Localization of Ectopic Hyperparathyroidism: Ultrasound Versus 99mTc-sestamibi, 4-Dimensional Computed Tomography, and 11C-choline Positron Emission Tomography/Computed Tomography.

OBJECTIVE: To investigate the usefulness of ultrasound (US) for the localization of ectopic hyperparathyroidism and compare it with 99mTc-sestamibi (99mTc-MIBI), 4-dimensional computed tomography (4D-CT), and 11C-choline positron emission tomography/ computed tomography (PET/CT). METHODS: Of the 527 patients with surgically confirmed primary hyperparathyroidism, 79 patients with ectopic hyperparathyroidism were enrolled. The diagnostic performance of US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT was calculated, and the factors affecting the sensitivity of US and 99mTc-MIBI were analyzed. RESULTS: Eighty-three ectopic parathyroid lesions were found in 79 patients. The sensitivity was 75.9%, 81.7%, 95.1%, 83.3%, and 100% for US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT, respectively. The difference in sensitivity among these different modalities did not achieve statistical significance (P > .05). The US sensitivity was significantly higher for ectopic lesions in the neck region than for those in the anterior mediastinum/chest wall (85.9% vs. 42.1%, P < .001). The 99mTc-MIBI and 4D-CT sensitivity was not significantly different between these two groups (84.1% vs. 94.6%, P = .193 and 81.3% vs. 85.7%, P = 1). The 11C-choline PET/CT sensitivity was 100% in both groups. CONCLUSIONS: US is a valuable tool for the localization of ectopic hyperparathyroidism, especially for ectopic lesions in the neck region.

Evaluation of chemotherapy and radiotherapy in the adjuvant management of uterine carcinosarcoma: a population-based analysis.

PURPOSE: To evaluate the effects of adjuvant chemotherapy (CT) and radiotherapy (RT) on the survival of uterine carcinosarcoma (UCS) patients. METHODS: We analyzed 3207 patients with uterine carcinosarcoma without distant metastasis after surgery from 2004 to 2015 by utilizing data from the Surveillance, Epidemiology, and End Results database. Generally, cancer-specific survival (CSS) and overall survival (OS) outcomes were analyzed by Kaplan-Meier and Cox proportional hazards regression models. Further subgroup survival analysis was performed for those receiving RT and chemoradiotherapy (CRT). RESULTS: In general, both univariate and multivariate analyses showed that age, race, marital status, stage, lymph node metastasis, lymphadenectomy (LND), RT, and chemotherapy (CT) were associated with improved CSS and OS (P < 0.05). Further subgroup analysis showed that CRT exhibited a survival advantage over RT or CT alone in different groups. Various RT modalities, including brachytherapy (BT), external radiotherapy (EBRT), and EBRT + BT, were correlated with improved survival for patients aged 60-69 years with stage III-IV disease and lymph node metastasis. Patients with stage I-II disease aged > 70 years seemed to gain survival benefits from brachytherapy (BT) alone. BT with or without external radiotherapy was associated with improved survival for those who did not undergo lymphadenectomy. CONCLUSION: For UCS without distant metastasis after surgery, CRT should be considered. Regarding RT, BT alone is efficient in improving survival, especially for patients with stage I-II disease aged > 70 years old. EBRT alone does not show results in survival improvement for patients who did not undergo LND and those with lymph node metastasis. However, considering the limitation of SEER database, further studies with more large sample size and strict study design are needed to confirm it.

Association of an IGHV3-66 gene variant with Kawasaki disease.

In a meta-analysis of three GWAS for susceptibility to Kawasaki disease (KD) conducted in Japan, Korea, and Taiwan and follow-up studies with a total of 11,265 subjects (3428 cases and 7837 controls), a significantly associated SNV in the immunoglobulin heavy variable gene (IGHV) cluster in 14q33.32 was identified (rs4774175; OR = 1.20, P = 6.0 × 10-9). Investigation of nonsynonymous SNVs of the IGHV cluster in 9335 Japanese subjects identified the C allele of rs6423677, located in IGHV3-66, as the most significant reproducible association (OR = 1.25, P = 6.8 × 10-10 in 3603 cases and 5731 controls). We observed highly skewed allelic usage of IGHV3-66, wherein the rs6423677 A allele was nearly abolished in the transcripts in peripheral blood mononuclear cells of both KD patients and healthy adults. Association of the high-expression allele with KD strongly indicates some active roles of B-cells or endogenous immunoglobulins in the disease pathogenesis. Considering that significant association of SNVs in the IGHV region with disease susceptibility was previously known only for rheumatic heart disease (RHD), a complication of acute rheumatic fever (ARF), these observations suggest that common B-cell related mechanisms may mediate the symptomology of KD and ARF as well as RHD.

The Selection of Treatment Modality for Breast Ductal Carcinoma In Situ: Experience From a Single Institution.

PURPOSE: Although breast conservation surgery(BCS) followed by adjuvant radiotherapy is now the mainstream treatment method for breast ductal carcinoma in situ(DCIS), mastectomy is still performed in some patients who refuse to undergo radiation. However, the most effective treatment method for these patients is still unknown. In the current study, we aimed to compare the survival rates between mastectomy and BCS plus adjuvant radiotherapy in patients with DCIS. MATERIALS AND METHODS: We performed a retrospective study of 333 patients with DCIS from May 2004 to December 2016. There were 209 patents who were treated with BCS and adjuvant radiotherapy, while the remaining of 124 patients underwent mastectomy. The disease-free survival (DFS) and local recurrence-free survival(LRFS) rates were compared between the 2 treatment groups. Cox proportional hazards regression was performed to explore factors associated with DFS and LRFS. RESULTS: The 10-year local recurrence(LR) rates in the mastectomy and BCS plus adjuvant radiotherapy groups were 2.6% and 7.5%, respectively. There was no difference in the LR rate between the 2 groups. Furthermore the DFS rate was also similar between the mastectomy and BCS plus adjuvant radiotherapy groups. Based on the multivariable analysis, age and tumor grade were significantly correlated with the LRFS and DFS rates. In the subgroup analysis based on the factors of age and tumor grade, patients with a tumor grade of III who underwent mastectomy had better LRFS and DFS rates compared to those who received BCS plus radiotherapy. CONCLUSION: In patients with DCIS, the long-term efficacy was similar between mastectomy and BCS followed by adjuvant radiotherapy. However, in the subgroup of patients with grade III tumors, mastectomy seems to offer a better LRFS and DFS than BCS plus radiotherapy.

Association between ambient air pollution and hyperuricemia in traffic police officers in China: a cohort study.

To evaluate the association between ambient air pollution and hyperuricemia, we prospectively followed 1748 traffic police officers without hyperuricemia at baseline (2009-2014) from 11 districts in Guangzhou, China. We calculated six-year average PM10, SO2 and NO2 concentrations using data collected from air monitoring stations. The hazard ratios for hyperuricemia per 10 µg/m3 increase in air pollutants were 1.46 (95% CI: 1.28-1.68) for PM10, 1.23 (95% CI: 1.00-1.51) for SO2, and 1.43 (95% CI: 1.26-1.61) for NO2. We also identified changes in the ratio of serum uric acid to serum creatinine concentrations (ua/cre) per 10 µg/m3 increase in air pollutants as 11.54% (95% CI: 8.14%-14.93%) higher for PM10, 5.09% (95% CI: 2.76%-7.42%) higher for SO2, and 5.13% (95% CI: 2.35%-7.92%) higher for NO2, respectively. Long-term exposure to ambient air pollution was associated with a higher incidence of hyperuricemia and an increase in ua/cre among traffic police officers.

Microarray analysis of altered long non-coding RNA expression profile in liver cancer cells treated by ginsenoside Rh2.

Microarray expression profiles of lncRNAs and mRNAs were investigated in HepG2 cells treated with 20 µg/ml ginsenoside Rh2 as well as in ginsenoside Rh2-untreated cells. Microarray analysis showed 618 upregulated lncRNAs and 161 downregulated lncRNAs in HepG2 cells treated with ginsenoside Rh2 compared with the control group. Moreover, three differentially expressed lncRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). This may be beneficial to patients as an anti-cancer treatment and potentially provide novel targets for HCC (hepatocellular carcinoma) therapy.

The Selection of Time Interval Between Surgery and Adjuvant Therapy in Early Stage Cervical Cancer.

OBJECTIVES: The optimal interval between surgery and adjuvant treatment has not yet been found in cervical cancer. And whether patients with different FIGO stage should choose different interval is unknown. The purpose of this study was to evaluate whether interval has a different effect on oncologic outcome for patients with different tumor stages. METHODS: We performed a retrospective study of 226 cervical cancer patients who were treated by surgery and adjuvant therapy from May 2005 to August 2015. All patients were divided into 2 groups according to the interval of 5 weeks. Overall survival (OS) and disease-free survival (DFS) were compared between patients with interval shorter and longer than 5 weeks in the whole group and subgroups. Recurrence patterns were also analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival and distant metastasis-free survival for patients with stage IB2-IIA. RESULTS: For patients with stage IA2-IB1, the 5-year OS and DFS were similar between groups of short and long interval with also the comparable results of local and distant failure. For patients with IB2-IIA, both the OS and DFS in the short-interval group were higher than that in the long-interval group. Besides, the rates of local recurrence were found higher in the group of long interval compared with short interval. Multivariable analysis indicated that time interval was an independent predictor of DFS and local recurrence-free survival for patients with stage IB2-IIA. CONCLUSIONS: In cervical cancer patients, time interval between surgery and adjuvant therapy may have different effects on the prognosis in different FIGO stages.

CXCL10/IP-10 is a biomarker and mediator for Kawasaki disease.

RATIONALE: Kawasaki disease (KD), an acute febrile vasculitis, is the most common cause of acquired heart disease in childhood; however, diagnosing KD can be difficult. OBJECTIVE: To identify unique proteomic biomarkers that can be used to facilitate earlier diagnosis of KD. METHODS AND RESULTS: We enrolled 214 children with fever and clinical features suggestive of KD. Of those, only 100 were diagnosed with KD. Their plasma samples were globally analyzed for cytokines, chemokines, and cell adhesion molecules using an unbiased, large-scale, quantitative protein array. This study was conducted in 3 stages: discovery, replication, and blinded validation. During the discovery phase (n [KD]=37; n [control]=20), the expression of interleukin-17F, sCD40L, E-selectin, CCL23 (myeloid progenitor inhibitory factor 1), and CXCL10 (IFN-γ-inducible protein 10 [IP-10]) were upregulated during the acute phase in patients with KD when compared with that in the controls. A notable increase was observed in the IP-10 levels (KD, 3037 ± 226.7 pg/mL; control, 672 ± 130.4 pg/mL; P=4.1 × 10(-11)). Receiver-operating characteristic analysis of the combined discovery and replication data (n [KD]=77; n [control]=77) showed that the IP-10 level had high area under the curve values (0.94 [95% confidence interval, 0.9055-0.9778]; sensitivity, 100%; and specificity, 77%). With 1318 pg/mL as the optimal cutoff, the blinded validation study confirmed that the IP-10 levels were a good predictor of KD. With intravenous immunoglobulin treatment, the IP-10 levels returned to normal. The downstream receptor of IP-10, CXCR3, was activated in the T cells of patients with acute KD. CONCLUSIONS: IP-10 may be used as a biomarker to facilitate KD diagnosis, and it may provide clues about the pathogenesis of KD.

Human cytomegalovirus UL49 encodes an early, virion-associated protein essential for virus growth in human foreskin fibroblasts.

Despite recent results of deletion experiments showing that open reading frame (ORF) UL49 of human cytomegalovirus (HCMV) is essential, the expression, function and functional location of its encoded protein remain unknown. We generated an antibody specific for pUL49 to investigate the protein product encoded by the UL49 ORF and identified its function in HCMV-infected host foreskin fibroblasts. A bacterial artificial chromosome (BAC) of HCMV strain Towne (pRV-Towne) and the UL49-deleted mutant pRV-delUL49Towne were used to observe virus growth by plaque assay. Using a UL49-protein-binding antibody, we located pUL49 in the fibroblast cytoplasm. pUL49 exhibited expression kinetics resembling those of the class ß-2 proteins and was detected in the virion tegument. Following deletion of UL49 ORF, the virus failed to replicate, but it could be recovered by addition of pUL49 from pCDNA3.1 (+)-UL49. Our findings indicate that UL49 ORF is essential for HCMV replication in host foreskin fibroblasts.

Pyrimidinedione-mediated selective histone deacetylase 6 inhibitors with antitumor activity in colorectal cancer HCT116 cells.

We synthesized a series of pyrimidinedione derivatives and evaluated their activities. The results indicate that compound 6, 4-[5-fluoro-2,6-dioxo-3-(tetrahydro-furan-2-yl)-3,6-dihydro-2H-pyrimidin-1-ylmethyl]-N-hydroxy-benzamide, exhibits potent antiproliferative activity, apoptosis induction with cleavage of caspase and PARP, and enhanced tendency to inhibit HDAC6 (IC50 = 12.4 nM) activity over HDAC1 (IC50 = 1710 nM) and HDAC2 (IC50 = 5500 nM). Compound 6 also inhibits tumor growth and is less toxic than parent 4 in vivo. These data provide compelling evidence that compound 6 is a potential antitumor compound with HDAC6 targeted inhibitory activity and may be tested for preclinical investigation for cancer treatment.

Nab-paclitaxel, cisplatin, and capecitabine versus cisplatin and gemcitabine as first line chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma: randomised phase 3 clinical trial.

OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.

Pseudorabies virus variant in Bartha-K61-vaccinated pigs, China, 2012.

The widely used pseudorabies virus (PRV) Bartha-K61 vaccine has played a key role in the eradication of PRV. Since late 2011, however, a disease characterized by neurologic symptoms and a high number of deaths among newborn piglets has occurred among Bartha-K61-vaccinated pigs on many farms in China. Clinical samples from pigs on 15 farms in 6 provinces were examined. The PRV gE gene was detectable by PCR in all samples, and sequence analysis of the gE gene showed that all isolates belonged to a relatively independent cluster and contained 2 amino acid insertions. A PRV (named HeN1) was isolated and caused transitional fever in pigs. In protection assays, Bartha-K61 vaccine provided 100% protection against lethal challenge with SC (a classical PRV) but only 50% protection against 4 challenges with strain HeN1. The findings suggest that Bartha-K61 vaccine does not provide effective protection against PRV HeN1 infection.

1-arylsulfonyl-5-(N-hydroxyacrylamide)indolines histone deacetylase inhibitors are potent cytokine release suppressors.

A series of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indolines (7-15) has been developed; the compounds exhibited potent histone deacetylase (HDAC) inhibitory activities. Notably, almost all of this series exhibited better HDAC-inhibitory and antiproliferative activities than 3-(1-benzenesulfonyl-1H-indol-5-yl)-N-hydroxyacrylamide (6), as reported in a previous study. Among these compounds, 3-[1-(4-methoxybenzenesulfonyl)-2,3-dihydro-1H-indol-5-yl]-N-hydroxyacrylamide (9) showed a two- to tenfold increase in activity compared to SAHA (1) in the suppression of lipopolysaccharide-induced cytokine production. Compound 9 also caused a marked reduction in carrageenan-induced acute inflammation in a rat model. Taken together, these data indicated that 1-arylsulfonyl-5-(N-hydroxyacrylamide)indolines HDAC inhibitors exhibit potent anti-inflammatory activity.

A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese.

To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54x10(-10); odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36-1.82), and serine racemase (SRR) (P = 3.06x10(-9); OR = 1.28; 95% CI = 1.18-1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10); OR = 1.29, 95% CI = 1.19-1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations.

[Association of vitamin D receptor gene haplotypes and genotype combinations with susceptibility to occupational elevated blood lead].

OBJECTIVE: To investigate the association of the haplotypes and genotype combinations of vitamin D receptor (VDR) BsmI (rs1544410), Tru9I (rs757343), ApaI (rs7975232), and TaqI (rs731236) with the susceptibility to elevated blood lead in Chinese Han population. METHODS: According to Diagnostic Criteria of Occupational Chronic Lead Poisoning (GBZ 37-2002) and Occupational Exposure Limits for Hazardous Agents in the Workplace Part 1: Chemical Hazardous Agents (GBZ 2.1-2007), the workers were divided into high-exposure group (lead dust ≥ 0.05 mg/m(3), lead fume ≥ 0.03 mg/m(3)) and low-exposure group based on the concentrations of lead fume and lead dust in the workplace. The high-exposure group was further divided into normal-blood lead subgroup and high-blood lead subgroup. Fasting peripheral venous blood (5 ml) was collected using a heparin tube; genomic DNA was extracted from the peripheral blood cells with a Qiagen kit; single nucleotide polymorphisms were detected by allelic discrimination assay using TaqMan probes (carrying fluorescent dyes); haplotypes were analyzed and compared by Haploview. RESULTS: VDR BsmI, Tru9I, ApaI, and TaqI were in Hardy-Weinberg equilibrium between the normal-blood lead subgroup and high-blood lead subgroup (P > 0.05). Compared with haplotype CCCA which had the highest distribution frequency, haplotypes CCAA and CTCA were the high-risk factors for elevated blood lead (OR = 1.814, 95%CI = 1.055 ∼ 3.119; OR = 1.919, 95%CI = 1.040 ∼ 3.540). Compared with genotype combination CC + CC + CC + AA which had the highest distribution frequency, genotype combination CC + CC + AC + AA was the high-risk factor for elevated blood lead (OR = 2.800, 95%CI = 1.282 ∼ 6.116). CONCLUSION: As for VDR BsmI, Tru9I, ApaI, and TaqI, haplotypes CCAA and CTCA and genotype combination CC + CC + AC + AA are associated with the susceptibility to elevated blood lead.

[Analysis of influential factors for job burnout among managers in a joint venture in Guangzhou, China].

OBJECTIVE: To investigate the influential factors for job burnout among the managerial staff in a Sino-Japanese joint venture automobile manufacturer in Guangzhou, China. METHODS: A total of 288 managers in a Sino-Japanese joint venture automobile manufacturer were surveyed using the Occupational Stress Indicator, Maslach Burnout Inventory (MBI), Eysenck Personality Questionnaire, Simplified Coping Style Questionnaire, and Social Support Rating Scale. RESULTS: On the depersonalization dimension, the male managers had significantly higher scores than the female managers. The scores of emotion exhaustion and depersonalization of MBI showed significant differences among the managers with different levels of occupational stress. The path analysis showed that occupational stress, neuroticism, and psychoticism had negative effects on emotion exhaustion, while job satisfaction and utilization of social support had direct positive effects on emotion exhaustion. Occupational stress, psychoticism, and passive coping style had direct negative effects on depersonalization, while job satisfaction, objective support, and utilization of social support had positive effects on depersonalization. Job satisfaction and active coping style had positive effects on sense of personal accomplishment, while passive coping style had a negative effect on sense of personal accomplishment. Personality exerted its effect on social support through coping style and thus on job satisfaction and job burnout. CONCLUSION: Male managers have a greater propensity to depersonalization than their female counterparts. High occupational stress is a risk factor for job burnout. Personality, social support, and coping style are influential factors for job burnout.

[Investigation of screening methods for identifying population susceptible to noise-induced hearing loss].

OBJECTIVE: To investigate the screening methods for identifying the populations susceptible and resistant to noise-induced hearing loss (NIHL) and to provide a reference for future research. METHODS: Workers who were exposed to 75 ∼ 120 dB noise in enterprises were included in the study. Field investigation of occupational health was conducted; workers' basic information and data on hearing threshold levels were collected. Paired chi-square test was used to compare each two of three screening methods, which were used at home and abroad to identify noise-susceptible and noise-sensitive populations, in terms of noise exposure level, general information, and noise-induced hearing threshold shift. RESULTS: There were no significant differences in the noise exposure level, basic information, and left and right ears' hearing threshold levels of noise-susceptible and noise-sensitive populations between each two of the three screening methods (P > 0.05), according to the paired chi-square test. However, high-frequency hearing threshold had statistically significant difference among the three methods. As a whole, methods B and C were superior to method A. CONCLUSION: The workers in China are younger than before, with more awareness of self-protection, and individual protection is enhanced in them. Currently, method B is more suitable for screening out the population susceptible to NIHL in China.

An updated patent review of histone deacetylase (HDAC) inhibitors in cancer (2020 - present).

INTRODUCTION: Histone deacetylase (HDAC) inhibitors have been considered as an attractive strategy to reverse aberrant epigenetic changes associated with cancer treatments. The use of HDAC inhibitors in various cancer types has continued to develop for decades, bringing several novel HDAC inhibitors successfully into clinical trials. The combination use of HDAC inhibitors with other agents have also been developed and have demonstrated superior efficacy compared to that of monotherapy in recent studies. Hence, development of new anticancer treatment and therapeutic regimen is necessary. AREAS COVERED: This review summarizes a comprehensive review of the patent literature from 2020 to 2022 including HDAC inhibitors and their use as anticancer agents (searched from European Patent Office, 2020-2022). The approved and developing HDAC inhibitors are described. It also provides perspectives on the challenges and future opportunities. EXPERT OPINION: Although hundreds of clinical trials of HDAC inhibitors are still going on, the application for HDAC inhibitors has been limited at present . Not only in the anticancer treatment, but also non-oncology disease therapies are being investigated eagerly. Recently, applications of HDAC inhibitors in non-oncology diseases have also been revealed and proceeded to clinical trials. New indications for HDAC inhibitors are needed urgently in the future.

Uncovering the key pharmacodynamic material basis and possible molecular mechanism of extract of Epimedium against liver cancer through a comprehensive investigation.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver cancer is a worldwide malignant tumor, and currently lacks effective treatments. Clinical studies have shown that epimedium (YYH) has therapeutic effects on liver cancer, and some of its prenylflavonoids have demonstrated anti-liver cancer activity through multiple mechanisms. However, there is still a need for systematic research to uncover the key pharmacodynamic material basis and mechanism of YYH. AIM OF THE STUDY: This study aimed to screen the anti-cancer material basis of YYH via integrating spectrum-effect analysis with serum pharmacochemistry, and explore the multi-target mechanisms of YYH against liver cancer by combining network pharmacology with metabolomics. MATERIALS AND METHODS: The anti-cancer effect of the extract of YYH (E-YYH) was first evaluated in mice with xenotransplantation H22 tumor cells burden and cultured hepatic cells. Then, the interaction between E-YYH compounds and the cytotoxic effects was revealed through spectrum-effect relationship analysis. And the cytotoxic effects of screened compounds were verified in hepatic cells. Next, UHPLC-Q-TOF-MS/MS was employed to identify the absorbed components of E-YYH in rat plasma to distinguish anti-cancer components. Subsequently, network pharmacology based on anti-cancer materials and metabolomics were used to discover the potential anti-tumor mechanisms of YYH. Key targets and biomarkers were identified and pathway enrichment analysis was performed. RESULTS: The anti-cancer effect of E-YYH was verified through in vitro and in vivo experiments. Six anti-cancer compounds in plasma (icariin, baohuoside Ⅰ, epimedin C, 2″-O-rhamnosyl icariside Ⅱ, epimedin B and sagittatoside B) were screened out by spectrum-effect analysis. Forty-five liver-cancer-related targets were connected with these compounds. Among these targets, PTGS2, TNF, NOS3 and PPARG were considered to be the potential key targets preliminarily verified by molecular docking. Meanwhile, PI3K/AKT signaling pathway and arachidonic acid metabolism were found to be associated with E-YYH's efficacy in network pharmacology and metabolomics analysis. CONCLUSIONS: Our research revealed the characteristics of multi-component, multi-target and multi-pathway mechanism of E-YYH. This study also provided an experimental basis and scientific evidence for the clinical application and rational development of YYH.

[Whole brain radiation therapy plus temozolomide in the treatment of brain metastases from non small cell lung cancer: a meta-analysis].

OBJECTIVE: To explore the efficacy and safety of whole brain radiation therapy (WBRT) plus temozolomide (TMZ) versus WBRT alone in the treatment of brain metastases from non-small cell lung cancer (NSCLC) through a meta-analysis. METHODS: All previously published and some unpublished studies were comprehensively searched from the databases of MEDLINE, EMBASE, Cochrane Library and CBM, etc. The meta-analysis included all randomized controlled trials (RCTs) to compare WBRT plus TMZ with WBRT alone in treatment of brain metastases from NSCLC. The primary meta-analysis was based upon objective remission (OR) and toxicity and the second overall survival (OS). RESULTS: Four RCTs identified by two reviewers were included. There was significant improvement for the WBRT + TMZ group in OR rate (RR = 1.55, P = 0.003); but without significant improvement in OS (P = 0.69). Meanwhile, WHO grade III/IV hematologic toxicity of myelosuppression increased in the WBRT + TMZ group (RR = 2.47, P = 0.008), but without significant difference in gastrointestinal toxicity (P = 0.14). CONCLUSIONS: For the treatment of brain metastases from NSCLC, the combined therapy of WBRT plus TMZ improves OR, but without significant improvement in OS. And the incidence of myelosuppression is elevated. Future large-scale, high-quality and prospective phase III RCTs are needed to confirm the clinical efficacy and safety of WBRT plus TMZ.