Observation of plaid-like spin splitting in a noncoplanar antiferromagnet.

Spatial, momentum and energy separation of electronic spins in condensed-matter systems guides the development of new devices in which spin-polarized current is generated and manipulated1-3. Recent attention on a set of previously overlooked symmetry operations in magnetic materials4 leads to the emergence of a new type of spin splitting, enabling giant and momentum-dependent spin polarization of energy bands on selected antiferromagnets5-10. Despite the ever-growing theoretical predictions, the direct spectroscopic proof of such spin splitting is still lacking. Here we provide solid spectroscopic and computational evidence for the existence of such materials. In the noncoplanar antiferromagnet manganese ditelluride (MnTe2), the in-plane components of spin are found to be antisymmetric about the high-symmetry planes of the Brillouin zone, comprising a plaid-like spin texture in the antiferromagnetic (AFM) ground state. Such an unconventional spin pattern, further found to diminish at the high-temperature paramagnetic state, originates from the intrinsic AFM order instead of spin-orbit coupling (SOC). Our finding demonstrates a new type of quadratic spin texture induced by time-reversal breaking, placing AFM spintronics on a firm basis and paving the way for studying exotic quantum phenomena in related materials.

A radiomics model based on magnetic resonance imaging to predict cytokeratin 7/19 expression and liver fluke infection of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. HCC with liver fluke infection could harbor unique biological behaviors. This study was aimed at investigating radiomics features of HCC with liver fluke infection and establishing a model to predict the expression of cytokeratin 7 (CK7) and cytokeratin 19 (CK19) as well as prognosis at the same time. A total of 134 HCC patients were included. Gadoxetic acid-enhanced magnetic resonance imaging (MRI) images of all patients were acquired. Radiomics features of the tumor were extracted and then data dimensionality was reduced. The radiomics model was established to predict liver fluke infection and the radiomics score (Radscore) was calculated. There were 11 features in the four-phase combined model. The efficiency of the combined model increased significantly compared to each single-phase MRI model. Radscore was an independent predictor of liver fluke infection. It was also significantly different between different expression of CK7/ CK19. Meanwhile, liver fluke infection was associated with CK7/CK19 expression. A cut-off value was set up and all patients were divided into high risk and low risk groups of CK7/CK19 positive expression. Radscore was also an independent predictor of these two biomarkers. Overall survival (OS) and recurrence free survival (RFS) of negative liver fluke infection group were significantly better than the positive group. OS and RFS of negative CK7 and CK19 expression were also better, though not significantly. Positive liver fluke infection and CK19 expression prediction groups harbored significantly worse OS and RFS, survival of positive CK7 expression prediction was unsatisfying as well. A radiomics model was established to predict liver fluke infection among HCC patients. This model could also predict CK7 and CK19 expression. OS and RFS could be foreseen by this model at the same time.

Dual transformation therapy for giant hepatocellular carcinoma: Two case reports and review of literature.

BACKGROUND: In the translational therapy of giant hepatocellular carcinoma (HCC), hepatic arterial infusion chemotherapy (HAIC) combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors (TKI) after laparoscopic portal vein ligation (PVL) is extremely rare. This is a dual conversion therapy that combines surgery and oncology. Here, we report two cases of successful surgical completion after dual conversion therapy. CASE SUMMARY: We report that a 54-year-old man and a 69-year-old woman were diagnosed with primary HCC combined with hepatitis B cirrhosis (case 2 also combined with fatty liver) on physical examination. Due to the insufficient residual liver volume assessed before surgery, laparoscopic right PVL was performed, followed by HAIC combined with anti-PD-1 immunotherapy and TKI. Finally, surgical resection was successfully completed, and pathology confirmed that the tumor was mostly necrotic (90%) in one case, and no live tumor tissue was found in the other case. CONCLUSION: In the process of surgical transformation, our treatment plan takes into account the control and transformation of oncology at the same time, which is expected to provide more opportunities for radical hepatectomy and improve the prognosis of patients with large liver cancer.

Universal cutoff for tumor mutational burden in predicting the efficacy of anti-PD-(L)1 therapy for advanced cancers.

Background: The US Food and Drug Administration (FDA)'s tumor-agnostic approval of pembrolizumab in high tumor mutational burden (TMB-high, i.e., TMB≥10 mut/Mb) cases, based on the data from KEYNOTE-158, has raised considerable concerns among the immuno-oncology community. This study aims to statistically infer the optimal universal cutoff in defining TMB-high that is predictive of the efficacy of anti-PD-(L) 1 therapy in advanced solid tumors. Methods: We integrated MSK-IMPACT TMB data from a public cohort and the objective response rate (ORR) for anti-PD-(L) 1 monotherapy across diverse cancer types in published trials. The optimal TMB cutoff was determined by varying the universal cutoff to define TMB-high across cancer types and examining the cancer-level correlation between objective response rate and the proportion of TMB-high cases. The utility of this cutoff in predicting overall survival (OS) benefits from anti-PD-(L) 1 therapy was then evaluated in a validation cohort of advanced cancers with coupled MSK-IMPACT TMB and OS data. In silico analysis of whole-exome sequencing data from The Cancer Genome Atlas was further employed to assess the generalizability of the identified cutoff among panels comprising several hundred genes. Results: The cancer type-level analysis identified 10 mut/Mb as the optimal cutoff for MSK-IMPACT in defining TMB-high, with the corresponding TMB-high (TMB≥10 mut/Mb) percentage strongly correlated with ORR for PD-(L) 1 blockade across cancer types [correlation coefficient, 0.72 (95% CI, 0.45-0.88)]. This cutoff was also the optimum in defining TMB-high (via MSK-IMPACT) when predicting OS benefits from anti-PD-(L) 1 therapy in the validation cohort. In this cohort, TMB≥10 mut/Mb was associated with significantly improved OS (hazard ratio, 0.58 [95% CI, 0.48-0.71]; p < 0.001). Moreover, in silico analyses revealed excellent agreement of TMB≥10 mut/Mb cases between MSK-IMPACT and the FDA-approved panels and between MSK-IMPACT and various randomly sampled panels. Conclusion: Our study demonstrates that 10 mut/Mb is the optimal, universal cutoff for TMB-high that guides the clinical application of anti-PD-(L) 1 therapy for advanced solid tumors. It also provides rigorous evidence beyond KEYNOTE-158 for the utility of TMB≥10 mut/Mb in predicting the efficacy of PD-(L) 1 blockade in broader settings, which could help to mitigate the challenges in embracing the tumor-agnostic approval of pembrolizumab in TMB-high cases.

Spatial-temporal evolution and peak prediction of embodied carbon emissions in China's interregional trade.

The embodied carbon in inter-regional trade has a vital impact on the allocation of carbon emission reduction obligations and the formulation of carbon emission reduction strategies. Fewer studies have examined the spatial-temporal evolution pattern and peak prediction of embodied carbon emissions in China's inter-regional trade compared with the more numerous results on embodied carbon in international commerce. This paper applies the multi-regional input-output method to estimate the embodied carbon in inter-regional trade resulting from value-added transfer and investigates the spatial and temporal evolution of its patterns. The existence of an environmental Kuznets curve model with embodied carbon emissions as the index of environmental pollution in China is examined, and the time of the inflection point is calculated. The environmental Kuznets curve model is divided into four stages, and a two-dimensional model of economic development and embodied carbon emissions is proposed. The empirical findings indicate that the embodied carbon in China's interregional commerce has an overall rising tendency in the temporal dimension and a distribution characteristic of high in the west and north and low in the east and south in the spatial dimension. The Environmental Kuznets curve, which uses embodied carbon emissions as a measure of environmental pollution, has an inverse U-shaped and the time required to reach the inflection point varies by area. Economic development cannot be cross-stage but can shorten the duration of high carbon emissions. The government should promote the development of differentiated carbon emission reduction policies in each region, construct an inter-regional cooperative carbon emission reduction mechanism, encourage the low-carbon development of inter-regional trade, and realize the internal cycle of China's green economy. This study serves as a guide for the regions to establish scientific and acceptable carbon emission reduction strategies in order to achieve quality interregional trade development.

Synergistic Effects of International Oil Price Fluctuations and Carbon Tax Policies on the Energy-Economy-Environment System in China.

Catalyzed by COVID-19 and the Russia-Ukraine conflict, oil prices fluctuate dramatically on the worldwide market. Both international oil price changes and carbon tax policies have a direct impact on energy costs, thus influencing energy security and emission reduction impacts. Therefore, assessing the interaction effects of international oil price variations and carbon tax policies can assist in resolving the competing challenges of energy security and carbon emission reduction. The impact of international oil price fluctuations on China's energy-economic-environment system under the baseline scenario and carbon taxation scenario is analyzed by constructing a computable general equilibrium model comprising six modules: production, trade, institutions, price, environment, and equilibrium. The findings indicate that, in addition to reducing high-carbon energy consumption and increasing demand for clean electricity, rising international oil prices have a negative effect on real GDP, resulting in lower output in sectors other than construction, and a positive effect on the environmental system by driving carbon emission reductions. In contrast, decreasing international oil prices have the opposite effect. Nevertheless, the impact of rising and decreasing international oil prices is asymmetrical, with the positive shock effect being smaller than the negative. The carbon tax policy can effectively offset the increase in carbon emissions caused by the decline in international oil prices, which is conducive to promoting the development of clean energy, while simultaneously causing an increase in product prices and arousing a contraction in consumer demand, which has a limited negative impact on the macroeconomy.

Caspase-8 inactivation drives autophagy-dependent inflammasome activation in myeloid cells.

Caspase-8 activity controls the switch from cell death to pyroptosis when apoptosis and necroptosis are blocked, yet how caspase-8 inactivation induces inflammasome assembly remains unclear. We show that caspase-8 inhibition via IETD treatment in Toll-like receptor (TLR)-primed Fadd-/-Ripk3-/- myeloid cells promoted interleukin-1ß (IL-1ß) and IL-18 production through inflammasome activation. Caspase-8, caspase-1/11, and functional GSDMD, but not NLRP3 or RIPK1 activity, proved essential for IETD-triggered inflammasome activation. Autophagy became prominent in IETD-treated Fadd-/-Ripk3-/- macrophages, and inhibiting it attenuated IETD-induced cell death and IL-1ß/IL-18 production. In contrast, inhibiting GSDMD or autophagy did not prevent IETD-induced septic shock in Fadd-/-Ripk3-/- mice, implying distinct death processes in other cell types. Cathepsin-B contributes to IETD-mediated inflammasome activation, as its inhibition or down-regulation limited IETD-elicited IL-1ß production. Therefore, the autophagy and cathepsin-B axis represents one of the pathways leading to atypical inflammasome activation when apoptosis and necroptosis are suppressed and capase-8 is inhibited in myeloid cells.

High-salt diet accelerates bone loss accompanied by activation of ion channels related to kidney and bone tissue in ovariectomized rats.

Excessive salt intake can induce a variety of diseases, such as hypertension, cardiovascular disease, kidney disease and so on，it is also one of the factors promoting bone resorption. The mechanism of osteoporosis-induced exacerbations of high salt diet is not well-defined. In this study, we used ovariectomized 6-month-old Sprague Dawley rats to construct a high bone turnover model, and then administrated with high sodium chloride diet (2.0% w/w NaCl, 8.0% w/w NaCl) for 12 weeks to observe the effect of high salt diet on bone metabolism. The results showed that high salt diet could lead to the destruction of bone microstructure, promote the excretion of urinary calcium and phosphorus and accelerate the bone turnover, as well as cause the pathologic structural abnormalities in renal tubular. At the same time, it was accompanied by the up-regulated expression of the epithelial sodium channel (ENaCα), voltage-gated chloride channels (ClC)- 3 and the down-regulated expression of Na-Cl cotransporter (NCC), sodium calcium exchanger (NCX1) in femoral tissue and renal tubules. These findings confirm that high salt diet can destroy the microstructure of bone by increasing bone resorption and affect some ion channels of bone tissue and renal tubule in ovariectomized rats.

[Clinical efficacy of combined therapy in children with stage 4 neuroblastoma]. / 儿童4期神经母细胞瘤联合治疗的临床疗效观察.

OBJECTIVES: To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma. METHODS: A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021. RESULTS: The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years. CONCLUSIONS: Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.

Combination of monoammonium glycyrrhizinate and cysteine hydrochloride protects mice against acetaminophen-induced liver injury via Keap1/Nrf2/ARE pathway.

OBJECTIVES: Acetaminophen (APAP) overdose has been the primary cause of drug-induced liver injury (DILI) in western countries. Monoammonium glycyrrhizinate (MG) is a primary active ingredient from glycyrrhiza. Cysteine hydrochloride (CH) is a component of glutathione (GSH). The study aimed to explore the therapeutical effect of MG-CH against DILI incurred by intragastric APAP. METHODS: Mice were randomized into eight groups: control, APAP, three groups accepted APAP and the combination of MG and CH (15, 30, 60 mg/kg), two groups accepted APAP and MG (40 mg/kg) or CH (20 mg/kg), moreover, one group received MG-CH (60 mg/kg) without APAP. After pretreatment with MG-CH or MG and CH alone for 3 days, mice were administered APAP by oral gavage. The serum and tissue were collected to detect the activities of liver enzymes and evaluate the change of histomorphology and explore the possible mechanism of MG-CH in protecting against DILI. KEY FINDINGS: MG-CH pretreatment remarkably alleviated hepatic injury and decreased the activities of ALT, AST, ALP and LDH. The hepatic ROS and MDA contents were decreased, and the level of GSH and GSH-PX activities was increased in the serum. Furthermore, MG-CH improved the expression of Nrf2, HO-1, GCLM and NQO1 to increase antioxidant ability and induce detoxification. The expression of IL-10 suppressing excessive inflammatory responses was enhanced. CONCLUSION: The study demonstrated that MG-CH had protective effects against DILI induced by APAP and the potential mechanisms were based on inhibiting oxidative stress and activating the Keap1/Nrf2/ARE pathway.

Postharvest quality maintenance of wax apple and guava fruits by use of a fermented broth of an ε-poly-l-lysine-producing Streptomyces strain.

ε-Poly-l-lysine (ε-PL) is a natural antimicrobial polymer with significant inhibitory activity against a broad spectrum of microorganisms, and nowadays used widely as a preservative in the food industry. In the present study, ε-PL broth was obtained from Streptomyces ahygroscopicus GIM8 fermentation in a nutrient-limited liquid medium. The in vitro antifungal activity of the broth against fruit pathogens Penicillium expansum and Colletotrichum gloeosporioides was investigated, and its usage for postharvest storage of two highly perishable fruits wax apple and guava was evaluated. Results showed that ε-PL concentration in the broth reached 0.61 g/L, and the nutrition level of the broth was low. The antifungal activity of ε-PL broth was comparable to that of the aqueous solution of ε-PL under the same concentration. Immersion with the diluted broth (200 mg/L ε-PL) markedly delayed the decline in the quality of postharvest wax apple and guava fruits during storage, and the decay incidences were also greatly decreased as compared to their respective controls (distilled water immersion). A further investigation demonstrated that the ε-PL broth immersion induced an increase in the activity of defense-related enzymes peroxidase and polyphenol oxidase in the two fruits during storage. The present study proved that the fermentation broth of ε-PL could be used as a promising alternative to high purity ε-PL and synthetic fungicides for preserving fruits at postharvest stage.

Clinical implications and molecular mechanisms of Cyclin-dependent kinases 4 for patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) was frequently considered as a kind of malignant tumor with a poor prognosis. Cyclin-dependent kinases (CDK) 4 was considered to be cell-cycle-related CDK gene. In this study, we explored the clinical significance of CDK4 in HCC patients. METHODS: Data of HCC patients were obtained from The Cancer Genome Atlas database (TCGA) and the Gene Expression Omnibus (GEO) database. Kaplan-Meier analysis and Cox regression model were performed to calculate median survival time (MST) and the hazard ration (HR), respectively. The joint-effect analysis and prognostic risk score model were constructed to demonstrate significance of prognosis-related genes. The differential expression of prognostic genes was further validated using reverse transcription-quantitative PCR (RT-qPCR) of 58 pairs of HCC samples. RESULTS: CDK1 and CDK4 were considered prognostic genes in TCGA and GSE14520 cohort. The result of joint-effect model indicated patients in CDK1 and CDK4 low expression groups had a better prognosis in TCGA (adjusted HR = 0.491; adjusted P = 0.003) and GSE14520 cohort (adjusted HR = 0.431; adjusted P = 0.002). Regarding Kaplan-Meier analysis, high expression of CDK1 and CDK4 was related to poor prognosis in both the TCGA (P < 0.001 and = 0.001 for CDK1 and CDK4, respectively) and the GSE14520 cohort (P = 0.006 and = 0.033 for CDK1 and CDK4, respectively). However, only CDK4 (P = 0.042) was validated in RT-qPCR experiment, while CDK1 (P = 0.075) was not. CONCLUSION: HCC patients with high CDK4 expression have poor prognosis, and CDK4 could be a potential candidate diagnostic biomarker for HCC.

Early Death and Survival of Patients With Acute Promyelocytic Leukemia in ATRA Plus Arsenic Era: A Population-Based Study.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

High sodium chloride affects BMP-7 and 1α-hydroxylase levels through NCC and CLC-5 in NRK-52E cells.

A diet high in sodium chloride (NaCl) can affect renal function damage and increase urinary calcium excretion, leading to bone loss. in renal tubules, Na-Cl co-transporter (NCC) and chloride channel 5 (CLC-5) are involved in regulating urinary calcium excretion. In addition, some cytokines, such as Bone morphogenetic protein 7 (BMP-7) and 1α-hydroxylase, are synthesized by renal tubules, which target on bone and play important roles on bone metabolism. However, the specific mechanisms between NaCl and these ion channels or cytokines still need investigations from many aspects. This study, in culture normal rat renal tubular epithelial NRK-52E cells, showed that high concentrations of NaCl significantly inhibited the cell viability and increased the cell apoptosis. High concentration of NaCl reduce bone mineral density (BMD), as demonstrated by the significantly increased mRNA and protein levels of NCC and osteopontin (OPN), but decreased the levels of CLC-5, BMP-7, and 1α-hydroxylase. In addition, we found that ovariectomized (OVX) rats on a high-salt diet for 12 weeks had altered levels of these indices in the renal cortices. Moreover, the BMD in fourth and fifth lumbar vertebra (LV4 and 5) and femurs were significantly decreased and bone microstructure was destroyed of these rats. We also demonstrated that high concentration of NaCl enhanced the inhibition of these cytokines which is beneficial to increase BMD, induced by modulating ion channels NCC and CLC-5. In conclusion, our results indicate that high concentration of NaCl reduce BMD by regulating ion channels NCC and CLC-5.

HIF-2α is indispensable for regulatory T cell function.

Hypoxia-inducible factor 1α (HIF-1α) and HIF-2α are master transcription factors that regulate cellular responses to hypoxia, but the exact function in regulatory T (Treg) cells is controversial. Here, we show that Treg cell development is normal in mice with Foxp3-specific knockout (KO) of HIF-1α or HIF-2α. However, HIF-2α-KO (but not HIF-1α-KO) Treg cells are functionally defective in suppressing effector T cell-induced colitis and inhibiting airway hypersensitivity. HIF-2α-KO Treg cells have enhanced reprogramming into IL-17-secreting cells. We show crosstalk between HIF-2α and HIF-1α, and that HIF-2α represses HIF-1α expression. HIF-1α is upregulated in HIF-2α-KO Treg cells and further deletion of HIF-1α restores the inhibitory function of HIF-2α-KO Treg cells. Mice with Foxp3-conditional KO of HIF-2α are resistant to growth of MC38 colon adenocarcinoma and metastases of B16F10 melanoma. Together, these results indicate that targeting HIF-2α to destabilize Treg cells might be an approach for regulating the functional activity of Treg cells.

Bile in bronchi: A case report.

BACKGROUND: The biliary bronchial fistula is rare and difficult to treat. Here we report a 49-year-old woman diagnosed with biliary bronchial fistula due to cough with yellow-green sputum. CASE PRESENTATION: this is a typical case of the biliary bronchial fistula with typical symptoms. The position of the abscess cavity below the diaphragm could not be catheter drainage. After anti-infection treatment, yellow-green sputum was reduced. Follow-up showed a good prognosis. CONCLUSION: biliary bronchial fistula is rare in the clinic, combined with chest and abdomen infection.

Tumor suppressor death-associated protein kinase 1 inhibits necroptosis by p38 MAPK activation.

Death-associated protein kinase 1 (DAPK1, DAPk, DAPK) is known for its involvement in apoptosis and autophagy-associated cell death. Here, we identified an unexpected function of DAPK1 in suppressing necroptosis. DAPK1-deficiency renders macrophages and dendritic cells susceptible to necroptotic death. We also observed an inhibitory role for DAPK1 in necroptosis in HT-29 cells, since knockdown or knockout of DAPK1 in such cells increased their sensitivity to necroptosis. Increased necroptosis was associated with enhanced formation of the RIPK1-RIPK3-MLKL complex in these DAPK1-deficient cells. We further found that DAPK1-deficiency led to decreased MAPK activated kinase 2 (MK2) activation and reduced RIPK1 S321 phosphorylation, with this latter representing a critical step controlling necrosome formation. Most TNF signaling pathways, including ERK, JNK, and AKT, were not regulated by DAPK. In contrast, DAPK bound p38 MAPK and selectively promoted p38 MAPK activation, resulting in enhanced MK2 phosphorylation. Our results reveal a novel role for DAPK1 in inhibiting necroptosis and illustrate an unexpected selectivity for DAPK1 in promoting p38 MAPK-MK2 activation. Importantly, our study suggests that modulation of necroptosis and p38/MK2-mediated inflammation may be achieved by targeting DAPK1.

Effectiveness associated with different therapies for senile osteoporosis: a network Meta-analysis.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of Chinese herbal medicines for invigorating the kidney (CHMIK) on senile osteoporosis. METHODS: We searched for studies in English-language databases (PubMed, the Cochrane Library, and Web of Science) and Chinese-language databases (China National Knowledge Infrastructure, Wan Fang Data, VIP Chinese periodical service platform, and China Biology Medicine disc from their inception to September 2017. Randomized controlled trials comparing the effectiveness of Traditional Chinese Medicine therapies (alone or in combination) and conventional clinical medicine therapies among older adult patients with osteoporosis were identified. We conducted a network Meta-analysis with a Bayesian hierarchical random-effects model using RStudio software, Version 3.4.1. RESULTS: Forty-three randomized controlled trials assessing the differences between Traditional Chinese Medicine and conventional clinical medicine were identified, including 15 treatments and involving 3316 patients. The results of the network Meta-analysis indicated that alendronate (odds ratio [OR] = 0.20, 95% confidence interval [CI]: 0.047-0.73) and calcium (OR = 0.18, 95% CI: 0.11-0.30) are significantly more effective if combined with oral CHMIK. CHMIK alone is significantly more effective than both alendronate (OR = 0.34, 95% CI: 0.10-1.0) and calcium (OR = 0.13, 95% CI: 0.056-0.28). Moreover, CHMIK + tuina + calcium is more effective than CHMIK + calcium + vitamin D + alendronate (OR = 18.0, 95% CI: 1.1-2.7e + 02). CONCLUSION: The present network Meta-analysis found that alendronate and calcium are more effective if combined with oral CHMIK and that oral CHMIK alone may be more effective than alendronate or calcium. Tuina may have an advantage over oral medicines. Oral CHMIK and calcitonin show the most potential for treating senile osteoporosis.

Oncogene UBE2I enhances cellular invasion, migration and proliferation abilities via autophagy-related pathway resulting in poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a worldwide malignancy with high morbidity and mortality. In this study, ubiquitin conjugating enzyme E2I (UBE2I), a small ubiquitin-like modifier E2 enzyme reportedly expressed in tumors, was examined for its potential effects in HCC. Bioinformatics analysis was performed based on HCCDB, TIMER, and Kaplan-Meier plotter databases to explore the clinical implications in HCC. An siRNA kit was used to downregulate UBE2I, and in vitro experiments-including migration, invasion and proliferation assays-were performed to examine UBE2I expression in HCC. Western blot (WB) was used to determine whether downregulated UBE2I expression influenced the prognosis of HCC via autophagy pathways. Finally, RNA-sequencing was performed to explore candidate molecular mechanisms underlying the effect of UBE2I. Bioinformatics analysis including stratification by alcohol ingestion and hepatitis status in HCC showed that highly expressed UBE2I was not only correlated with poor prognosis, but was also associated with immune infiltrates. In vitro experiments showed that high expression of UBE2I was associated with increased migration, invasion and proliferation of HCC cells. WB results indicated that downregulated expression of UBE2I was associated with higher levels of autophagy-related proteins including LC3A/B, Beclin-1 and ATG16L1. Moreover, RNA-sequencing results suggested that UBE2I was involved in hepatocarcinogenesis, non-alcohol fatty liver disease, steatohepatitis, liver fibrosis, inflammation, hepatoblastoma, tumor angiogenesis, type 2 mellitus diabetes, biliary tract disease and other diseases. We conclude that oncogene UBE2I is associated with poor prognosis of HCC via autophagy pathways and may be involved in hepatocarcinogenesis, tumor angiogenesis, non-alcohol fatty liver disease and inflammation.

MiR-210-3p inhibits osteogenic differentiation and promotes adipogenic differentiation correlated with Wnt signaling in ERα-deficient rBMSCs.

MicroRNAs (miRNAs) regulate activities in living organisms through various signaling pathways and play important roles in the development and progression of osteoporosis. The balance between osteogenic and adipogenic differentiation of rBMSCs is closely related to the occurrence of osteoporosis. ERα regulates bone metabolism in various tissues. However, the correlation among ERα, miRNAs, and the differentiation of rBMSCs is still unclear. In this study, we used lentivirus transfection into rBMSCs to construct an ERα-deficient model, analyzed the differences in expressed miRNAs between control and ERα-deficient rBMSCs. The results revealed that the expression of 25 miRNAs were upregulated, 164 miRNAs were downregulated, and some of the regulated miRNAs such as miR-210-3p and miR-214-3p were related to osteogenic or adipogenic differentiation, as well as to particular signaling pathways. Next, we overexpressed miR-210-3p to evaluate its effects on the osteogenic and adipogenic differentiation of rBMSCs, and identified the relationship among miR-210-3p, Wnt signaling pathway, and the differentiation of rBMSCs. The results indicated that ERα-deficient inhibited osteogenic differentiation, promoted adipogenic differentiation, and regulated the expression of some miRNAs. Meanwhile, overexpression of miR-210-3p promoted osteogenic differentiation and inhibited adipogenic differentiation of rBMSCs, processes likely to be related to the Wnt signaling pathway. In conclusion, we identified a group of upregulated and downregulated miRNAs in ERα-deficient rBMSCs that might play a vital role in regulating osteogenic or adipogenic differentiation. One of these, miR-210-3p, inhibited osteogenic differentiation and promoted adipogenic differentiation correlated with the Wnt signaling pathway in ERα-deficient rBMSCs, providing new insight into the regulation of bone metabolism.