[Bupleuri Radix-Paeoniae Radix Alba medicated plasma exerts effects on HepG2 hepatoma cells by regulating miR-1297/PTEN signaling axis].

The present study aimed to investigate the effect and mechanism of Bupleuri Radix-Paeoniae Radix Alba medicated plasma on HepG2 hepatoma cells by regulating the microRNA-1297(miR-1297)/phosphatase and tensin homologue deleted on chromosome 10(PTEN) signaling axis. Real-time quantitative PCR(RT-qPCR) was carried out to determine the mRNA levels of miR-1297 and PTEN in different hepatoma cell lines. The dual luciferase reporter assay was employed to verify the targeted interaction between miR-1297 and PTEN. The cell counting kit-8(CCK-8) was used to detect cell proliferation, and the optimal concentration and intervention time of the medicated plasma were determined. The cell invasion and migration were examined by Transwell assay and wound healing assay. Cell cycle distribution was detected by PI staining, and the apoptosis of cells was detected by Annexin V-FITC/PI double staining. The mRNA levels of miR-1297, PTEN, protein kinase B(Akt), and phosphatidylinositol 3-kinase(PI3K) were determined by RT-qPCR. Western blot was employed to determine the protein levels of PTEN, Akt, p-Akt, caspase-3, caspase-9, B-cell lymphoma-2(Bcl-2), and Bcl-2-associated X protein(Bax). The results showed that HepG2 cells were the best cell line for subsequent experiments. The dual luciferase reporter assay confirmed that miR-1297 could bind to the 3'-untranslated region(3'UTR) in the mRNA of PTEN. The medicated plasma inhibited the proliferation of HepG2 cells, and the optimal intervention concentration and time were 20% and 72 h. Compared with the blank plasma, the Bupleuri Radix-Paeoniae Radix Alba medicated plasma, miR-1297 inhibitor, miR-1297 inhibitor + medicated plasma all inhibited the proliferation, invasion, and migration of HepG2 cells, increased the proportion of cells in the G_0/G_1 phase, decreased the proportion of cells in the S phase, and increased the apoptosis rate. The medicated plasma down-regulated the mRNA levels of miR-1297, PI3K, and Akt and up-regulated the mRNA level of PTEN. In addition, it up-regulated the protein levels of PTEN, Bax, caspase-3, and caspsae-9 and down-regulated the protein levels of p-Akt, p-PI3K, and Bcl-2. In conclusion, Bupleuri Radix-Paeoniae Radix Alba medicated plasma can inhibit the expression of miR-1297 in HepG2 hepatoma cells, promote the expression of PTEN, and negatively regulate PI3K/Akt signaling pathway, thereby inhibiting the proliferation and inducing the apoptosis of HepG2 cells.

Human case of Anaplasma phagocytophilum infection in Eastern Taiwan.

Human granulocytic anaplasmosis (HGA) is a tick-borne infection caused by the bacterium Anaplasma phagocytophilum. In this study, we report an indigenous case of clinically diagnosed HGA. The patient was a 41-year-old man who experienced a tick bite and later developed fever, chills, myalgia, malaise, thrombocytopenia, leukocytosis with a left shift, elevated hepatic transaminase levels, and splenomegaly upon admission to the hospital. Immunofluorescence assays detected seroconversion against A. phagocytophilum, whereas tests for spotted fever group rickettsiae, murine typhus, scrub typhus, Q fever, and ehrlichiosis were negative. ELISA and Western blot analysis using recombinant MSP2 protein confirmed the exposure to A. phagocytophilum. Oral doxycycline and intravenous ceftriaxone were prescribed, and the patient made a full recovery. Our findings indicate the presence of HGA on the main island of Taiwan. Precautions against tick bites should be taken when engaging in outdoor activities, and HGA should be considered by physicians in the differential diagnosis.

Clinical application of gelatin sponge microparticles combined with pirarubicin for hepatic transcatheter arterial chemoembolization in breast cancer liver metastasis treatment: results of a single-center long-term study.

OBJECTIVE: To retrospectively analyze the safety and long-term clinical efficacy of gelatin sponge microparticles combined with the chemotherapy drug pirarubicin for hepatic transcatheter arterial chemoembolization (GSMs-TACE) in order to treat breast cancer liver metastasis (BCLM). METHODS: Twenty-seven BCLM patients who underwent GSMs-TACE from July 2010 to July 2016 were enrolled. Tumor target blood vessels were slowly and regionally embolized with absorbable gelatin sponge particles and pirarubicin injections. Plain computed tomography (CT) scans and biochemical indexes were re-examined at 4 days after treatment, and enhanced CT scans or magnetic resonance images and biochemical indexes, 1 month later. For patients with stable tumors, the follow-up period was 2 to 3 months, and the tumor response was evaluated using Modified Response Evaluation Criteria in Solid Tumors. Adverse reactions, survival time, and prognostic factors were assessed. RESULTS: By October 2019, 27 patients with BCLM had undergone GSMs-TACE, with an average of 2.44 ± 1.58 treatments. The 1-, 3-, and 5-year survival rates were 62.96%, 22.22%, and 14.81%, respectively, and the mOS was 22.0 months. No serious complications, such as acute liver failure and liver abscess, had occurred. There were two cases of acute cholecystitis that recovered after symptomatic treatment. Multivariate analysis of the prognosis showed that the primary tumor size, number of metastatic lymph nodes, estrogen receptor/progesterone receptor (ER/PR) status, and time to postoperative liver metastasis and combination therapy were statistically significant. CONCLUSIONS: The overall prognosis of BCLM was poor. GSMs-TACE was safe and effective for BCLM treatment and could prolong the median survival time of patients. Therefore, it is worthy of widespread clinical application.

Evaluation of radioactive 125I seed implantation for the treatment of refractory malignant tumours based on a CT-guided 3D template-assisted technique: efficacy and safety.

BACKGROUND: To observe the medium- and long-term clinical efficacy and safety of radioactive 125I seed implantation for refractory malignant tumours based on CT-guided 3D template-assisted technique. METHODS: Twenty-five patients with refractory malignant tumours who underwent radioactive 125I seed implantation based on CT-guided 3D template-assisted technique were selected. The post-operative adverse reactions were recorded. The number of puncture needles and particles used in the operation, dosimetric parameters, post-operative physical strength scores, and tumour response were statistically analysed. The overall survival time and survival rate were calculated, and the effect and prognosis were assessed. RESULTS: 125I seed implantation was successful in all patients without serious complications. The average number of implanted puncture needles was 17 (19.12 ± 13.00), and the median number of particles was 52 (55.12 ± 32.97). D90 in the post-operative clinical target volume (CTV) (93.24 ± 15.70 Gy) was slightly lower than that in the pre-operative CTV (93.92 ± 17.60 Gy; P > 0.05). The D90 in the post-operative planning target volume (PTV) (142.16 ± 22.25 Gy) was lower than the pre-operative PTV (145.32 ± 23.48 Gy; P > 0.05). The tumour responses at 6 months post-operatively: complete remission (CR), 20% (5/25); partial remission (PR), 48% (12/25); stable disease (SD), 24% (6/25); progressive disease (PD), 8% (2/25); CR + PR, 68% (17/25); and local control rate, 92% (23/25). The 6-, 12-, and 24-month survival rates were 100, 88, and 52%, respectively. The post-operative physical strength score (Karnofsky performance score, KPS) exhibited a gradual trend towards recovery, which rose to the highest value 12 months after implantation and then decreased slightly, but the average score was still > 90 points. There was one intra-operative pneumothorax, and two patients with superficial malignant tumours developed skin ulcerations. Multivariate analysis of prognosis showed that tumour sites and types were independent risk factors affecting survival. The number of needles and particles and template types were not the factors. CONCLUSIONS: 3D template combined with CT-guided radioactive 125I seed implantation can improve the rational distribution of radiation dose in the tumour target area because accurate radioactive 125I particle implantation was achieved. This technique has fewer complications and can further extend the overall survival and improve the quality of life. TRIAL REGISTRATION: Registration number: ChiCTR2000034566 2020/7/10 0:00:00 Retrospectively registered.

Choline Kinase α Mediates Interactions Between the Epidermal Growth Factor Receptor and Mechanistic Target of Rapamycin Complex 2 in Hepatocellular Carcinoma Cells to Promote Drug Resistance and Xenograft Tumor Progression.

BACKGROUND & AIMS: Choline kinase α (CHKA) catalyzes conversion of choline to phosphocholine and can contribute to carcinogenesis. Little is known about the role of CHKA in the pathogenesis of hepatocellular carcinoma (HCC). METHODS: We performed whole-exome and transcriptome sequence analyses of 9 paired HCC and non-tumor-adjacent tissues. We performed tissue chip analyses of 120 primary HCC and non-tumor-adjacent tissues from patients who received surgery in Shanghai, China from January 2006 through December 2009; 48 sets of specimens (HCC and non-tumor-adjacent tissues) were also analyzed. CHKA gene copy number was quantified and findings were validated by quantitative reverse transcription polymerase chain reaction analysis. CHKA messenger RNA and protein levels were determined by polymerase chain reaction, immunohistochemical, and immunoblot analyses. CHKA was examined in 2 hepatocyte cell lines and 7 HCC-derived cell lines, and knocked down with small interfering RNAs in 3 HCC cell lines. Cells were analyzed in proliferation, wound healing, migration, and invasion assays. Cells were injected into tail veins of mice and tumor growth and metastasis were quantified. Immunoprecipitation and immunofluorescence assays were conducted to determine interactions between CHKA and the epidermal growth factor receptor (EGFR) and the mechanistic target of rapamycin complex 2. RESULTS: Levels of CHKA messenger RNA were frequently increased in HCC tissues compared with nontumor tissues; increased expression was associated with amplification at the CHKA loci. Tumors that expressed high levels of CHKA had more aggressive phenotypes, and patients with these tumors had shorter survival times after surgery compared to patients whose tumors expressed low levels of CHKA. HCC cell lines that stably overexpressed CHKA had higher levels of migration and invasion than control HCC cells, and formed larger xenograft tumors with more metastases in mice compared to HCC cells that did not overexpress CHKA. CHKA was required for physical interaction between EGFR and mechanistic target of rapamycin complex 2. This complex was required for HCC cells to form metastatic xenograft tumors in mice and to become resistant to EGFR inhibitors. CONCLUSIONS: We found levels of CHKA to be increased in human HCCs compared to nontumor tissues, and increased expression to be associated with tumor aggressiveness and reduced survival times of patients. Overexpression of CHKA in HCC cell lines increased their invasiveness, resistance to EGFR inhibitors, and ability to form metastatic tumors in mice by promoting interaction of EGFR with mechanistic target of rapamycin complex 2.

Complete genome sequence of shrimp hemocyte iridescent virus (SHIV) isolated from white leg shrimp, Litopenaeus vannamei.

Infection with shrimp hemocyte iridescent virus (SHIV), a new virus of the family Iridoviridae isolated in China, results in a high mortality rate in white leg shrimp (Litopenaeus vannamei). The complete genome sequence of SHIV was determined and analyzed in this study. The genomic DNA was 165,809 bp long with 34.6% G+C content and 170 open reading frames (ORFs). Dotplot analysis showed that the longest repetitive region was 320 bp in length, including 11 repetitions of an 18-bp sequence and 3.1 repetitions of a 39-bp sequence. Two phylogenetic trees were constructed based on 27 or 16 concatenated sequences of proteins encoded by genes that are conserved between SHIV homologous and other iridescent viruses. The results of this study, suggest that SHIV should be considered a member of the proposed new genus "Xiairidovirus".

Epsc Involved in the Encoding of Exopolysaccharides Produced by Bacillus amyloliquefaciens FZB42 Act to Boost the Drought Tolerance of Arabidopsis thaliana.

Bacillus amyloliquefaciens FZB42 is a plant growth-promoting rhizobacteria that stimulates plant growth, and enhances resistance to pathogens and tolerance of salt stress. Instead, the mechanistic basis of drought tolerance in Arabidopsis thaliana induced by FZB42 remains unexplored. Here, we constructed an exopolysaccharide-deficient mutant epsC and determined the role of epsC in FZB42-induced drought tolerance in A. thaliana. Results showed that FZB42 significantly enhanced growth and drought tolerance of Arabidopsis by increasing the survival rate, fresh and dry shoot weights, primary root length, root dry weight, lateral root number, and total lateral root length. Coordinated changes were also observed in cellular defense responses, including elevated concentrations of proline and activities of superoxide dismutase and peroxidase, decreased concentrations of malondialdehyde, and accumulation of hydrogen peroxide in plants treated with FZB42. The relative expression levels of drought defense-related marker genes, such as RD29A, RD17, ERD1, and LEA14, were also increased in the leaves of FZB42-treated plants. In addition, FZB42 induced the drought tolerance in Arabidopsis by the action of both ethylene and jasmonate, but not abscisic acid. However, plants inoculated with mutant strain epsC were less able to resist drought stress with respect to each of these parameters, indicating that epsC are required for the full benefit of FZB42 inoculation to be gained. Moreover, the mutant strain was less capable of supporting the formation of a biofilm and of colonizing the A. thaliana root. Therefore, epsC is an important factor that allows FZB42 to colonize the roots and induce systemic drought tolerance in Arabidopsis.

Deciphering the anti-angiogenic effect of endostatin/cyclophosphamide to normalize tumor micrangium through notch signaling pathway in colon cancer.

BACKGROUND: The invasion of colon cancer is associated with the tumor angiogenesis. Endostatin is an important anti-angiogenic agent, and the additive effect of endostatin with a chemotherapeutic agent, cyclophosphamide, on micrangium has not been established. METHODS: Male BALB/c strain nude mice were injected with human colorectal carcinoma cells (HCT-116). The mice were divided into four groups (n=15, each group) and were treated with different concentrations of endostatin (15, 10, and 5 mg/kg/day), cyclophosphamide (20, 10, and 5 mg/kg/day), and combination of endostatin/cyclophosphamide (15+20, 15+10, and 15+5 mg/kg/day). The tumor inhibition rate was evaluated, followed by the quantification of messenger ribonucleic acid (mRNA) and protein expression of notch signaling components NOTCH-1, NOTCH-3, NOTCH-4, JAG-1, DLL-4, Hes-1, and Hey-1 using quantitative polymerase chain reaction (qPCR). The protein expression of NOTCH-3, JAG-1, and DLL-4 was confirmed using western blotting. Microvessel density (MVD) was evaluated to detect micrangium following the treatment. RESULTS: The endostatin/cyclophosphamide-treated samples exhibited an additive effect on the tumor inhibition rate and the microvessel count. NOTCH-1, NOTCH-3, NOTCH-4, JAG-1, Hes-1, and Hey-1 expression levels were highly correlated and downregulated in the treated samples, whereas DLL-4 expression was upregulated that accounted for its anti-angiogenic property. CONCLUSIONS: The combination treatment of colon cancer with endostatin and a chemotherapeutic agent, cyclophosphamide proves to be an efficient therapeutic strategy to inhibit the rapid vasculature formation confirmed by the differential expression of notch signaling components.

PTPN11/Shp2 overexpression enhances liver cancer progression and predicts poor prognosis of patients.

BACKGROUND & AIMS: We have previously reported that Shp2, a tyrosine phosphatase previously known as a pro-leukemogenic molecule, suppresses the initiation of hepatocellular carcinoma (HCC). However, the role of Shp2 in HCC progression remains obscure. METHODS: Shp2 expression was determined in human HCC using real-time PCR, immunoblotting and immunohistochemistry. Clinical significance of Shp2 expression was analyzed in 301 HCC tissues with clinico-pathological characteristics and follow-up information. Short hairpin RNA was utilized to investigate the function of Shp2 in hepatoma cell behavior. Role of Shp2 in HCC progression was monitored through nude mice xenograft assay. Kinase activity assay and co-immunoprecipitation were used for mechanism analysis. RESULTS: Elevated expression of Shp2 was detected in 65.9% (394/598) of human HCCs, and its levels were even higher in metastasized foci. Overexpression of Shp2 correlated well with the malignant clinico-pathological characteristics of HCC and predicted the poor prognosis of patients. Interference of Shp2 expression suppressed the proliferation of hepatoma cells in vitro and inhibited the growth of HCC xenografts in vivo. Down-regulation of Shp2 attenuated the adhesion and migration of hepatoma cells and diminished metastasized HCC formation in mice. Our data demonstrated that Shp2 promotes HCC growth and metastasis by coordinately activating Ras/Raf/Erk pathway and PI3-K/Akt/mTOR cascade. Moreover, down-regulation of Shp2 enhanced the sensitivity of hepatoma cells upon sorafenib treatment, and patients with low Shp2 expression exhibited superior prognosis to sorafenib. CONCLUSIONS: Shp2 promotes the progression of HCC and may serve as a prognostic biomarker for patients.

Pioglitazone, a PPARγ agonist, inhibits growth and invasion of human hepatocellular carcinoma via blockade of the rage signaling.

Pioglitazone (PGZ), a synthetic PPARγ ligand, is known to have anti-tumor activity. However, it is unclear how it acts against hepatocellular carcinoma (HCC). We hypothesized that the pathological receptor for advanced glycation end products (RAGE) is involved in the PGZ anti-tumor process. To test this notion, human primary HCC tissues and corresponding adjacent non-cancerous tissues (ANCT) from 75 consecutive cases were analyzed. The expression and clinical significance of RAGE was assessed by immunohistochemical assay through tissue microarray. After HCC cells were pretreated with different concentrations of PGZ, cell proliferation, apoptosis, cell invasion, and cell cycle distribution were evaluated by multiple assays. The results showed that, the positive expression of RAGE was significantly higher in HCC tissues than in ANCT (66.7% vs. 36.0%, P < 0.001), and was closely associated with pathological staging (P = 0.014) and lymph-vascular space invasion (P = 0.003). Moreover, PGZ inhibited proliferative activity and invasive potential, and induced apoptosis and cell cycle arrest in HCC cells resulting in increased expression of PPARγ and decreased expression of RAGE, NF-κB, HMGB1, p38MAPK, Ki-67, MMP-2, and CyclinD1. Furthermore, knockdown of RAGE or NF-κB by siRNA effectively suppressed cell proliferation and invasion, and mediated the inhibitory effects of PGZ in HCC cells. Taken together, our findings suggest that, RAGE is overexpressed in human HCC tissues, and is closely associated with the pathological staging and tumor invasion of HCC. In addition, PGZ as a PPARγ agonist may inhibit growth and invasion of HCC cells via blockade of the RAGE signaling.

MUC15 inhibits dimerization of EGFR and PI3K-AKT signaling and is associated with aggressive hepatocellular carcinomas in patients.

BACKGROUND & AIMS: Aberrant expression of MUC15 correlates with development of colorectal adenocarcinoma, and MUC15 has been reported to prevent trophoblast invasion of human placenta. However, little is known about the role of MUC15 in pathogenesis of hepatocellular carcinoma (HCC). METHODS: We analyzed HCC samples and matched nontumor liver tissues (controls) collected from 313 patients who underwent hepatectomy in Shanghai, China, from January 2006 through September 2009. Levels of messenger RNAs and proteins were determined by immunohistochemical, quantitative reverse transcription polymerase chain reaction, and immunoblot analyses. Statistical analyses were used to associate levels of MUC15 with tumor features and patient outcomes. RESULTS: Levels of MUC15 messenger RNA and protein were reduced in a greater percentage of HCC samples than control tissues. Tumors with reduced levels of MUC15 were more likely to have aggressive characteristics (eg, high levels of α-fetoprotein, vascular invasion, lack of encapsulation, and poor differentiation) than those with low levels. Patients whose tumors had reduced levels of MUC15 had shorter overall survival times (24 months vs 46 months for patients with tumors with high levels of MUC15) and time to disease recurrence. Stable expression of MUC15 in HCC cell lines (SMMC-7721 and HCC-LM3) reduced their proliferation and invasive features in vitro, and ability to form metastatic tumors in mice. MUC15 reduced transcription of the matrix metalloproteinases 2 and 7 increased expression of tissue inhibitor of metalloproteinase-2, which required phosphoinositide 3-kinase-v-akt murine thymoma viral oncogene homolog signaling. Physical interaction between MUC15 and epidermal growth factor receptor led to its relocation and degradation within early endosomes and was required for inactivation of phosphoinositide 3-kinase-v-akt murine thymoma viral oncogene homolog signaling. CONCLUSIONS: Reduced levels of MUC15 in HCCs are associated with shorter survival times of patients and reduced time to disease recurrence. Expression of MUC15 in HCC cells reduces their aggressive behavior in vitro and in mice by inducing dimerization of epidermal growth factor receptor and decreasing phosphoinositide 3-kinase signaling via v-akt murine thymoma viral oncogene homolog.

Palmitic acid induces autophagy in hepatocytes via JNK2 activation.

AIM: Free fatty acid-induced lipotoxicity plays a crucial role in the progression of nonalcoholic fatty liver disease (NAFLD). In the present study we investigated the effects of a high-fat diet and free fatty acids on the autophagic process in hepatocytes in vivo and in vitro and the underlying mechanisms. METHODS: LC3-II expression, a hallmark of autophagic flux, was detected in liver specimens from patients with non-alcoholic steatohepatitis (NASH) as well as in the livers of C57BL/6 mice fed a high-fat diet (HFD) up to 16 weeks. LC3-II expression was also analyzed in human SMMC-7721 and HepG2 hepatoma cells exposed to palmitic acid (PA), a saturated fatty acid. PA-induced apoptosis was detected by Annexin V staining and specific cleavage of PARP in the presence and absence of different agents. RESULTS: LC3-II expression was markedly increased in human NASH and in liver tissues of HFD-fed mice. Treatment of SMMC-7721 cells with PA increased LC3-II expression in time- and dose-dependent manners, whereas the unsaturated fatty acid oleic acid had no effect. Inhibition of autophagy with 3MA sensitized SMMC-7721 cells to PA-induced apoptosis, whereas activation of autophagy by rapamycin attenuated PA-induced PARP cleavage. The autophagy-associated proteins Beclin1 and Atg5 were essential for PA-induced autophagy in SMMC-7721 cells. Moreover, pretreatment with SP600125, an inhibitor of JNK, effectively abrogated PA-mediated autophagy and apoptosis. Specific knockdown of JNK2, but not JNK1, in SMMC-7721 cells significantly suppressed PA-induced autophagy and enhanced its pro-apoptotic activity; whereas specific knockdown of JNK1 had the converse effect. Similar results were obtained when HepG2 cells were tested. CONCLUSION: JNK1 promotes PA-induced lipoapoptosis, whereas JNK2 activates pro-survival autophagy and inhibits PA lipotoxicity. Our results suggest that modulation of autophagy may have therapeutic benefits in the treatment of lipid-related metabolic diseases.

[Functions of T lymphocytes mediated by in vitro dendritic cells of chronic HBV infection patients in different immune states: a clinical research].

OBJECTIVE: To explore the improvement of dendritic cells' (DCs) functions in chronic hepatitis B (CHB) patients by two different drugs plasma, i.e., Shen supplementing and detoxification (SSD) and Pi invigorating and detoxification (PID), thus comparing which method was more effective to activate DCs to improve T lymphocyte functions. METHODS: Totally 30 CHB outpatients were recruited. They were assigned to the immune tolerant group and the immune clearance group, 15 in each group. Totally 60 mL peripheral blood was extracted to isolate and develop mature DCs. Chinese compound containing (Liuwei Ganlu Syrup for SSD) and (Sijun Ganlu Syrup for PID) plasma were added to promote the maturation of DCs on the 7th day. Besides, non-drug plasma was taken as the control. On the ninth day, HBV core 18-27 loaded core peptide and its own T lymphocyte were co-cultivated for 72 h. Then T lymphocytes were collected. The expression levels of CD3, CD28, CD4, and CD8, programmed death-1 (PD-1) were detected using flow cytometry. RESULTS: Compared with non-drug plasma, the expression levels of CD3, CD4, and CD28 could be improved, and the expression levels of CD8 and PD-1 could be reduced by the two methods, showing statistical difference (P < 0.05). Besides, SSD containing plasma showed better effect in improving the molecular CD28 expression rate, and reducing the molecular PD-1 expression rate on the T cell surface, showing statistical difference when compared with that of PID containing plasma (P < 0.05). CONCLUSIONS: In vitro intervention of DCs by SSD and PID containing plasmas combined co-cultivation of its own T lymphocytes could promote the activation of DCs to improve the function of T cells and the expression of T cell surface molecules. Besides, SSD showed more significant effect on infection immune of HBV patients in the tolerance stage.

In vivo knockdown of hippocampal miR-132 expression impairs memory acquisition of trace fear conditioning.

MicroRNA-132 (miR-132) has been demonstrated to affect multiple neuronal functions, including dendritic growth and spinogenesis in cultured neurons and brain slices, as well as learning behavior of animals. However, its role in acquisition of temporal-associated memory remains unclear. In this study, we demonstrated that the mature miR-132 level in mouse hippocampus was significantly increased at 30 min after trace fear conditioning, a type of temporal-associated learning, and returned to baseline values in 2 h. We then knocked down miR-132 expression in vivo by infusing a lentivector expressing anti-miR-132 hairpin RNA into the third ventricle near the anterior hippocampi such RNA diffused laterally to both hippocampal formations, later confirmed by histological analysis. This approach successfully reduced hippocampal miR-132 expression in both naïve and trace fear conditioned groups, and impaired acquisition of trace fear memory in mice. To our knowledge, this result is the first demonstration of change in temporal learning behavior by reducing microRNA (miRNA) level specifically in the hippocampal region.

Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients' poor recurrence-free survival after hepatectomy.

UNLABELLED: Survival of patients with hepatocellular carcinoma (HCC) remains poor, which is largely attributed to active angiogenesis. However, the mechanisms underlying angiogenesis in HCC remain to be discovered. In this study, we found that long noncoding RNA associated with microvascular invasion in HCC (lncRNA MVIH) (lncRNA associated with microvascular invasion in HCC) was generally overexpressed in HCC. In a cohort of 215 HCC patients, the overexpression of MVIH was associated with frequent microvascular invasion (P = 0.016) and a higher tumor node metastasis stage (P = 0.009) as well as decreased recurrence-free survival (RFS) (P < 0.001) and overall survival (P = 0.007). Moreover, the up-regulation of MVIH served as an independent risk factor to predict poor RFS. We also found that MVIH could promote tumor growth and intrahepatic metastasis by activating angiogenesis in mouse models. Subsequent investigations indicated that MVIH could activate tumor-inducing angiogenesis by inhibiting the secretion of phosphoglycerate kinase 1 (PGK1). Additionally, in 65 HCC samples, MVIH expression was inversely correlated with the serum level of PGK1 and positively correlated with the microvessel density. CONCLUSION: Deregulation of lncRNA MVIH is a predictor for poor RFS of HCC patients after hepatectomy and could be utilized as a potential target for new adjuvant therapies against active angiogenesis.

[Auxiliary treatment of HBV correlated hepatic failure by Chinese herbs: a systematic review of randomized controlled trials].

OBJECTIVE: To evaluate the effectiveness and safety of Chinese herbs as an adjuvant treatment for hepatitis virus B (HBV)-related hepatic failure. METHODS: Data were retrieved through the Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Library, PubMed, CNKI, VIP, Wanfang Database, and ChiCTR by key words or free words such as hepatic failure, severe hepatitis, HBV, Chinese medicine, randomization, and control. Appendix references of related papers were taken as supplementary indices. According to requirement for Cochrane systematic evaluation, randomized clinical trials on assessing the effectiveness and safety of Chinese herbs as main or adjuvant treatment in treating HBV-related hepatic failure were methodologically assessed, data extracted and analyzed. RESULTS: Totally 21 trials on Chinese herbal medicine therapy versus standard medical therapy (involving 1 881 patients) were included. Most trials had unclear risk bias. In 5 studies on the mortality, 3 trials showed that the mortality was lower in the test group than in the control group [RR 0.40, 95% CI (0.20, 0.79), P = 0.0002]. In 6 randomized control trials, totally 20 papers reported the control of complications. Eight results showed Chinese herbal medicine therapy had better effect in controlling complications. The recurrence rate and assessment of the survival quality were reported. Considering secondary indicators, four trials showed Chinese herbal medicine therapy had better effect in lowering the ineffective rate, decreasing total bilirubin (TBIL), and elevating prothrombin activity (PTA). Other prescriptive analyses found that the overall effect on secondary indicators was better in the test group than in the control group, but not all the indicators were statistically different. Adverse reactions were only reported in two papers, showing no severe adverse reaction. CONCLUSION: According to present evidence, till now, we could not judge whether Chinese herbs, as an adjuvant treatment, could do any favor for lowering the incidence and recurrence of hepatic failure patients, and improving their survival qualities.

[Professor SUN Shen-tian's experience in acupuncture treatment of depression based on "psychosomatic medicine"].

This paper introduces professor SUN Shen-tian's clinical thoughts and his characteristics of acupuncture techniques for the treatment of depression based on "psychosomatic medicine". Professor SUN, the master of traditional Chinese medicine, believes that depression refers to comorbidity of "heart mind" and "body", resulting from the "body-mind" disharmony, specially dominated by the emotional disorder. This disease is located in the brain, with the injury of mind and closely related to the heart and liver dysfunction. In pathogenesis, the dysfunction of brain mind and the unhealthy conditions of body and mind are involved. The treatment should focus on "regulating the mind, improving the intelligence, co-modulating the abdominal and brain functions and treating the physical and mental disorders". Baihui (GV 20), Ningshen (Extra) and emotional area on the head are selected as the main points to benefit the intelligence and calming down the mind; the abdominal region 1 and region 8 of "Sun's abdominal acupuncture" are used as the main points of the abdomen to regulate the brain functions. The point prescription is modified according to the symptoms and etiologies. The repeated transcranial acupuncture stimulation and electroacupuncture at low frequency (2 Hz) are crucial to the therapeutic effect. Reliving anxious emotions is specially considered before acupuncture, and the mind is protected and deqi is consolidated during acupuncture.

Efficacy and safety of CalliSpheres® microspheres drug-eluting beads transarterial chemoembolization in GCLM combined trans-arterial infusion therapy for treating primary focus of gastric cancer: a multi-center retrospective study.

BACKGROUND: The purpose of this study was to observe the safety and efficacy of CalliSpheres microspheres drug-eluting beads (DEB) transhepatic arterial chemoembolization (CSM-TACE) for liver metastasis of gastric cancer (GCLM) combined with trans-arterial infusion therapy (TAIT) as the primary focus of gastric cancer. RESEARCH DESIGN AND METHODS: Unresectable advanced GCLM patients were collected for retrospective analysis. Patients who progressed after chemotherapy or could not receive systematic chemotherapy were selected. CSM-TACE was used for GCLM treatment and oxaliplatin for TAIT of primary focus of gastric cancer. Adverse reactions, tumor reactions, survival rate, and survival time during treatment were recorded, and prognostic factors were analyzed. RESULTS: Forty-three patients from four oncology centers met inclusion criteria and were enrolled. CSM-TACE averaged (1.51 ± 0.51) times and TAIT averaged (4.58 ± 1.65) times. The follow-up time was 2.5-49 months, and the 6-month, 1-year, and 2-year survival rates were 86.0%, 72.1%, and 41.9%, respectively, with a median overall survival of 11.5 months. The adverse reactions during treatment were grade 1-3. The hazard ratio (HR) of combination therapy was 0.51 (P = 0.040), and the HR of TAIT frequency was 0.34 (P = 0.002), which were independent protective factors affecting prognosis. CONCLUSIONS: CSM-TAC for GCLM combined with TAIT for primary focus of gastric cancer is safe and efficacious, which is worthy of clinical promotion and application.

Efficacy and safety of CalliSpheres drug-eluting beads for bronchial arterial chemoembolization for refractory non-small-cell lung cancer and its impact on quality of life: A multicenter prospective study.

Objective: This study aimed to prospectively observe the efficacy and safety of CalliSpheres drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) for refractory non-small-cell lung cancer (NSCLC). Methods: The interventional therapy plan was as follows: 300-500 µm CalliSpheres drug-loaded microspheres were loaded with epirubicin, and then slow embolization of tumor supplying artery was performed after microcatheter superselection. Chest enhanced computed tomography and related hematological examination were reviewed after 2 months of DEB-BACE, and the tumor response after the first interventional therapy was evaluated using modified response evaluation criteria in solid tumors. The overall survival (OS) of patients was determined, and the quality of life and the incidence rate of adverse reactions were observed. Results: From January 2019 to January 2021, 43 patients with refractory NSCLC were enrolled. The patients were followed up until June 2022. All 43 patients underwent DEB-BACE 1.79 ± 0.69 times on average. The 3-, 6-, 12-, and 24-month survival rates were 100%, 86.0%, 41.9%, and 11.8%, respectively. The median OS was 11.5 months. After the first interventional treatment, cough and wheezing significantly improved in 31 patients, hemoptysis was effectively controlled in 12 patients, and superior vena cava compression disappeared in 2 patients after 2 times of treatment. The general health status of the patients after treatment significantly improved compared with that before treatment, including the improvement in physical and emotional functions. Fatigue, nausea and vomiting, dyspnea, and insomnia improved significantly after treatment. No serious adverse events, such as spinal cord injury and cerebral embolism, were observed during the perioperative period. The main adverse reaction after DEB-BACE was chest pain (13/43, grade 1) followed by fever (10/43, grade 1-2), which was significantly relieved within 3-5 days after symptomatic treatment. Other adverse reactions included irritating cough, nausea and vomiting, and bone marrow suppression, and the incidence was less than 20%. Conclusions: DEB-BACE was effective and safe in treating refractory NSCLC, which could significantly improve patients' quality of life and was worthy of clinical promotion and application.

Mesaconine alleviates doxorubicin-triggered cardiotoxicity and heart failure by activating PINK1-dependent cardiac mitophagy.

Aberrant mitophagy has been identified as a driver for energy metabolism disorder in most cardiac pathological processes. However, finding effective targeted agents and uncovering their precise modulatory mechanisms remain unconquered. Fuzi, the lateral roots of Aconitum carmichaelii, shows unique efficacy in reviving Yang for resuscitation, which has been widely used in clinics. As a main cardiotonic component of Fuzi, mesaconine has been proven effective in various cardiomyopathy models. Here, we aimed to define a previously unrevealed cardioprotective mechanism of mesaconine-mediated restoration of obstructive mitophagy. The functional implications of mesaconine were evaluated in doxorubicin (DOX)-induced heart failure models. DOX-treated mice showed characteristic cardiac dysfunction, ectopic myocardial energy disorder, and impaired mitophagy in cardiomyocytes, which could be remarkably reversed by mesaconine. The cardioprotective effect of mesaconine was primarily attributed to its ability to promote the restoration of mitophagy in cardiomyocytes, as evidenced by elevated expression of PINK1, a key mediator of mitophagy induction. Silencing PINK1 or deactivating mitophagy could completely abolish the protective effects of mesaconine. Together, our findings suggest that the cardioprotective effects of mesaconine appear to be dependent on the activation of PINK1-induced mitophagy and that mesaconine may constitute a promising therapeutic agent for the treatment of heart failure.