ObjectiveGliomas in the motor functional area can damage the corticospinal tract (CST), leading to motor dysfunction. Currently, there is a lack of unified methods for evaluating the extent of CST damage, especially in patients with high surgical risk where the minimum distance from the lesion to the CST is less than 10 mm. This study aims to further clarify the classification method and clinical significance of CST morphological changes in these patients. MethodsThis retrospective study analyzed 109 high-risk functional area glioma patients who underwent neurosurgical treatment with preoperative diffusion tensor imaging (DTI) imaging and intraoperative neurostimulation guidance between 2014 and 2024. All patients had a lesion-to-tract distance (LTD) of less than 10 mm between the CST and the lesion. Preoperative DTI evaluation of CST involvement-induced morphological changes were reviewed. Patients were divided into 3 groups: 17 cases (15.6%) with symmetric CST morphology compared to the healthy side (CST symmetry), 48 cases (44.0%) with significant CST morphology changes compared to the healthy side (CST deformation), and 44 cases (40.4%) with CST overlap with the tumor (CST overlap). Then we classified patients according to preoperative assessment of tumor-induced morphological changes, and analyze postoperative motor function for each category. ResultsPostoperative pathology showed a significantly higher proportion of high-grade gliomas (HGG) in the CST overlap group compared to the other two groups (P=0.001). Logistic regression analysis showed that CST overlap was a predictor of HGG (P=0.000). The rate of total tumor resection in the CST deformation group and overlap group was lower than in the CST symmetric group (P=0.008). There was a total of 41 postoperative hemiplegic patients, with 4 cases (23.5%) in the CST symmetric group, 11 cases (22.9%) in the CST deformation group, and 26 cases (59.1%) in the CST overlap group. CST overlap with the tumor predicted postoperative hemiplegia (P=0.016). Two-way ANOVA analysis of the affected/healthy side and CST morphology groups showed significant main effects of CST grouping and healthy-affected side (P=0.017 and P=0.010), with no significant interaction (P=0.31). The fractional anisotropy (FA) value in the CST overlap group and the affected side was lower. A decrease in the FA value on the affected side predicted postoperative hemiplegia (sensitivity 69.2%, specificity 71.9%). ConclusionWe have established a method to predict postoperative hemiplegia in high-risk motor functional area glioma patients based on preoperative CST morphological changes. CST overlap leads to a decrease in CST FA values. This method can be used for precise patient management and aid in accurate preoperative surgical planning.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

BACKGROUND:Zinc-based alloy medical implant materials have excellent mechanical properties,complete degradability and good biocompatibility,and are mainly used in orthopedic implants,cardiovascular stents,bile duct stents,tracheal stents,nerve catheters,etc. OBJECTIVE:To review the research progress of biodegradable zinc-based alloys in bone defect repair and prospect the promising research direction and achievements of zinc-based materials. METHODS:After searching PubMed,Web of Science,WanFang Data,and CNKI databases from the establishment of the database to June 2023,various relevant articles on biodegradable zinc-based alloys for bone implant material research were collected.The basic characteristics of biodegradable zinc based alloys were summarized,and the role of zinc-based alloys in promoting bone tissue repair was sorted and summarized.The current research hotspots and shortcomings were discussed. RESULTS AND CONCLUSION:(1)Zinc-based alloys have good biocompatibility.Using zinc-based alloys as the matrix material,with the help of scaffold structure construction technology and coating optimization process,the bone conductivity of zinc-based alloys will be effectively improved,and their degradation products will have efficient bone induction to regulate the gene expression of osteoblasts and osteoclasts,thereby promoting the repair and reconstruction of bone defects.(2)However,in the research on optimizing zinc-based alloys,the coating process is relatively insufficient,and additive loading technology is still lacking.(3)Zinc-based alloys have excellent mechanical and biological properties.Through special processes,their bone conductivity and osteoinductivity can be increased to effectively improve their ability to promote bone repair and reconstruction,and it is expected to further achieve the development of personalized transplant materials.Further research and development are needed to optimize the integration of coating and additive loading technologies into zinc-based alloys.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective: To investigate the indoor fine particulate matter (PM 2.5 ) pollution and its influencing factors in children s bedrooms using solid fuel, so as to provide evidence for effective strategy to reduce PM 2.5 pollution. Methods: From December 2019 to November 2020, 198 households (108 in the north, 90 in the south) from two pilots in the north(Jiamusi in Heilongjiang Province) and south of China (Mianyang in Sichuan Province) were selected, and status of solid fuels using were obtained through home visits, dynamic changes in PM 2.5 concentrations in children s bedrooms were monitored by using real time online instruments, and the influencing factors of PM 2.5 pollution were analyzed by using a mixed effects model. Results: During the monitoring period, the daily PM 2.5 concentrations in the northern and southern pilot were 78.33 (40.50, 154.80) and 38.54(26.20, 58.46) μg/m 3, respectively, exceeding standard rates of 44.57% and 33.22%. During the heating period, the daily PM 2.5 concentrations in the northern and southern pilot were 212.50(133.60,244.10) and 104.42(73.97, 134.90) μg/m 3, respectively, with over standard rates of 96.75% and 86.96%. The mixed effects model analysis results showed that children s bedroom PM 2.5 concentrations were associated with solid fuel usage duration, window opening time, room layout (shared entrance door between kitchen and bedroom), indoor smoking, indoor humidity, and solid fuel use in the bedroom ( β =0.19, -0.05, 1.20, 0.43, 0.02, 0.35, all P <0.05). Conclusion Solid fuel combustion significantly comtributes to PM 2.5 pollution in children s bedrooms, with more pronounced impacts observed in northern China compared to southern regions.

Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Objective:To investigate the toxic effect of chlorambucil combined with ibrutinib on mantle cell lymphoma(MCL)cell line Jeko-1 and its related mechanism.Methods:The MCL cell line Jeko-1 was incubated with different concentrations of chlorambucil or ibrutinib or the combination of the two drugs,respectively.CCK-8 assay was used to detect the proliferation of the cells,and Western blot was used to measure the protein expression levels of BCL-2,caspase-3,PI3K,AKT and P-AKT.Results:After Jeko-1 cells were treated with chlorambucil(3.125,6.25,12.5,25,50 μmol/L)and ibrutinib(3.125,6.25,12.5,25,50 μmol/L)alone for 24,48,72h respectively,the cell proliferation was inhibited in a time-and dose-dependent manner.Moreover,the two drugs were applied in combination at low doses(single drug inhibition rate＜50％),and the results showed that the combination of two drugs had a more significant inhibitory effect(all P＜0.05).Compared with the control group,the apoptosis rate of the single drug group of chlorambucil(3.125,6.25,12.5,25,50 μmol/L)and ibutinib(3.125,6.25,12.5,25,50 μmol/L)was increased in a dose-dependent manner.The combination of the two drugs at low concentrations(3.125,6.25,12.5 μmol/L)could significantly increase the apoptosis rate compared with the corresponding concentration of single drug groups(all P＜0.05).Compared with control group,the protein expression levels of caspase-3 in Jeko-l cells were upregulated,while the protein expression levels of BCL-2,PI3K,and p-AKT/AKT were downregulated after treatment with chlorambucil or ibrutinib alone.The combination of the two drugs could produce a synergistic effect on the expressions of the above-mentioned proteins,and the differences between the combination group and the single drug groups were statistically significant(all P＜0.05).Conclusion:Chlorambucil and ibrutinib can promote the apoptosis of MCL cell line Jeko-1,and combined application of the two drugs shows a synergistic effect,the mechanism may be associated with the AKT-related signaling pathways.

Objective:To systematically evaluate the methodological quality and reporting quality of randomized controlled tri-als(RCT)on the treatment of BPH with traditional Chinese medicine(TCM),in order to provide some methodological reference for clinical practice and research.Methods:We searched CNKI,VIP,Wanfang Data and PubMed for RCTs on the treatment of BPH with TCM published in China from January 2013 to November 2023.Two researchers screened the literature separately,and evaluated the methodological and reporting quality of the RCTs based on the Cochrane bias risk assessment tool and CONSORT TCM compound.Results:Totally,88 RCTs were included in this study.In terms of methodological quality,according to the Cochrane bias risk assess-ment tool,27 biases in the process of randomization were identified as of low-risk and the other 61 of a certain risk.Among the alloca-tion-related biases deviating from the established interventions,76 were of low risk,10 of a certain risk and 2 of high risk;among the compliance-related biases deviating from the established interventions,76 were of low risk and 12 of a certain risk;among the biases due to missing outcome data,86 were of low risk and 2 of a certain risk,while all the biases due to outcome measurement were of low risk;and among the biases from selective reporting,65 were of low-risk,2 of a certain risk and 21 of high-risk.In terms of reporting quality,according to the evaluation criteria of consort TCM compound,appropriate key words were used in 1 RCT(0.01％),the ran-dom assignment sequence method described in 27(30.68％),the details of assignment limitation given in 5(5.68％),assignment concealment mentioned in 3(3.41％),the blind method and assignment concealment employed in 3(3.41％),fall-offs recorded in 10(11.36％),adverse events reported in 38(43.18％),and limitations of the trials analyzed in 18(20.45％).All the RCTs lacked complete intervention measures,subject flow chart,clinical trial registration and research schemes.Conclusion:At present,the methodological quality and reporting quality of RCTs on the treatment of BPH with TCM are generally low,with the main problems of incomplete experimental designs,lack of detailed description of randomized and blind methods,and insufficient TCM symptom eval-uation of outcome indicators.Researchers should be cautious in adopting and applying the results reported,follow the CONSORT state-ment in design,registration,implement and reporting of the scheme,fully consider the clinical characteristics of TCM in the treatment of BPH,and reasonably design and report the evaluation indicators.

Background and purpose:Epidermal growth factor receptor exon 20 T790M(EGFR T790M)mutation is one of the acquired resistance mechanisms in non-small cell lung cancer(NSCLC)against first-/second-generation EGFR tyrosine kinase inhibitors(EGFR TKIs).Additionally,EGFR T790M mutation can also be observed in NSCLC patients who have not undergone EGFR TKIs treatment.This study aimed to compare the clinical pathological characteristics and prognostic differences between NSCLC patients with de novo and acquired EGFR T790M mutation,and further explore the immune microenvironment features of acquired T790M mutation in NSCLC.Methods:This study retrospectively included 3 762 cases of NSCLC diagnosed at Fudan University Shanghai Cancer Center from April 2020 to September 2022.Among them,2 070 cases(55.02%)exhibited EGFR mutations,and 556 cases(14.77%)received EGFR TKIs treatment.Specifically,there were 119 cases(3.16%)of NSCLC with EGFR T790M mutation,including 51 cases(1.35%)of de novo T790M mutation and 68 cases(1.81%)of acquired EGFR T790M mutation.Clinical data of the patients were collected for comparative analysis between NSCLC patients with de novo and acquired T790M mutation.Multiple immunofluorescence histochemistry(mIHC)was employed to explore the immune microenvironment characteristics of NSCLC patients with acquired T790M mutation.Results:The proportion of de novo and acquired T790M mutations was higher in female patients compared to males.Patients with de novo T790M mutation tended to be younger.Both de novo and acquired T790M mutations were more commonly found in poorly differentiated carcinomas.Among NSCLC patients with de novo T790M mutation,there was a higher rate of programmed death ligand-1(PD-L1)expression(60.00%).In contrast,among NSCLC patients with acquired T790M mutation,the rate of PD-L1 expression was lower(22.39%).Acquired T790M mutation in NSCLC was often accompanied by TP53 alterations(39.7%).Cox regression analysis results indicated that mesenchymal to epithelial transition(MET)factor alteration was a risk factor for the occurrence of acquired T790M mutation(P=0.000 5).The average overall survival(OS)showed no significant difference between de novo and acquired T790M mutations(35.4 and 37.3 months respectively).However,patients with acquired T790M mutation exhibited a higher proportion of recurrence and metastasis.In acquired T790M mutation,there was a higher presence of immune cell infiltration within the stromal compartment,such as CD20+B cells,CD23+B cells,CD8+T cells,CD8+PD-1-/+cells,CD20+PD-1-/+cells and CD23+PD-1-/+cells.Additionally,the study found that when EGFR was accompanied by tumor suppressor gene(TSG)alterations,the average distance between tumor cells and CD8+T cells,CD20+B cells,CD8+PD-1+cells,CD20+PD-1+cells and CD23+PD-1+cells was closer compared to cases with only EGFR mutations.Conclusion:In comparison to patients with de novo T790M mutation,patients with acquired T790M mutation exhibit a lower rate of PD-L1 positivity.Acquired T790M mutation often accompanies TP53 alterations,and MET alteration is identified as a risk factor triggering acquired T790M mutation.Although patients with acquired T790M mutation face higher risk of recurrence and metastasis,their average OS does not significantly differ from those with de novo T790M mutation.In cases of acquired T790M mutation,the presence of TSG mutations can alter the spatial distribution of immune cells,potentially leading to benefits from immunotherapy.