Enhancing Surface Strain of Intermetallic Fuel Cell Catalysts by Composition-Induced Phase Transition.

The lattice parameter of platinum-based intermetallic compounds (IMCs), which correlates with the intrinsic activity of the oxygen reduction reaction (ORR), can be modulated by crystal phase engineering. However, the controlled preparation of IMCs with unconventional crystal structures remains highly challenging. Here, we demonstrate the synthesis of carbon-supported PtCu-based IMC catalysts with an unconventional L10 structure by a composition-regulated strategy. Experiment and machine learning reveal that the thermodynamically favorable structure changes from L11 to L10 when slight Cu atoms are substituted with Co. Benefiting from crystal-phase-induced strain enhancement, the prepared L10-type PtCu0.8Co0.2 catalyst exhibits much-enhanced mass and specific activities of 1.82 A mgPt-1 and 3.27 mA cmPt-2, which are 1.91 and 1.73 times higher than those of the L11-type PtCu catalyst, respectively. Our work highlights the important role of crystal phase in determining the surface strain of IMCs, and opens a promising avenue for the rational preparation of IMCs with different crystal phases by doping.

Beneficial Effects of Bushen Formula Combined with Enticavir on Chronic Hepatitis B Patients with Suboptimal Response to Enticavir by Regulating B-Cell Differentiation.

BACKGROUND/AIMS: To investigate the clinical effects of the combination therapy with Bushen Formula (BSF) plus enticavir (ETV) on chronic hepatitis B (CHB) patients with suboptimal response to ETV and explore the regulatory mechanisms of BSF on B cells-mediated humoral immunity. METHODS: Sixty-four HBeAg-positive CHB patients with suboptimal response to ETV were enrolled, and were randomly assigned into control group (C-Group, placebo combined with ETV for 12 months) or treatment group (T-Group, BSF combined with ETV for 12 months). Serum samples from 57 treatment-naïve CHB patients and 15 healthy controls were collected. Serum HBV DNA levels were evaluated by real-time PCR. Characteristics of peripheral blood B-cell subtypes were analyzed by flow cytometry. Serum HBV markers and B cell-activating factor (BAFF) levels were detected by ELISA. Chinese medicine symptom complex score was evaluated and recorded. RESULTS: After treatment, the rates of patients with a reduction of HBsAg > 0.5 log10 IU/ml or 1.0 log10 IU/ml and the rates of HBeAg clearance in T-Group were all higher than those in C-group, with no significant intergroup difference. Only in T-Group, Chinese medicine symptom complex score and the frequency of total B cells were significantly decreased, and the frequencies of Bm1, CD24+CD27-switched B cells and plasma cells were markedly increased after treatment compared with those before treatment. Compared with healthy controls, serum BAFF levels in treatment-naïve CHB patients were increased, and there was a significant positive correlation between serum BAFF and HBsAg levels. However, serum BAFF levels did not differ after treatment in T-Group and C-Group. CONCLUSIONS: The combination therapy with BSF plus ETV promotes the reduction of HBsAg level and the clearance of HBeAg in CHB patients with partial response to ETV through regulating the differentiation of B-cell subsets.

Hepatitis B core antigen upregulates B7-H1 on dendritic cells by activating the AKT/ERK/P38 pathway: a possible mechanism of hepatitis B virus persistence.

B7-H1 binding to programmed death-1 may deliver a coinhibitory signal to T cells that is involved in the regulation of T-cell activation and tolerance. B7-H1 plays a key role in dysfunction of dendritic cells (DCs) during chronic HBV infection, but the expression mechanism of B7-H1 remains unclear. One hundred and twenty-nine patients with chronic HBV infection were categorized into either the immune tolerance phase (HBV-IT), the immune clearance phase (HBV-IC), or the inactive carrier phase (HBV-IA). Twenty healthy volunteers were enrolled as controls. Another 16 patients with HBeAg-positive chronic Hepatitis B were enrolled, and entecavir was administrated at 0.5 mg per day for 6 months. The B7-H1 expression level on peripheral DCs was tested by flow cytometry. In vitro, expression levels of B7-H1 and signaling molecules on monocyte-derived DC (MO-DC) induced by recombinant hepatitis B virus C antigen (rhHBcAg) were examined by RT-PCR, flow cytometry, and western blotting, and the apoptosis rate was tested by flow cytometry. The percentages of peripheral DCs and myeloid DCs (mDCs) were decreased and B7-H1 levels were increased in patients compared with controls. Serum HBV-DNA levels were positively correlated with B7-H1 levels on mDCs in patients with HBV-IT. B7-H1 levels on peripheral DCs from patients with chronic hepatitis B decreased after antiviral therapy. In vitro studies demonstrated that the B7-H1 level on MO-DC was upregulated by rhHBcAg, which resulted from the activation of PI3K-AKT, ERK, and P38 signaling pathways, and the percentage of MO-DC was downregulated by rhHBcAg. In addition, rhHBcAg promoted the apoptosis of MO-DC. The data suggest that HBcAg induced B7-H1 upregulation by activating AKT, ERK, and P38 signaling pathways, which inhibited the clearance of HBV-DNA and the reduction of DCs contributed to immune tolerance, which may correlate with apoptosis.

High intensity focused ultrasound treatment for patients with local advanced pancreatic cancer.

BACKGROUND/AIMS: To evaluate the safety and efficacy of high intensity focused ultrasound (HIFU) therapy in patients with local advanced pancreatic cancer. METHODOLOGY: 39 patients with local advanced pancreatic cancer were treated with HIFU, including 26 male and 13 female patients. The locations of the tumours were as follows: head of pancreas in 7 patients, body and/or tail of pancreas in 32 patients. Pain relief, time to progression (TTP), median survival and complications were analysed after HIFU treatment. RESULTS: There were no severe complications or adverse events related to HIFU therapy in any of the patients treated. Pain relief was achieved in 79.5% of patients. Median TTP was 5.0 months. The median overall survival time was 11 months. 6-month and 1-year survival rate for patients were 82.1% and 30.8% respectively. CONCLUSIONS: Although this study may have limitations, preliminary results demonstrate the safetyof clinical application of HIFU for pancreatic cancer and reveal it to be a promising mode of treatment for local advanced pancreatic cancers.

Promoting ordering degree of intermetallic fuel cell catalysts by low-melting-point metal doping.

Carbon supported intermetallic compound nanoparticles with high activity and stability are promising cathodic catalysts for oxygen reduction reaction in proton-exchange-membrane fuel cells. However, the synthesis of intermetallic catalysts suffers from large diffusion barrier for atom ordering, resulting in low ordering degree and limited performance. We demonstrate a low-melting-point metal doping strategy for the synthesis of highly ordered L10-type M-doped PtCo (M = Ga, Pb, Sb, Cu) intermetallic catalysts. We find that the ordering degree of the M-doped PtCo catalysts increases with the decrease of melting point of M. Theoretic studies reveal that the low-melting-point metal doping can decrease the energy barrier for atom diffusion. The prepared highly ordered Ga-doped PtCo catalyst exhibits a large mass activity of 1.07 A mgPt-1 at 0.9 V in H2-O2 fuel cells and a rated power density of 1.05 W cm-2 in H2-air fuel cells, with a Pt loading of 0.075 mgPt cm-2.

HBcAg induces PD-1 upregulation on CD4+T cells through activation of JNK, ERK and PI3K/AKT pathways in chronic hepatitis-B-infected patients.

Hyper-expression of programmed death-1 (PD-1) is a hallmark of exhausted T cells. In chronic hepatitis-B virus (HBV)-infected patients, PD-1 upregulation on T cells was often observed. The mechanism of it has not been fully understood. In this study, we examined the dynamic changes of PD-1 expression on T cells during the natural history of chronic HBV infection and explored the signaling pathway of PD-1 upregulation by the hepatitis-B core antigen (HBcAg). Sixty-seven chronic HBV-infected patients were categorized into an immune tolerance group, an immune clearance group and an inactive virus carrier group, and 20 healthy volunteers were chosen as normal control group. Peripheral blood mononuclear cells from patients and healthy volunteers, and T lymphocytes from healthy volunteers were separated. Results showed that the PD-1 expression level on CD4(+)T cells in every phase of chronic HBV infection was significantly higher than that in healthy volunteers, whereas such effects were not observed on CD8(+)T cells. In the immune clearance phase, a positive correlation was found between serum HBV DNA level and the PD-1 expression level on CD4(+)T cells. In all phases, no correlation was shown between serum alanine amino transferase (ALT) level and PD-1 expression level. Phosphorylation of JNK, ERK and AKT was induced by HBcAg, and inhibitors of JNK, ERK and PI3K/AKT significantly decreased the HBcAg-induced PD-1 upregulation on CD4(+)T cells. In conclusion, the PD-1 expression level on CD4(+)T cells was upregulated in every phase of chronic HBV infection, which was induced by HBcAg through JNK, ERK and PI3K/AKT signaling pathways.

Classical eyeblink conditioning using electrical stimulation of caudal mPFC as conditioned stimulus is dependent on cerebellar interpositus nucleus in guinea pigs.

AIM: To determine whether electrical stimulation of caudal medial prefrontal cortex (mPFC) as conditioned stimulus (CS) paired with airpuff unconditioned stimulus (US) was sufficient for establishing eyeblink conditioning in guinea pigs, and whether it was dependent on cerebellar interpositus nucleus. METHODS: Thirty adult guinea pigs were divided into 3 conditioned groups, and trained on the delay eyeblink conditioning, short-trace eyeblink conditioning, and long-trace eyeblink conditioning paradigms, respectively, in which electrical stimulation of the right caudal mPFC was used as CS and paired with corneal airpuff US. A pseudo conditioned group of another 10 adult guinea pigs was given unpaired caudal mPFC electrical stimulation and the US. Muscimol (1 µg in 1 µL saline) and saline (1 µL) were infused into the cerebellar interpositus nucleus of the animals through the infusion cannula on d 11 and 12, respectively. RESULTS: The 3 eyeblink conditioning paradigms have been successfully established in guinea pigs. The animals acquired the delay and short-trace conditioned responses more rapidly than long-trace conditioned responses. Muscimol infusion into the cerebellar interpositus nucleus markedly impaired the expression of the 3 eyeblink conditioned responses. CONCLUSION: Electrical stimulation of caudal mPFC is effective CS for establishing eyeblink conditioning in guinea pigs, and it is dependent on the cerebellar interpositus nucleus.

Corrigendum to "Immunomodulatory Effects of Combination Therapy with Bushen Formula plus Entecavir for Chronic Hepatitis B Patients".

[This corrects the article DOI: 10.1155/2019/8983903.].

Atractylenolide III ameliorates Non-Alcoholic Fatty Liver Disease by activating Hepatic Adiponectin Receptor 1-Mediated AMPK Pathway.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver diseases worldwide. At present, there are no effective pharmacological therapies for NAFLD except lifestyle intervention-mediated weight loss. Atractylenolide III (ATL III), the major bioactive component found in Atractylode smacrocephala Koidz, has been shown to exert anti-oxidant, anti-tumor, anti-allergic response, anti-bacterial effects and cognitive protection. Here we investigate the therapeutic potential and underlying mechanisms of ATL III for the treatment of NAFLD. Methods: Male C57BL/6J mice were fed a high-fat diet (HFD) and treated with ATL III. Lipid accumulation was analyzed by Oil Red O staining in liver tissues and free fatty acids (FFAs)-treated hepatocytes. AMP-activated protein (AMPK) and sirtuin 1(SIRT1) signaling pathways were inhibited by Compound C and EX527 in vitro, respectively. Small-interfering RNA (siRNA) was used to knockdown adiponectin receptor 1 (AdipoR1) expression in HepG2 cells. Results: ATL III treatment ameliorated liver injury and hepatic lipid accumulation in the HFD-induced NAFLD mouse model as demonstrated by that ATL III administration significantly reduced serum levels of alanine aminotransferase, glutamic oxaloacetic transaminase, triglycerides, total cholesterol and low-density lipoprotein. Furthermore, treatment with ATL III alleviated hepatic oxidative stress, inflammation and fibrosis in the HFD feeding model. To study the underlying mechanisms, we performed Computer Aided Design assay and found that open-formed AdipoR1 and adiponectin receptor 2 were the potential receptors targeted by ATL III. Interestingly, HFD feeding or FFAs treatment only reduced hepatic AdipoR1 expression, while such reduction was abolished by ATL III administration. In addition, in vitro treatment with ATL III activated the AdipoR1 downstream AMPK /SIRT1 signaling pathway and reduced lipid deposition in HepG2 cells, which was diminished by silencing AdipoR1. Finally, inhibition of AMPK or SIRT1, the AdipoR1 downstream signaling, abolished the protective effects of ATL III on lipid deposition and oxidative stress in FFAs-treated HepG2 cells. Conclusion: Our findings suggest that ATL III is a therapeutic drug for the treatment of NAFLD and such protective effect is mediated by activating hepatic AdipoR1-mediated AMPK/SIRT1 signaling pathway.

Bushen Jianpi Formula Combined with Entecavir for the Treatment of HBeAg-Negative Chronic Hepatitis B: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Bushen Jianpi formula (BSJPF, also known as Lingmao formula) is a traditional Chinese medicine for chronic hepatitis B (CHB). The previous study has suggested that the treatment combination of BSJPF and entecavir (ETV) can achieve a significant loss of hepatitis B e antigen (HBeAg) and a significant decrease in serum level of hepatitis B virus (HBV) DNA in HBeAg-positive CHB patients with mildly elevated alanine aminotransferase. Objective: This study aimed to evaluate the efficacy and safety of BSJPF combined with ETV for treating HBeAg-negative CHB patients. Methods: A total of 640 patients were assigned randomly to the treatment group (receiving BSJPF combined with ETV for 96 weeks) or the control group (receiving a placebo combined with ETV for 96 weeks) in a 1 : 1 ratio. The primary endpoints are the rate of loss of hepatitis B surface antigen (HBsAg). The secondary outcomes included the rate of decrease in the HBsAg concentration to ≥1 lg·IU/mL, the HBV DNA suppression, the decline of the level of covalently closed circular DNA (cccDNA) in the liver, histological improvements, and the rate of ALT normalization. Results: The rate of HBsAg loss in the treatment group was significantly higher than that of the control group (5.5% versus 1.8%, P=0.031). There were 11.1% of patients in the treatment group who recorded a reduction in HBsAg ≥1 lg·IU/mL, which is better than 5.9% of patients in the control group (P=0.043). There was no significant difference between the two groups with regard to the rate of HBV DNA clearance, the reduction in intrahepatic cccDNA, and the rate of ALT normalization (P > 0.05). The rate of liver fibrosis improvement in the treatment group was better than that of the control group (35.5% versus 11.8%, P=0.031), but there was no difference in necroinflammatory improvement (P > 0.05). The adverse events (AEs) were similar between the two groups, except for the abnormal kidney function, with 2.2% in the control group and 0.0% in the treatment group (P=0.028). Conclusion: The combination of BSJPF and ETV can increase the rate of HBsAg loss and the rate of histological fibrosis improvement without serious adverse events in CHB patients. Trial Registration. This trial is registered with ChiCTR-IOR-16009880 on November 16, 2016-retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=16836.

[Study of xiaozhang recipe combined with lamivudine in treatment of 84 chronic viral hepatitis B patients with compensated liver cirrhosis].

OBJECTIVE: To assess the clinical efficacy of Xiaozhang Recipe (XR) in treatment of chronic viral hepatitis B patients with compensated liver cirrhosis. METHODS: Based on the anti-viral effects of lamivudine, 84 chronic viral hepatitis B patients with compensated liver cirrhosis were randomly assigned to the treatment group and the control group. Patients in the treatment group were treated with XR (consisting of heterophylla falsestarwort root, large head atractylodes rhizome, tangerine peel, green tangerine peel, water-plantain tuber, bugleweed herb, turtle shell, oyster shell, chicken's gizzard-skin endothelium, areca peel, decocted, one dose daily, twice daily). Patients in the control group took Fuzheng Huayu Capsule (consisting of red sage root, walnut seed, gynostemma pentaphyllum, aweto, magnoliavine fruit; five pills each time, three times daily, 30 min before meals). The therapeutic course for all was 12 months. The changes of the Chinese medicine symptom scores, chronic liver disease questionnaire (CLDQ), the liver function, hepatitis B virus deoxyribonucleic acid (HBV DNA) were compared between before and after treatment in the two groups. Meanwhile, B ultrasound was performed on all patients. Changes of the inner diameter of the portal vein and the splenic vein, the length and the thickness of the spleen were recorded. RESULTS: After treatment the Chinese medicine symptom scores and CLDQ obviously decreased in the two groups (P<0.01). Besides, the score in the treatment group decreased more obviously than that in the control group (P<0.05, P<0.01). The Child-Pugh scores obviously decreased in the two groups (P<0.01). However, the comparison between the two groups did not show any statistical significance (P>0.05). The liver function of of the two groups were improved when compared with before treatment (P<0.01), and the treatment group was superior to the control group (P<0.01). The B ultrasound results showed MPV, SPV, the length and the thickness of the spleen obviously decreased in the treatment group (P< 0.01). Only the thickness of the spleen obviously decreased in the control group (P<0.01). The HBV DNA obviously decreased in the two groups (P<0.01), more obviously shown in the treatment group (P<0.01). CONCLUSIONS: XR in combination of lamivudine could improve the liver function of chronic viral hepatitis B patients with compensated liver cirrhosis and HBV DNA, lower their Chinese medicine symptom scores and CLDQ scores, improve their Child-Pugh classification to some extent. It showed favorable effects.

The relation between aortic arch branching types and the location of large vessel occlusion in cardioembolic stroke.

Cardiac embolism is the leading etiology of ischemic strokes. There are arguments about the left-right propensity of cardioembolic strokes.This study aimed to reveal the relationship between the different aortic arch types and the location of large vessel occlusion (LVO) in cardioembolic stroke.We retrospectively identified all patients with acute ischemic stroke admitted to our comprehensive stroke center who had medium- to high-risk cardioembolicsources according to the TOAST classification.Only those with LVO and available images of the aortic arch were included. Patients were classified into 3 groups according to the aortic arch types: Type I (n = 44), Type II (n = 105), Type III (n = 36).The thrombus was divided into large thrombus or small thrombus based on the location of LVO.Overall, left-sided strokes (50.8%) were almost equal to right-sided (49.2%). There was a growing tendency for the percentage of left-sided infarcts with advancement of the aortic arch types either in the total cases or in the atrial fibrillation cases, with no statistical difference between the 3 aortic arch types.In type III aortic arch, left-sided strokes (69.0%) were twice than right-sided (31%) in large thrombus (P < 0.05), while right-sided strokes (85.7%) were more common than left-sided (14.3%) in small thrombus (P < 0.05).Conversely, in type Ⅰ and II aortic arches, left-sided strokes were more common than right-sided in small thrombus, while right-sided strokes were more common than left-sided in large thrombus (P < 0.05). The left-right propensity of cardioembolic stroke is related to the proximity of clot lodging in different aortic arch types.

Chemical characters and protective effect of Baqi Lingmao formula on experimental liver injury.

OBJECTIVE: To investigate the chemical characters of water-extract of Baqi Lingmao formula (BQLM formula) and its effects on anti-liver injury in model mice and live cells. METHODS: BQLM formula was composed of ten herbal medicines. We determined the contents of alkaloids, saponins, phenolic acids and flavonoid in BQLM formula by UV spectrophotometry. The active components of alkaloids and phenolic acids in BQLM formula were identified by HPLC chromatography. The anti-hepatic injury effects of BQLM formula were investigated with concanavalin A (ConA)-induced hepatitis model of mice, human liver LO2 and HepG2.2.15 cells. RESULTS: BQLM formula (2 and 10 g/kg, orally) significantly improved the damages of liver tissues and functions caused by ConA in mice, reduced the infiltration of inflammatory cells into liver and inhibited the inflammatory cytokine secretion of interferon-γ, tumor necrosis factor-α and interleukin-6. BQLM formula simultaneously decreased the levels of alanine aminotransferase and aspartate aminotransferase of liver and serum, and recovered the superoxide dismutase and catalase activities of liver to normal levels in ConA-induced hepatic-injury mice. The serum of BQLM formula group stimulated the human liver LO2 cell proliferation in vitro. Further, BQLM formula obviously promoted the proliferation of normal hepatocytes (LO2 cells) and inhibited the hepatocytes death induced by ConA. It also significantly inhibited the proliferation of HepG2.2.15 cells and decreased the secretion of HBsAg and HBeAg in vitro. CONCLUSIONS: BQLM formula has anti-inflammation and anti-hepatitis virus Beffects, and is capable of improving liver injury in vivo and in vitro.

[Clinical observation of transarterial chemoembolization combined with sorafenib for advanced hepatocellular carcinoma].

OBJECTIVE: To observe the efficacy and side effects of transarterial chemoembolization (TACE) combined with sorafenib for advanced hepatocellular carcinoma (HCC). METHODS: Forty patients with HCC were treated with sorafenib (400 mg bid) after TACE. The efficacy was evaluated according to RECIST 1.1 criteria, and side effects were assessed by NCI CTC 3.0 criteria. RESULTS: Among the forty cases, one case achieved complete remission (CR), seven cases achieved partial remission (PR), nineteen cases achieved stable disease (SD) and thirteen cases had progressive disease (PD). The disease control rate (DCR) was 67.5%. The overall survival time was 1 - 18 months, and 1-year survival rate was 54.0%. The major adverse events were hand-foot skin reaction, diarrhea and thrombocytopenia. CONCLUSION: The combined therapy of TACE and sorafenib is effective and well tolerated for advanced HCC.

[Value of protective stoma in intersphincteric resection for ultra-low rectal cancer].

OBJECTIVE: To investigate the value of protective stoma in intersphincteric resection (ISR) for ultra-low rectal cancer. METHODS: Clinical data of 56 ultra-low rectal cancer patients without involvement of external anal sphincter treated during January 1999 to July 2009 with trans-anal ISR plus trans-abdominal total mesorectum excision and coloanal anastomosis were retrospectively analyzed. The patients were divided into two groups based on whether they received protective ostomy: ostomy group (16 cases) and ostomy-free group (40 cases). The postoperative complications as well as anal functional restoration were compared between the two groups. RESULTS: Sixteen cases (32.1%) of the 56 patients received protective stoma. The complication rate of anastomosis and anus complication rate in the ostomy-free group were significantly higher than those in ostomy group [35.0% (14/40) and 40.0% (16/40) vs. 1/16 and 1/16; P < 0.05]. In the ostomy-free group, one patient developed anastomotic dehiscence and tumor recurrence, the patients was given permanent colostomy, and the other three patients with lesions in the anastomosis and anus received ostomy and secondary surgical treatment, with a reoperation rate of 10.0% (4/40). The anal function of patients in the two groups were both decreased after the operation. The rate of patients got Kirwan grade I anal sphincter function in the 3rd, 6th and 12th month after protective stoma operation was 11/16, 13/15 and 11/13 in the ostomy group, respectively; and those were 30.0%, 37.5% and 45.0% in the ostomy-free group, respectively. Anal function was significantly better in the ostomy group than that in the ostomy-free group during the same postoperative period (P < 0.05). CONCLUSION: Protective stoma can avoid anastomotic leakage following ISR for ultra-low rectal cancer, and alleviate the suffering of anal incontinence in the early postoperative period, and is conducive to the restoration of anal function.

[Surgical intervention and radiotherapy outcome of solitary plasmacytoma of cervical spine].

OBJECTIVE: To study the clinical features, treatment methods and outcome of solitary plasmacytoma of cervical spine. METHODS: From January 1995 to December 2007, the data of 23 cases with solitary plasmacytoma of cervical spine was analyzed. There were 16 males and 7 females (mean age 56 years, range: 32 - 76 years). Two cases underwent radiotherapy alone and 21 patients received surgery. According to WBB staging system, surgical procedures were defined as total or subtotal resection (6 cases), appendix resection (4 cases), sagittal resection (3 cases) and total spondylectomy (8 cases). All surgical cases were managed using an anterior approach, posterior approach or combined anterior and posterior approach. The cervical spinal reconstruction was achieved through anterior cervical titanium plate and titanium mesh cage filled with auto iliac graft or bone cement, or anterior and posterior combined instrumented fusion. All patients received radiotherapy as adjunctive therapy. RESULTS: Follow-up of the 23 cases lasted 24.0 - 143.0 months (mean: 64.7 months). Neck pains obviously improved, and nerve compression symptoms disappeared or improved after surgery. Neurological function improved by 1 - 2 grades based on Frankel grading system. All the internal fixations were fused well and stability of the cervical spine was fine and no spine instability could be seen in our series. The bone graft fusion rate was 100%. During the follow-up period, 6 surgical cases had local recurrence and finally progressed to multiple myeloma (MM) and 3 died. Two cases without surgical treatment progressed to MM in 1 year and 1.5 years after confirmed diagnosis. They were given systemic chemotherapy. The other 15 patients had disease-free survival and after surgery and adjunctive radiotherapy. Obvious abnormity were not found in such examinations as M protein, bone marrow aspiration and emission computed tomography or PET-CT examinations. CONCLUSIONS: Solitary plasmacytoma of cervical spine is rarely seen clinically. Surgery is recommended as the primary management for patients with overt bone destruction and spinal instability or neurological dysfunction. Tumor excision with adjunctive radiotherapy can obviously reduce local recurrences and lower the possibility of progression to MM. The patients with progression to MM should receive chemotherapy according to chemotherapy protocol while the prognosis is comparatively worse.

Mechanism of Follicular Helper T Cell Differentiation Regulated by Transcription Factors.

Helping B cells and antibody responses is a major function of CD4+T helper cells. Follicular helper T (Tfh) cells are identified as a subset of CD4+T helper cells, which is specialized in helping B cells in the germinal center reaction. Tfh cells express high levels of CXCR5, PD-1, IL-21, and other characteristic markers. Accumulating evidence has demonstrated that the dysregulation of Tfh cells is involved in infectious, inflammatory, and autoimmune diseases, including lymphocytic choriomeningitis virus (LCMV) infection, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), IgG4-related disease (IgG4-RD), Sjögren syndrome (SS), and type 1 diabetes (T1D). Activation of subset-specific transcription factors is the essential step for Tfh cell differentiation. The differentiation of Tfh cells is regulated by a complicated network of transcription factors, including positive factors (Bcl6, ATF-3, Batf, IRF4, c-Maf, and so on) and negative factors (Blimp-1, STAT5, IRF8, Bach2, and so on). The current knowledge underlying the molecular mechanisms of Tfh cell differentiation at the transcriptional level is summarized in this paper, which will provide many perspectives to explore the pathogenesis and treatment of the relevant immune diseases.

Long-Term Traditional Chinese Medicine Combined with NA Antiviral Therapy on Cirrhosis Incidence in Chronic Hepatitis B Patients in the Real-World Setting: A Retrospective Study.

OBJECTIVE: To evaluate the impact of long-term Traditional Chinese Medicine (TCM) syndrome differentiation combined with antiviral therapy with Nucleos (t) ide analogues (NAs) on the incidence of cirrhosis in patients with chronic hepatitis B. METHODS: This retrospective cohort study included 521 patients with chronic hepatitis B who underwent a treatment course of ≥3 years from 1998-2019. Of the 521 patients, 261 were defined as TCM users while 260 were TCM nonusers (control group). All the enrolled subjects were followed up until February 2019 to measure the incidence and hazard ratio (HR) of cirrhosis, and the Cox proportional hazards regression model was used to analyze the independent factors affecting the occurrence of cirrhosis. RESULTS: The cumulative incidence of TCM users and nonusers was 6.9% and 13.5%, respectively (P=0.013). Results of the Kaplan-Meier analysis demonstrated that TCM users had a significantly lower cumulative incidence of cirrhosis than TCM nonusers (P=0.011), and TCM users had a significantly lower liver cirrhosis risk than TCM nonusers (adjusted HR = 0.416, 95% CI, 0.231-0.749). The histological evaluation revealed improved fibrosis in 45.0% of TCM users and 11.1% of TCM nonusers (P=0.033). The analysation of the prescriptions including total 119 single Chinese herbs medicinal demonstrated that "replenish qi and fortify the spleen," "clear heat and dispel dampness," and "soothe the liver and regulate qi" are the main treatment methods of TCM for CHB. CONCLUSIONS: Our study demonstrated that long-term TCM use may attenuate liver cirrhosis risk in patients with chronic hepatitis B (CHB).

Dual role of Ski in pancreatic cancer cells: tumor-promoting versus metastasis-suppressive function.

Ski used to be defined as an oncogene that contributes to the resistance of tumor cells to transforming growth factor-beta (TGF-beta)-induced growth arrest. As TGF-beta has a dual effect on tumor growth with both tumor-suppressing and -promoting activity depending on the stage of carcinogenesis and the cell type, the precise role of Ski in carcinogenesis remains unclear. In this study, we show that downregulation of Ski through lentivirus-mediated RNA interference decreases tumor growth both in vitro and in vivo, yet promotes cell invasiveness in vitro, and lung metastasis in vivo in the pancreatic cancer cell line SW1990, which contain wild-type Smad4 expression, and the BxPC3 cell line, which is Smad4 deficient. We also show that the downregulation of Ski increases TGF-beta-induced transcriptional activity, which is associated with increased TGF-beta-dependent Smad2/3 phosphorylation, and results in an altered expression profile of TGF-beta-inducible genes involved in metastasis, angiogenesis and cell proliferation and epithelial-mesenchymal transition. Immunohistochemical analysis of specimens from 71 patients with pancreatic adenocarcinoma showed a significant association between overexpression of Ski and decreased patient survival time (P = 0.0024). Our results suggest that Ski may act as a tumor proliferation-promoting factor or as a metastatic suppressor in human pancreatic cancer.

Low-level expression of Smad7 correlates with lymph node metastasis and poor prognosis in patients with pancreatic cancer.

BACKGROUND: Whether Smad7 acts as a tumor proliferation promoting factor or as a metastatic suppressor in human pancreatic cancer remains unclear. This study aims to determine the prognostic value of Smad7 in patients with pancreatic adenocarcinoma. METHODS: Surgical specimens obtained from 71 patients with pancreatic adenocarcinoma were immunohistochemically assessed for Smad7, Ki-67, MMP2, CD34, and Smad4 expression. The relationship between Smad7 expression and the clinicopathological characteristics of patients with pancreatic adenocarcinoma were also evaluated. RESULTS: Fifty-one of 71 specimens (71.8%) were Smad7 positive and 20 specimens were Smad7 negative. Negative expression of Smad7 correlated with lymph node metastasis, liver metastasis after surgery, and a poor survival rate (P = 0.0004, 0.0044, and 0.0003, respectively). We also found an inverse correlation between the expression of Smad7 and MMP2 (P = 0.0189). Multivariate analysis revealed that Smad7 expression was an independent prognostic factor [hazard ratio (HR) 0.3902; 95% confidence interval (CI) 0.1839-0.8277; P = 0.0142]. Furthermore, in both Smad4-negative and Smad4-positive groups, survival of patients with Smad7-positive tumors was significantly better than those with Smad7-negative tumors (both P < 0.0001). CONCLUSIONS: We conclude that low-level expression of Smad7 in pancreatic cancer is significantly associated with lymph node metastasis, high MMP2 expression, and poor prognosis.