The most common subtype of lung cancer is non-small cell lung cancer (NSCLC), which has a poor prognosis and seriously threatens the health of human beings. The multidisciplinary comprehensive treatment model has gradually become the mainstream of NSCLC treatment. Traditional Chinese medicine (TCM) can be used effectively either as an adjunctive therapy or alone throughout the NSCLC therapy, which has a significant impact on survival, quality of life, and reduction of toxicity. Therefore, this paper reviewed the theoretical basis, the latest clinical application, and combined treatment mechanisms in order to explore the advantage stage of TCM treatment and the synergistic therapeutic mechanisms.

Objective:To analyze the plasma levels of soluble immune checkpoint molecules in patients with primary liver cancer and their prognostic significance.Methods:The levels of sCD28, sCD80, sCD137, sCD27, sGITR, sTIM3, sCTLA4, sHVEM, IDO, sLAG3, sBTLA, sPD1, sPDL1 and sPDL2 in plasma samples of 58 patients with primary liver cancer and 30 healthy controls were detected by liquid chip technology and compared between different groups. The relationship between the plasma levels of soluble immune checkpoint molecules and tumor recurrence was analyzed.Results:The levels of sCD28 and sCD80 were higher in patients in Barcelona Clinic Liver Cancer (BCLC) stage 0/A and B than in healthy controls and patients in BCLC-C stage ( P<0.05). However, the levels of sCD27 and sHVEM in BCLC-C patients were significantly lower than those in BCLC-0/A and BCLC-B patients, and even lower than healthy control group. The levels of sCD137, IDO and sPD1 in BCLC-0/A and BCLC-B patients were higher than those in healthy controls. The levels of sPDL1 and sPDL2 in different BCLC stages were all higher than those in healthy controls, and maintained at high level in the three stages, but there was no significant difference between different stages. After 24 months of interventional treatment, the preoperative sCD28 level was lower in patients with recurrent tumor recurrence than in patients without recurrence ( t=2.843, P=0.007). The optimal cut-off value of sCD28 based on the receiver operating characteristic (ROC) curve for predicting tumor recurrence was 101.42 pg/ml and the area under the ROC curve was 0.771 (95%CI: 0.611-0.931) with a sensitivity of 0.889 and a specificity of 0.666. The cumulative recurrence rate in patients with high sCD28 level (≥101.41 pg/ml) was 57.9% at 24 months after surgery, which was lower than the rate (95.5%) in patients with low sCD28 level (<101.41 pg/ml). The difference in the cumulative recurrence rate between the two groups was statistically significant (χ 2=15.777, P=0.000). Conclusions:The expression patterns of soluble immune checkpoint molecules varied in patients at different stages of primary liver cancer, suggesting that there were differences in their immune status and sCD28 could be used as a prognostic marker for postoperative recurrence of liver cancer.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, with the features of insidious onset, low surgical resection rate, and frequent early metastasis and recurrence. With the development of new molecular biology technology in recent years, a liquid biopsy technology, circulating tumor DNA (ctDNA) detection, has achieved encouraging results. This article reviews the current research status and future prospects of ctDNA as a key component of liquid biopsy in patients with HCC, in order to provide new ideas for the clinical treatment of HCC.

Objective:To observe the therapeutic efficacy and prognosis of daratumumab combined with chemotherapy bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT) followed by daratumumab and lenalidomide maintenance treatment for primary plasma cell leukemia (PCL).Methods:The clinical data of a patient with primary PCL admitted to the First People's Hospital of Yunnan Province in January 2020 were retrospectively analyzed, and relevant literatures were reviewed.Results:The patient was diagnosed with primary PCL and treated with daratumumab combined with BD (bortezomib + dexamethasone) for 1 course and BCDD (bortezomib + cyclophosphamide + liposomaldoxorubicin + dexamethasone) for two courses. The patient was treated with daratumumab combined with allo-HSCT after complete remission. The donor cells were successfully implanted and the chimerism rate of donor cells was 94.36% without acute graft-versus-host disease reaction. And then the patient received intermittent maintenance therapy of daratumumab combined with low dose lenalidomide after transplantation, and the current remission period after transplantation reached 4 months.Conclusions:Daratumumab combined with chemotherapy bridging to allo-HSCT followed by daratumumab and lenalidomide may improve the prognosis of primary PCL and prolong survival time.

In the original publication Fig. 1D and supplementary material is incorrect. The correct figure and supplementary material is provided in this correction.

One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem (ES) cells, which is used to produce gene-targeted mice for wide applications in biomedicine. However, a major bottleneck in this approach is that the robustness of germline transmission of gene-targeted ES cells can be significantly reduced by their genetic and epigenetic instability after long-term culturing, which impairs the efficiency and robustness of mouse model generation. Recently, we have established a new type of pluripotent cells termed extended pluripotent stem (EPS) cells, which have superior developmental potency and robust germline competence compared to conventional mouse ES cells. In this study, we demonstrate that mouse EPS cells well maintain developmental potency and genetic stability after long-term passage. Based on gene targeting in mouse EPS cells, we established a new approach to directly and rapidly generate gene-targeted mouse models through tetraploid complementation, which could be accomplished in approximately 2 months. Importantly, using this approach, we successfully constructed mouse models in which the human interleukin 3 (IL3) or interleukin 6 (IL6) gene was knocked into its corresponding locus in the mouse genome. Our study demonstrates the feasibility of using mouse EPS cells to rapidly generate mouse models by gene targeting, which have great application potential in biomedical research.

Recently we have established a new culture condition enabling the derivation of extended pluripotent stem (EPS) cells, which, compared to conventional pluripotent stem cells, possess superior developmental potential and germline competence. However, it remains unclear whether this condition permits derivation of EPS cells from mouse strains that are refractory or non-permissive to pluripotent cell establishment. Here, we show that EPS cells can be robustly generated from non-permissive NOD-scid Il2rg mice through de novo derivation from blastocysts. Furthermore, these cells can also be efficiently generated by chemical reprogramming from embryonic NOD-scid Il2rg fibroblasts. NOD-scid Il2rg EPS cells can be expanded for more than 20 passages with genomic stability and can be genetically modified through gene targeting. Notably, these cells contribute to both embryonic and extraembryonic lineages in vivo. More importantly, they can produce chimeras and integrate into the E13.5 genital ridge. Our study demonstrates the feasibility of generating EPS cells from refractory mouse strains, which could potentially be a general strategy for deriving mouse pluripotent cells. The generation of NOD-scid Il2rg EPS cell lines permits sophisticated genetic modification in NOD-scid Il2rg mice, which may greatly advance the optimization of humanized mouse models for biomedical applications.

OBJECTIVETo investigate the differences in the expression profiles of circular RNA (circRNA) between luminal breast cancer cells and normal breast cells.

METHODSTotal RNA extracted from luminal breast cancer cells MCF7 and normal breast cells MCF10A was digested with Rnase R to remove linear RNAs and enrich circRNAs. The enriched circRNAs were amplified and transcribed into fluorescent cRNAs using a random priming method, and were hybridized onto the circRNA hybridization array. The circRNA expression profiles of MCF7 and MCF10A cells were analyzed using Agilent Feature Extraction software. Quantile normalization and subsequent data processing were performed, and volcano plot filtering and hierarchical clustering were utilized to analyze the circRNA expression patterns. The expressions of 3 circRNAs with significant log fold changes were validated using qPCR.

RESULTSThe hybridization array data revealed significant differences in the circRNA expression profiles between MCF7 and MCF10A cells. Compared with those of MCF10A cells, the 12910 circRNAs expressed in MCF7 cells showed 5964 up-regulated, 81 consistently regulated, and 6865 down-regulated circRNAs; 343 circRNAs showed a log fold change by more than 2 folds, among which 213 circRNAs were up-regulated and 130 were down-regulated. Nine circRNAs showed differential expressions by more than 2 folds, including 8 up-regulated ones, namely hsa_circRNA_061260 (6.02 folds), hsa_circRNA_103933 (5.96 folds), hsa_circRNA_005239 (5.84 folds), hsa_circRNA_100689 (5.69 folds), hsa_circRNA_004087 (5.60 folds), hsa_circRNA_104420 (5.25 folds), hsa_circRNA_104421 (5.13 folds) and hsa_circRNA_101222 (5.03 folds); only one circRNA was down-regulated, namely hsa_circRNA_104864 (5.09 folds). The expressions of hsa_circRNA_100689, hsa_circRNA_005239 and hsa_circRNA_104864 were further validated by qPCR, which yielded consistent results with the microarray data.

CONCLUSIONSThe circRNA expression profiles differ significantly between luminal breast cancer cells and normal breast cells. These differentially expressed circRNAs may serve as potential novel targets for the diagnosis of luminal breast cancer.

Objective:To observe the effects of Yikunjing capsules on the bone histomorphometry indexes and the serum Interleukin-6 (IL-6) level in mice with osteoporosis.Methods:60 cases ofC57 female mice were randomly divided into 5 groups,such as model group (equal volume of normal saline),estrogen group (nilestriol,0.25 mg/kg),Yikunjing capsules high dose group (1.44 g/kg),Yikunjing capsules medium dose group (0.72 g/kg) and Yikunjing capsules low dose group (0.36 g/kg),sham group (equal volume of normal saline) were treated with sham operation.The mice in each group was intragastrically administrated for 70 days.Enzyme linked immunosorbent assay (ELISA) was used to detect the serum IL-6 level.The bone histomorphometry index were detected with BI-2000 Medical Image Analysis System.And the Number of blood vessels in distal femoral metaphysis of each group was measured by CT.Results:Compared with the sham group,the width and area of trabecular bone,the thickness of cortical bone,area of trabecular bone,the number of osteoblasts,the bone mineral density and the number of blood vessels in model group were significantly reduced(P＜0.05),while the number of osteoclasts and serum IL-6 level were significantly increased (P＜0.05).Compared with the model group,above indexes in estrogen group,Yikunjing capsules high,medium,low dose group were improved (P＜0.05),and the effect of Yikunjing capsules high dose group and estrogen group was almost the same (P＞0.05).Conclusion:Yikunjing capsules can rectify the bone histomorphometry indexes reduce the serum IL-6 level and increase the number of blood vessels in mice with osteoporosis,and intragastrically administrating 1.44 g/kg Yikunjing capsules could get the better effect.

Objective To investigate the value of low-dose coronary artery imaging with flash dual-energy CT.Methods In total of 240 patients suspected with coronary heart disease were performed dual-energy CCTA(DE-CCTA)and were divided into four groups according to the A tube electric current and the methods of reconstruction,including group A(conventional group:180 mAs+FBP)and low-dose groups(including group B,C,D:1 50 mAs,120 mAs,90 mAs +SAFIRE,respectively).The mean of CT value, image noise,SNR,CNR,image quality and radiation dosage were compared among the four groups.Among the patients,52 cases with coronary artery stenosis which were diagnosised by DE-CCTA were also confirmed by CAG,and the consistency of these two methods in the diagnosis of coronary artery stenosis were compared.Results The scores of all image quality were more than 3 points and were statistically significant among the four groups(P <0.05).The mean of CT value is not statistically significant (P >0.05), while the image noise,SNR,CNR and the radiation dosage were statistically significant (P <0.05)among the four groups.The ED of group D was lower 55.62% than group A.DE-CCTA and CAG in the diagnosis of coronary artery stenosis had satisfactory consistency (Kappa=0.84,P<0.05).Conclusion Low-dose coronary artery DE-CCTA not only have none affect of image quality and diagnostic accuracy, but also can significantly reduce the radiation dosage.