS:Web of Science,PubMed,CNKI,VIP,WanFang databases were retrieved for relevant literature published from January 2000 to October 2023 using the keywords of"sarcopenia,sport,exercise intervention,resistant training,aerobic exercise,whole body vibration training,mixed training,physical performance,muscle strength,muscle mass"in Chinese and English,respectively.A total of 126 articles were included for review. RESULTS AND CONCLUSION:Resistance exercise is still the most effective way to prevent and treat senile sarcopenia,and the effect of high-intensity resistance exercise is more significant.However,in practical application,we should pay attention to the gradual increase of training load intensity.Aerobic exercise combined with resistance exercise is more effective to improve muscle mass and function in the elderly than a single exercise mode.It is suggested that older adults can carry out the transition of low-intensity aerobic exercise in the early stage and increase resistance exercise individually in the late stage.Whole body vibration training is a new treatment method for the prevention and treatment of senile sarcopenia,but particular attention should be paid to the effects of frequency,amplitude,and duration on patients during practical application.Multicomponent exercise combines different exercise modes,which can give full play to their respective advantages,so as to personalize exercise interventions.

Hepatocellular carcinoma is one of the most common malignant tumors worldwide, posing a great threat to human health and life. Despite the tremendous progress in understanding the origin and molecular characterization of hepatocellular carcinoma, there are still few therapeutic options that can significantly increase the survival rate and improve the quality of life of patients. Protein post-translational modifications (PTMs) are regulatory mechanisms for protein activity, localization, expression, and interactions with other cellular molecules that induce changes in protein properties and functions. More and more studies have demonstrated that PTMs and immunotherapy play an important role in the development of hepatocellular carcinoma, even in the immunosurveillance of hepatocellular carcinoma and the treatment and prognosis of hepatocellular carcinoma patients. Traditional types of PTMs include phosphorylation, glycosylation, methylation, and ubiquitination. Phosphorylation affects cancer development and progression by regulating tumor cell proliferation, invasion and metastasis, and inhibiting apoptosis. There are two main types of glycosylation: O-glycosylation andN-glycosylation. Abnormal glycosylation not only promotes the proliferation and metastasis of hepatocellular carcinoma cells, but also plays an important role in immune recognition and immune escape. Common methylation modifications include DNA methylation, RNA methylation and histone methylation. Among them, histone methylation, as an important epigenetic regulatory mechanism, is of great theoretical and practical significance for understanding the mechanism of hepatocellular carcinoma as well as carrying out the corresponding prevention and immunotherapy. Ubiquitination plays an important role in the localization, metabolism, function, regulation and degradation of proteins, and it is regulated at different levels by ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), ubiquitin-conjugating enzyme (E3), and a series of deubiquitinating enzymes (DUBs) and is closely related to hepatocellular carcinoma immunotherapy. This paper begins with a brief overview of the importance of PTMs of proteins, discusses the importance of these traditional types of PTMs in hepatocellular carcinoma immunotherapy, and summarizes the most recent applications of these approaches in hepatocellular carcinoma in order to explore the mechanism of action of PTMs in hepatocellular carcinoma immunotherapy. Then, we summarize the finding that programmed death-ligand 1 (PD-L1) is associated with a variety of conventional types of PTMs, that in-depth study of the mechanisms regulating PD-L1 expression in tumor cells is expected to improve therapeutic efficacy, and that targeting PD-L1 in PTMs is expected to be a new field for exploring hepatocellular carcinoma immunotherapy in the future. Finally, we discuss the current status of research on PTMs for hepatocellular carcinoma immunotherapy and provide new insights and future research directions. In addition to the traditional types of PTMs, multiple novel PTMs have also been identified in published research reports, while the relationship between novel PTMs and hepatocellular carcinoma and the types of PTMs to other undiscovered proteins are still poorly understood, and future research will be focused on a more comprehensive knowledge and understanding of PTMs as well as on exploring new types and mechanisms of PTMs. Overall, further investigation of the role of PTMs in tumor immunity could help to discover new biomarkers and to develop more effective and personalized cancer immunotherapies and targeted therapies, expanding our understanding of cancer biology.