Cirrhotic-extracellular matrix attenuates aPD-1 treatment response by initiating immunosuppressive neutrophil extracellular traps formation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is closely associatedwith chronic liver diseases, particularly liver cirrhosis, which has an altered extracellular matrix (ECM) composition. The influence and its mechanism of the cirrhotic-ECM on the response of HCC to immune checkpoint inhibitor (ICI) remains less clarified. METHODS: In silico, proteomic and pathological assessment of alteration of cirrhotic-ECM were applied in clinical cohort. Multiple pre-clinical models with ECM manipulation were used to evaluate cirrhotic-ECM's effect on ICI treatment. In silico, flow cytometry and IHC were applied to explore how cirrhotic-ECM affect HCC microenvironment. In vitro and in vivo experiments were carried out to identify the mechanism of how cirrhotic-ECM undermined ICI treatment. RESULTS: We defined "a pro-tumor cirrhotic-ECM" which was featured as the up-regulation of collagen type 1 (Col1). Cirrhotic-ECM/Col1 was closely related to impaired T cell function and limited anti PD-1 (aPD-1) response of HCC patients from the TCGA pan cancer cohort and the authors' institution, as well as in multiple pre-clinical models. Mechanically, cirrhotic-ECM/Col1 orchestrated an immunosuppressive microenvironment (TME) by triggering Col1-DDR1-NFκB-CXCL8 axis, which initiated neutrophil extracellular traps (NETs) formation to shield HCC cells from attacking T cells and impede approaching T cells. Nilotinib, an inhibitor of DDR1, reversed the neutrophils/NETs dominant TME and efficiently enhanced the response of HCC to aPD-1. CONCLUSIONS: Cirrhotic-ECM modulated a NETs enriched TME in HCC, produced an immune suppressive TME and weakened ICI efficiency. Col1 receptor DDR1 could be a potential target synergically used with ICI to overcome ECM mediated ICI resistance. These provide a mechanical insight and novel strategy to overcome the ICI resistance of HCC.

Use of Network Pharmacology and Experiment Validation to Uncover the Mechanism of Jianshen Lishui Prescription in the Treatment of Intracerebral Hemorrhage.

BACKGROUND: As a Chinese medicinal formula, the Jianshen Lishui prescription has been clinically proven to be effective in treating intracerebral hemorrhage (ICH). Yet, the mechanisms involved are unknown. METHODS: (1) Network pharmacology analysis: It involved the screening of active components in the Jianshen Lishui prescription, identification of potential targets for these components, and the screening of ICH-related targets. Common targets for both disease and drug were identified. Protein- protein interaction networks were constructed, followed by further screening of core targets. Gene Ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment analysis were performed on these core targets. Finally, molecular docking verification was carried out using the active components and core targets. (2) Experimental verification: It was conducted using a rat model of intracerebral hemorrhage. This involved observing neurological deficit scores in the rats and measuring cerebral water content. The effects of Jianshen Lishui prescription on the neurological function, cerebral water content, and brain tissue core targets were observed through HE staining, Western blot and qPCR. RESULTS: (1) In this study, 29 common targets were obtained by intersecting 256 potential drug targets and 642 genes associated with ICH. 9 core targets were obtained by employing the protein- protein interaction (PPI) construction system to screen more specific targets. In addition, the findings revealed that the molecular mechanism of Jianshen Lishui prescription in treating ICH was mainly related to cancer signaling pathways and signal transduction pathways, based on the results of GO and KEGG enrichment analysis. Molecular docking results showed that the active constituent of Jianshen Lishui prescription mannitol has the highest binding activity with KRAS, luteolin, and Poria sterol with AR, INS1 and KRAS, cerebrosterol with GNB1, INS and ESR1, and sitosterol with AR, INS1 and KRAS. (2) Animal experiments verified that Jianshen Lishui prescription significantly alleviated encephaledema and improved nerve functions of the rat model of ICH. And INS1 expression levels were upregulated and the expression levels of AR, KRAS, PTGS2, and ESR1 were down-regulated by the prescription. CONCLUSION: Jianshen Lishui prescription protects the nerve function of ICH patients by inhibiting inflammation and reducing cerebral edema. This study provides more supportive evidences for the clinical use of traditional Chinese prescriptions in ICH treatment.

Single-cell mapping reveals several immune subsets associated with liver metastasis of pancreatic ductal adenocarcinoma.

BACKGROUND: Identifying a metastasis-correlated immune cell composition within the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) will help to develop promising and innovative therapeutic strategies. However, the dynamics of immune cell lineages in the TME of advanced PDAC remains elusive. METHODS: Twenty-six samples from 11 patients (including 11 primary tumor tissues, 10 blood, and 5 lymph nodes) with different stages were used to develop a multiscale immune profile. High-dimensional single-cell analysis with mass cytometry was performed to search for metastasis-correlated immune changes in the microenvironment. The findings were further validated by published single-cell RNA sequencing (scRNA-seq) data and multiplex fluorescent immunohistochemistry. FINDINGS: High-dimensional single-cell profiling revealed that the three immune-relevant sites formed a distinct immune atlas. Interestingly, the PDAC microenvironment with the potential for metastatic spread to the liver was characterized by a decreased proportion of CD103+PD-1+CD39+ T cells with cytotoxic and exhausted functional status and an increased proportion of CD73+ macrophages. Analysis of scRNA-seq data of PDAC further confirmed the identified subsets and revealed strong potential interactions via various ligand-receptor pairs between the identified T subsets and the macrophages. Moreover, stratified patients with different immune compositions correlated with clinical outcomes of PDAC. CONCLUSIONS: Our study uncovered metastasis-correlated immune changes, suggesting that ecosystem-based patient classification in PDAC will facilitate the identification of candidates likely to benefit from immunotherapy. FUNDING: This work was supported by the National Key Research and Development Program of China, the Shanghai International Science and Technology Collaboration Program, the Shanghai Sailing Program, and the Key Laboratory of diagnosis and treatment of severe hepato-pancreatic diseases of Zhejiang Province.

Modulation of cellular metabolism by protein crotonylation regulates pancreatic cancer progression.

Protein lysine crotonylation has been recently identified as a vital posttranslational modification in cellular processes, particularly through the modification of histones. We show that lysine crotonylation is an important modification of the cytoplastic and mitochondria proteins. Enzymes in glycolysis, the tricarboxylic acid (TCA) cycle, fatty acid metabolism, glutamine metabolism, glutathione metabolism, the urea cycle, one-carbon metabolism, and mitochondrial fusion/fission dynamics are found to be extensively crotonylated in pancreatic cancer cells. This modulation is mainly controlled by a pair of crotonylation writers and erasers including CBP/p300, HDAC1, and HDAC3. The dynamic crotonylation of metabolic enzymes is involved in metabolism regulation, which is linked with tumor progression. Interestingly, the activation of MTHFD1 by decrotonylation at Lys354 and Lys553 promotes the development of pancreatic cancer by increasing resistance to ferroptosis. Our study suggests that crotonylation represents a metabolic regulatory mechanism in pancreatic cancer progression.

Status quo of hospice care service in community health service centers in Shanghai / 中华全科医师杂志

Objective:To survey the status quo of hospice care service in community health service centers in Shanghai.Methods:A questionnaire survey was conducted to investigate the situation of hospice care services from January 2021 to December 2021 in 16 community health service centers selected by stratified sampling from 16 districts in Shanghai.Results:Among 16 community health service centers, 13 provided inpatient hospice care services, 16 provide home hospice care and 14 provided outpatient hospice care services; and totally 1 935 (77.93%), 158 (6.36%) and 390 (15.71%) patients received palliative care, respectively. In centers providing inpatient hospice care service, the average bed number was 12 (10, 20); the annual number of patients was 58 (29, 137); the average length of hospital stay was (29.55±11.18) days; and the bed occupancy rate was (55.51±30.02)%, which in urban districts was significantly higher than that in rural districts ((74.76±19.33)% vs.(39.00±28.32)%; t=2.61, P=0.024). The number of patients receiving home hospice care in each center was 10 (3, 19) and the average duration of home service was (66.97±29.41) days. The proportion of physician fee of inpatient hospice care and that of home hospice care were (8.61±5.27)% and (6.25±3.11)%, respectively. While the proportion of medication expenses of inpatient hospice care and that of home hospice care were (35.60±16.13)% and(49.58±9.16)%, respectively. The outpatient hospice service were opened 2.0 (1.0, 4.0) days a week in 14 centers and 95 (58, 199) patients received services. Inpatient services were mainly provided for the patients with non-malignant chronic diseases (53.23%, 1 030/1 935), while home hospice care (89.87%, 142/158) and outpatient hospice care (83.85%, 327/390) mainly provided service for malignant patients. Conclusion:There is still room for improvement about the hospice care services delivered by community health service centers in Shanghai:discrepancy of utilization of hospice care services between urban districts and rural districts, low utilization of home and outpatient hospice care services, unreasonable cost composition in inpatient and home hospice care services.

Status quo and influencing factors of work stress among hospice care physicians and nurses / 中华全科医师杂志

Objective:To investigate the work stress and its influencing factors among hospice care physicians and nurses in medical institutions in Shanghai.Methods:It was a cross-sectional study. The study was carried out between December 2021 and January 2022. By use of multistage random sampling, 256 hospice care physicians and nurses were selected from community healthcare centers, secondary and tertiary hospitals in Shanghai to attend a WeChat-based survey using a self-designed questionnaire. The chi-square test was used to compare the differences in prevalence of work stress and stressors among all subjects with different characteristics. Binary logistic regression analysis was used to explore the major determinants associated with work stress. And the sources of work stress and the expepectd decompression countermeasures were investigated.Results:A total of 256 valid questionnaires were collected with a recovery rate of 100.0%. The median of work stress score was 7.5 (6.0, 9.0). Logistic regression analysis showed that those aged>40 years old and working for ≥5 years in hospice care service had higher level of work stress ( OR=3.78, 2.04; P=0.007, 0.039), and those with monthly income>10 000 RMB Yuan had lower level of work stress ( OR=0.34, P=0.005). The top three stressors were the death of patients (88.3%, 226/256), low income (78.1%, 200/256), difficulty in promotion (67.2%, 172/256). The top three way that doctors and nurses desired to reduce work stress were to increase income (88.3%, 226/256) and optimize performance appraisal target (78.1%, 200/256) and promotion mechanism (66.0%, 169/256). Conclusions:In general, the work stress among hospice care physicians and nurses is at a high level in Shanghai and the stressors are widely distributed. Age, monthly salary and years of working in hospice care unit are independent factors of work stress. Improving salary, optimizing performance appraisal target and promotion mechanism are the most desired strategies to reduce work stress among hospice care physicians and nurses.

Muscle architecture and intramuscular nerve distribution pattern of adult elbow muscle / 解剖学报

[Abstract] Objective To study the morphology, muscle architecture index and distribution pattern of intramuscular nerve dense area of elbow muscle, so as to provide anatomical location for poster-lateral approach of elbow joint and transplantation of elbow muscle flap. Methods Through gross anatomy, muscle architecture index and modified Sihler’s intramuscular nerve staining, 10 cases with an average age of 64. 2 years were selected. Results The elbow muscle was approximate triangle, the muscle wet weight was (6. 31±0. 85) g, the muscle length was (6. 24±0. 78) cm, the muscle fiber length was (4. 74±0. 88) cm, pennation angle(70. 60±6. 41)°and the muscle physiological cross-sectional area was (0. 41±0. 15) cm

Human Platelet-Rich Plasma-Derived Exosomes Promote the Proliferation of Schwann Cells Cultured in Vitro / 中国医学科学院学报

Objective To investigate the effect of human platelet-rich plasma-derived exosomes(PRP-exos)on the proliferation of Schwann cell(SC)cultured in vitro. Methods PRP-exos were extracted by polymerization-precipitation combined with ultracentrifugation.The morphology of PRP-exos was observed by transmission electron microscopy,and the concentration and particle size distribution of PRP-exos were determined by nanoparticle tracking analysis.Western blotting was employed to determine the expression of the marker proteins CD63,CD81,and CD9 on exosome surface and the platelet membrane glycoprotein CD41.The SCs of rats were isolated and cultured,and the expression of the SC marker S100β was detected by immunofluorescence staining.The fluorescently labeled PRP-exos were co-cultured with SCs in vitro for observation of their interaction.EdU assay was employed to detect the effect of PRP-exos on SC proliferation,and CCK-8 assay to detect the effects of PRP-exos at different concentrations(0,10,20,40,80,and 160 μg/ml)on SC proliferation. Results The extracted PRP-exos appeared as uniform saucer-shaped vesicles with the average particle size of(122.8±38.7)nm and the concentration of 3.5×1012 particles/ml.CD63,CD81,CD9,and CD41 were highly expressed on PRP-exos surface(P<0.001,P=0.025,P=0.004,and P=0.032).The isolated SCs expressed S100β,and PRP-exos could be taken up by SCs.PRP-exos of 40,80,and 160 μg/ml promoted the proliferation of SCs,and that of 40 μg/ml showed the best performance(all P<0.01). Conclusions High concentrations of PRP-exos can be extracted from PRP.PRP-exos can be taken up by SCs and promote the proliferation of SCs cultured in vitro.

Characteristics of the cancer stem cell niche and therapeutic strategies.

Distinct regions harboring cancer stem cells (CSCs) have been identified within the microenvironment of various tumors, and as in the case of their healthy counterparts, these anatomical regions are termed "niche." Thus far, a large volume of studies have shown that CSC niches take part in the maintenance, regulation of renewal, differentiation and plasticity of CSCs. In this review, we summarize and discuss the latest findings regarding CSC niche morphology, physical terrain, main signaling pathways and interactions within them. The cellular and molecular components of CSCs also involve genetic and epigenetic modulations that mediate and support their maintenance, ultimately leading to cancer progression. It suggests that the crosstalk between CSCs and their niche plays an important role regarding therapy resistance and recurrence. In addition, we updated diverse therapeutic strategies in different cancers in basic research and clinical trials in this review. Understanding the complex heterogeneity of CSC niches is a necessary pre-requisite for designing superior therapeutic strategies to target CSC-specific factors and/or components of the CSC niche.

The combination of PD-1 blockade with interferon-α has a synergistic effect on hepatocellular carcinoma.

BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs), such as programmed cell death protein-1 (PD-1) or its ligand 1 (PD-L1) antibody, in hepatocellular carcinoma (HCC) is limited, and it is recommended that they be combined with other therapies. We evaluated the combination of pegylated interferon-α (Peg-IFNα) with PD-1 blockade in HCC mouse models. METHODS: We analyzed the effects of Peg-IFNα on tumor-infiltrating immune cells and PD-1 expression in the HCC immune microenvironment and examined the underlying mechanism of its unique effect on the PD-1 pathway. The in vivo efficacy of anti-PD-1 and Peg-IFNα was evaluated in both subcutaneous and orthotopic mouse models of HCC. RESULTS: The combination of Peg-IFNα with PD-1 blockade dramatically enhanced T-cell infiltration, improved the efficacy of PD-1 antibody and prolonged mouse survival compared with PD-1 antibody monotherapy. Mechanistically, Peg-IFNα could recruit cytotoxic CD8+ T cells to infiltrate the HCC microenvironment by inducing tumor cells to secrete the chemokine CCL4. Nevertheless, the HCC microenvironment quickly overcame the immune responses by upregulating PD-1 expression in CD8+ T cells via the IFNα-IFNAR1-JAK1-STAT3 signaling pathway. The combination of PD-1 blockade with Peg-IFNα could restore the cytotoxic capacity of CD8+ T cells and exerted a significant synergistic effect on HCC. CONCLUSION: These results indicate that in addition to initiating the antitumor immune response itself, Peg-IFNα can also generate a microenvironment favoring PD-1 blockade. Thus, the combination of Peg-IFNα and PD-1 blockade can be a promising strategy for HCC.

Cholesterol suppresses GOLM1-dependent selective autophagy of RTKs in hepatocellular carcinoma.

Aberrant activation of receptor tyrosine kinases (RTKs) and the subsequent metabolic reprogramming play critical roles in cancer progression. Our previous study has shown that Golgi membrane protein 1 (GOLM1) promotes hepatocellular carcinoma (HCC) metastasis by enhancing the recycling of RTKs. However, how this RTK recycling process is regulated and coupled with RTK degradation remains poorly defined. Here, we demonstrate that cholesterol suppresses the autophagic degradation of RTKs in a GOLM1-dependent manner. Further mechanistic studies reveal that GOLM1 mediates the selective autophagy of RTKs by interacting with LC3 through an LC3-interacting region (LIR), which is regulated by a cholesterol-mTORC1 axis. Lowering cholesterol by statins improves the efficacy of multiple tyrosine kinase inhibitors (TKIs) in vivo. Our findings indicate that cholesterol serves as a signal to switch GOLM1-RTK degradation to GOLM1-RTK recycling and suggest that lowering cholesterol by statin may be a promising combination strategy to improve the TKI efficiency in HCC.

Driver mutations of intrahepatic cholangiocarcinoma shape clinically relevant genomic clusters with distinct molecular features and therapeutic vulnerabilities.

Purpose: To establish a clinically applicable genomic clustering system, we investigated the interactive landscape of driver mutations in intrahepatic cholangiocarcinoma (ICC). Methods: The genomic data of 1481 ICCs from diverse populations was analyzed to investigate the pair-wise co-occurrences or mutual exclusivities among recurrent driver mutations. Clinicopathological features and outcomes were compared among different clusters. Gene expression and DNA methylation profiling datasets were analyzed to investigate the molecular distinctions among mutational clusters. ICC cell lines with different gene mutation backgrounds were used to evaluate the cluster specific biological behaviors and drug sensitivities. Results: Statistically significant mutation-pairs were identified across 21 combinations of genes. Seven most recurrent driver mutations (TP53, KRAS, SMAD4, IDH1/2, FGFR2-fus and BAP1) showed pair-wise co-occurrences or mutual exclusivities and could aggregate into three genetic clusters: Cluster1: represented by tripartite interaction of KRAS, TP53 and SMAD4 mutations, exhibited large bile duct histological phenotype with high CA19-9 level and dismal prognosis; Cluster2: co-association of IDH/BAP1 or FGFR2-fus/BAP1 mutation, was characterized by small bile duct phenotype, low CA19-9 level and optimal prognosis; Cluster3: mutation-free ICC cases with intermediate clinicopathological features. These clusters showed distinct molecular traits, biological behaviors and responses to therapeutic drugs. Finally, we identified S100P and KRT17 as "cluster-specific", "lineage-dictating" and "prognosis-related" biomarkers, which in combination with CA19-9 could well stratify Cluster3 ICCs into two biologically and clinically distinct subtypes. Conclusions: This clinically applicable clustering system can be instructive to ICC prognostic stratification, molecular classification, and therapeutic optimization.

Pain management for cancer patients in hospice wards of community health centers / 中华全科医师杂志

Objective:To investigate the status quo of pain management for cancer patients in hospice care wards of community health service centers.Methods:The electronic medical records of 373 cancer patients admitted in hospice wards of Kangjian Community Health Center of Xuhui District and Jinshanwei Town Community Health Center of Jinshan District from January 2015 to July 2021 were collected. The characteristics of cancer pain, the use of analgesic drugs, the effects of analgesic drugs and its influencing factors were analyzed.Results:The incidence of cancer pain in 373 patients was 93.0% (347/373), and the proportion of moderate to severe cancer pain was 55.6% (193/347). Analgesics were used in 304 patients, among whom 233 (76.6%) patients used oral analgesics, 297 (97.7%) used on time, 97.6%(285/292) used sustained-release opioids, and 94 (30.9%) used combinedly. Breakout pain occurred in 100 cases (32.9%), all of which was controlled with immediate-release morphine. Cancer pain was not relieved in 132 cases (43.42%), and multivariate logistic regression analysis showed that the pain degree on admission (moderate: OR=3.69, 95 %CI:2.09-6.49; severe: OR=5.52, 95 %CI:2.43-12.53), the presence of burst pain ( OR=3.28, 95 %CI:1.77-6.06), the type of analgesics used (non-steroidal+weak opioids: OR=0.39, 95 %CI:0.20-0.76; nonsteroidal+strong opioids: OR=0.20, 95 %CI:0.08-0.51) and the adverse reactions ( OR=1.92, 95 %CI:1.03-3.60) were the influencing factors of pain relief in cancer pain patients (all P<0.05). Conclusion:The pain of cancer patients admitted to community palliative care wards cannot be ignored. Although most cancer pain patients use analgesic drugs in a standard way, there are still a high proportion of patients whose pain is not controlled. Various factors affect the effect of analgesic treatment.

The molecular biology of pancreatic adenocarcinoma: translational challenges and clinical perspectives.

Pancreatic cancer is an increasingly common cause of cancer mortality with a tight correspondence between disease mortality and incidence. Furthermore, it is usually diagnosed at an advanced stage with a very dismal prognosis. Due to the high heterogeneity, metabolic reprogramming, and dense stromal environment associated with pancreatic cancer, patients benefit little from current conventional therapy. Recent insight into the biology and genetics of pancreatic cancer has supported its molecular classification, thus expanding clinical therapeutic options. In this review, we summarize how the biological features of pancreatic cancer and its metabolic reprogramming as well as the tumor microenvironment regulate its development and progression. We further discuss potential biomarkers for pancreatic cancer diagnosis, prediction, and surveillance based on novel liquid biopsies. We also outline recent advances in defining pancreatic cancer subtypes and subtype-specific therapeutic responses and current preclinical therapeutic models. Finally, we discuss prospects and challenges in the clinical development of pancreatic cancer therapeutics.

Organ-specific cholesterol metabolic aberration fuels liver metastasis of colorectal cancer.

Rationale: Metastasis, the development of secondary malignant growth at a distance from a primary tumor, is the main cause of cancer-associated death. However, little is known about how metastatic cancer cells adapt to and colonize in the new organ environment. Here we sought to investigate the functional mechanism of cholesterol metabolic aberration in colorectal carcinoma (CRC) liver metastasis. Methods: The expression of cholesterol metabolism-related genes in primary colorectal tumors (PT) and paired liver metastases (LM) were examined by RT-PCR. The role of SREBP2-dependent cholesterol biosynthesis pathway in cell growth and CRC liver metastasis were determined by SREBP2 silencing in CRC cell lines and experimental metastasis models including, intra-splenic injection models and liver orthotropic injection model. Growth factors treatment and co-culture experiment were performed to reveal the mechanism underlying the up-regulation of SREBP2 in CRC liver metastases. The in vivo efficacy of inhibition of cholesterol biosynthesis pathway by betulin or simvastatin were evaluated in experimental metastasis models. Results: In the present study, we identify a colorectal cancer (CRC) liver metastasis-specific cholesterol metabolic pathway involving the activation of SREBP2-dependent cholesterol biosynthesis, which is required for the colonization and growth of metastatic CRC cells in the liver. Inhibiting this cholesterol biosynthesis pathway suppresses CRC liver metastasis. Mechanically, hepatocyte growth factor (HGF) from liver environment activates SREBP2-dependent cholesterol biosynthesis pathway by activating c-Met/PI3K/AKT/mTOR axis in CRC cells. Conclusion: Our findings support the notion that CRC liver metastases show a specific cholesterol metabolic aberration. Targeting this cholesterol biosynthesis pathway could be a promising treatment for CRC liver metastasis.

IFN-α facilitates the effect of sorafenib via shifting the M2-like polarization of TAM in hepatocellular carcinoma.

Tumor-associated macrophages (TAMs) and how they are activated play critical roles in tumor progression and metastasis, and in hepatocellular carcinoma (HCC), they are associated with sorafenib resistance. Reprogramming of TAMs into M1-like macrophages has been proposed as an approach to stimulate tumor regression. Here we studied the collective effects of interferon-alpha (IFN-α) and sorafenib on HCC. We found that IFN-α delayed tumor growth and inhibited pulmonary metastasis in an orthotopic HCC implantation model. Via in vitro studies, we found that IFN-α treatment could reprogram M2-like RAW264.7 and THP-1 macrophage cells toward M1-like cells. In addition, we also found that IFN-α combined with a low dose of sorafenib has a synergistic inhibitory effect on HCC tumor growth and pulmonary metastasis without obvious toxicity in an in vivo mice model. Moreover, IFN-α increased sorafenib's therapeutic efficacy by shifting TAM polarization to an M1-like phenotype, increasing and activating intratumoral CD8+ T cells in HCCs. In conclusion, a combination of IFN-α and sorafenib have synergistic inhibitory effects on HCC growth and metastasis resulting from a shift in TAM polarization rather than their depletion. Our study supports the future clinical use of a combination of IFN-α and sorafenib for the treatment of advanced HCC.

Clinical study of IOL Master in patients with silicone oil eye complicated with cataract / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To explore the postoperative refractive error and influence factors using the Optical Biometry(IOL Master)in patients with silicone oil filled eye complicated cataract after silicone oil removal combined with cataract surgery.<p>METHODS: From August 2020 to November 2020 in the Affiliated Eye Hospital of Nanchang University, 41 patients with silicone oil removal combined with cataract surgery were divided into 2 groups: 18 patients(18 eyes)in high myopia group and 23 patients(23 eyes)in non-high myopia group. Collected and recorded the patients' IOL Master measurement data. Statistical analysis was performed in SPSS20.0.<p>RESULTS: The mean spherical degree or astigmatism of the IOL Master measurement and refraction in high myopia and non-high myopia group performed by paired <i>t</i>-test(<i>P</i>>0.05). The mean axial difference ΔAL were -0.28±0.29 and 0.05±0.31mm between the two groups has no difference(<i>P</i><0.05), while ΔK, mean absolute refractive error(MARE)and Δastigmatism(<i>P</i>>0.05). The preoperative and postoperative axial length(AL)in high myopia groups were 28.37±1.73 and 28.10±1.55mm(<i>t</i>=3.994, <i>P</i><0.05), yet the non-high myopia group(<i>P</i>>0.05). Bivariate linear correlation analysis: in the high myopia group, there was a moderate positive correlation between preoperative AL and MARE(<i>r</i>=0.742, <i>P</i><0.05), and a moderate negative correlation between ΔAL and MARE(<i>r</i>=-0.646, <i>P</i><0.05), but in non-high myopia group, preoperative AL, ΔAL, preoperative K, ΔK had no correlation(<i>P</i>>0.05).<p>CONCLUSION: IOL Master performed the small biostatistical error and high measurement accuracy of the intraocular lens in patients with silicone oil filled eye complicated cataract. The longer preoperative AL, the more changes in the axial length after silicone oil removal, and the greater the refractive error of patients with high myopia silicone oil filled eye complicated cataract.

Clinical observation of the axial length and corneal curvature after silicone oil removal combined with cataract surgery in high myopia patients / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To explore the postoperative axial length(AL)and corneal curvature(K)shift in high myopia silicone oil patients complicated cataract after silicone oil removal combined with cataract surgery as well as the relationship.<p>METHODS: From August 2020 to November 2020 in the Affiliated Eye Hospital of Nanchang University, 45 patients(48 eyes)with silicone oil eye complicated cataract were divided into 2 groups: 20 eyes of 20 patients(refraction ≥-6.00D and AL ≥26mm)in high myopia group and 28 eyes of 25 patients(refraction < -6.00D or AL <26mm)in non-high myopia group. Record the general information and IOL-Master measurement data AL and K, statistical analysis was performed. <p>RESULTS: There was no difference in preoperative and postoperative K value of two groups(all <i>P</i>>0.05). The AL of the patients in the high myopia group was 28.35±1.68mm after silicone oil removal combined with cataract surgery, which was shorter than 28.08±1.53mm before the operation(<i>P</i><0.001), yet not statistically significant in non-high myopia group(<i>P</i>>0.05). The median ΔAL of patients in the high myopia group was \〖-0.28(-0.44, -0.08)\〗 compared with the non-high myopia group \〖-0.06(-0.20, 0.15)\〗, which was statistically different(<i>P</i><0.05), but no significant difference in both ΔK(<i>P</i>>0.05). There was no correlation between |ΔAL| and |ΔK|, or and preoperative K values(<i>P</i>>0.05)in two groups. Preoperative AL was moderately positive correlated with |ΔAL| in the high myopia group(<i>r</i>=0.702, <i>P</i>=0.01), but not in the non-high myopia group(<i>P</i>>0.05).<p>CONCLUSION: There was no significant shift in K value of high myopia group with silicone oil eye complicated cataract after the silicone oil removal combined with cataract surgery. The longer preoperative AL in high myopia group, the more likely become shorter after surgery, meanwhile the longer AL, the greater AL shift.

Advance in metabolism and target therapy in breast cancer stem cells.

Breast cancer, like many other cancers, is believed to be driven by a population of cells that display stem cell properties. Recent studies suggest that cancer stem cells (CSCs) are essential for tumor progression, and tumor relapse is thought to be caused by the presence of these cells. CSC-targeted therapies have also been proposed to overcome therapeutic resistance in breast cancer after the traditional therapies. Additionally, the metabolic properties of cancer cells differ markedly from those of normal cells. The efficacy of metabolic targeted therapy has been shown to enhance anti-cancer treatment or overcome therapeutic resistance of breast cancer cells. Metabolic targeting of breast CSCs (BCSCs) may be a very effective strategy for anti-cancer treatment of breast cancer cells. Thus, in this review, we focus on discussing the studies involving metabolism and targeted therapy in BCSCs.

PKM2 Drives Hepatocellular Carcinoma Progression by Inducing Immunosuppressive Microenvironment.

Background and Aims: Pyruvate kinase M2 (PKM2) is an essential regulator of the Warburg effect, but its biological function promoting immune escape of hepatocellular carcinoma (HCC) is unclear. Methods: GEPIA web tool and immunohistochemistry (IHC) analysis were employed to evaluate the clinical relevance of PKM2 in HCC patients. Both in vitro CCK-8, colony formation, and transwell assays, and in vivo xenografts were performed to evaluate the malignancy of HCC cells. PKM2 and PD-L1 levels were examined by Western blot, qRT-PCR, and IHC. The role of PKM2 on in vivo immune response was also investigated. Results: PKM2 was significantly upregulated in HCC and associated with a poor prognosis of HCC patients. Knockdown of PKM2 inhibited in vitro proliferation, migration, and invasion of HCC cells, as well as in vivo tumor growth. Strikingly, PKM2 showed a strong correlation with the expression of immune inhibitory cytokines and lymphocyte infiltration in HCC. The overexpression of PKM2 sensitized HCC to immune checkpoint blockade, which enhanced IFN-γ positive CD8 T cells in HCC mice models. Conclusion: PKM2 might be a predictor and a potential therapeutic target for immune checkpoint inhibitors in HCC.