Three new cadinene-type sesquiterpenoids from the aerial parts of Ageratina adenophora.

Three new cadinene sesquiterpenoids 1-3, were isolated from the aerial sections of Ageratina adenophora using various chromatographic techniques. Their structures were characterised by comprehensive spectroscopic investigations (including 1D, 2D-NMR and HRMS), and single crystal X-ray diffraction. The cytotoxic activity of new compounds 1-3 were evaluated by testing in vitro tumour growth inhibitory rate against five human tumour cell lines, HL-60, A-549, SMMC-7721, MDA-MB-231, and SW480.

The risk factors for miscarriage of viable intrauterine pregnancies in patients with heterotopic pregnancy after surgical intervention.

To summarize the clinical characteristics and explore the risk factors for miscarriage of a viable intrauterine pregnancy following surgical intervention in patients with heterotopic pregnancy (HP). A total of 106 women diagnosed with HP that underwent surgical intervention in the Women's Hospital School of Medicine Zhejiang University between January 2014 and December 2021 were included in this retrospective study. They were divided into a miscarriage group (n = 13) and an ongoing pregnancy group (n = 93) according to the outcomes of the HP within 2 weeks after surgery. Data regarding clinical characteristics, surgical conditions, postoperative recovery, and complications were collected and compared between the groups. Logistic multivariate analysis was performed to explore the risk factors for miscarriage in patients with HP within 2 weeks of surgical intervention. Among the 106 women with HP, 80 had tubal HP, 8 had cornual HP, and 18 had interstitial HP. Eighty-seven (82.1%) patients developed clinical symptoms that manifested primarily as abnormal vaginal bleeding and/or abdominal pain, whereas 19 (17.9%) patients had no clinical symptoms. The mean gestational age on the day of surgery was 7.2 weeks (inter-quartile range, 6.4-8.3). The miscarriage rate within 2 weeks of surgical intervention was 12.3% in patients with HP. Compared to the ongoing pregnancy group, the miscarriage group had a higher body mass index, earlier gestational age at treatment, and higher volume of hemoperitoneum (P < .05 for all). Logistic multivariate analysis indicated that the women with a hemoperitoneum volume > 200 mL had significantly higher risk of miscarriage after adjusting covariates [OR (odds ratio) = 5.285, 95% CI (confidence interval) (1.152-24.238), P < .05]. Hemoperitoneum volume was independently associated with miscarriage of viable intrauterine pregnancies in patients with HP within 2 weeks of surgical intervention.

An Analysis of Environment-, Individual-, and Tumor-Related Factors Impacting Hypovitaminosis D in Patients with Malignant Tumors.

Vitamin D (VD) plays a regulatory role in tumor occurrence and development, although the factors influencing serum 25-hydroxyvitamin D3 (25(OH)D3) levels in patients with cancer have not been studied. Therefore, we aimed to evaluate circulating levels of 25(OH)D3 and factors influencing the VD status in patients with malignant tumors. Adult patients with malignant tumors who had undergone assessments of serum 25(OH)D3 at Beijing Cancer Hospital from January 2019 to July 2022 were included. A multiple logistic regression model was applied to explore the associations of patient characteristics, environment, and disease characteristics with 25(OH)D3 levels. Among the 1,076 included patients, the median 25(OH)D3 serum concentration was 16.25 ng/mL. VD deficiency and the combined VD insufficiency and sufficiency were observed in 811 (75.37%) and 265 (24.63%) patients, respectively. Latitude, season, sex, body mass index, and type of cancer were associated with VD concentration/status in patients with malignant tumors. 25(OH)D3 concentrations were significantly higher in patients with thyroid cancer and significantly lower in patients receiving tumor-related treatment than in untreated patients. Surprisingly, we observed 25(OH)D3 serum concentration was lower in patients receiving nutritional supplementation than in those receiving no nutritional supplements. Patients with malignant tumors are at high risk of VD deficiency.

Analysis on the Effect of Radiofrequency Ablation and Electrocautery in the Treatment of Vaginal Intraepithelial Neoplasia.

Objective: This research intends to investigate the clinical efficacy of radiofrequency ablation and electrocautery in treating grade I or II vaginal intraepithelial neoplasia (VaIN). Methods: This is a single-center retrospective study, which collected the clinical data of 100 patients with VaIN diagnosed by colposcopy and pathological biopsy in the Gynecology and Cervical Center of Xiangzhu Branch of the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2020 and June 2021. Patients were divided into the study group (radiofrequency ablation treatment) and the control group (electrocautery) according to differences in treatment approaches. 6- and 12-month follow-ups were performed on all patients. Gynecological examination results, liquid-based thin-layer cytology (TCT), negative conversion of human papillomavirus (HPV), curative effects, and prognosis were recorded. Results: All patients completed regular follow-ups that lasted for 6 and 12 months. The 6- and 12-month cure rates of the study group were 76.0% and 92.0%, respectively, and the data in the control group were 70.0% and 82.0%, respectively. In terms of the 6- and 12-month negative conversion rates of HPV, the data in the study group were 68.0% and 78.0%, versus 60% and 68% in the control group, respectively. The lesion duration rate showed no statistical significance between the study group (8.0%) and the control group (P > 0.05). The analysis of postoperative follow-up complications revealed that the study group had a statistically lower overall incidence of vaginal bleeding, excessive vaginal discharge, vaginal burning sensation, and decreased vaginal elasticity than the control group (8.0% vs. 24.0% P < 0.05). Conclusion: Both radiofrequency ablation and electrocautery have obvious clinical effects in patients with grade I or II VaIN, but the former contributed to fewer operative complications and a good prognosis, which deserves clinical promotion.

Prognostic role of multiple abnormal genes in non-small-cell lung cancer.

BACKGROUND: Non-small-cell lung cancer (NSCLC) has the highest morbidity and mortality rates among all malignant tumor types. Although therapies targeting the mutated genes such as KRAS have been used in the clinic for many years, the prognosis remains poor. Therefore, it is necessary to further study the aberrant expression or mutation of non-target genes affecting the survival and prognosis. AIM: To explore the impact of simultaneous abnormalities of multiple genes on the prognosis and survival of patients. METHODS: We used R packages to analyze gene expression data and clinical data downloaded from The Cancer Genome Atlas (TCGA) database. We also collected samples from 85 NSCLC patients from the First People's Hospital of Jingzhou City and retrospectively followed the patients. Multivariate Cox regression analysis and survival analysis were performed. RESULTS: Analysis of gene expression data from TCGA revealed that the overexpression of the following single genes affected overall survival: TP53 (P = 0.79), PTEN (P = 0.94), RB1 (P = 0.49), CTNNB1 (P = 0.24), STK11 (P = 0.32), and PIK3CA (P = 0.013). However, the probability of multiple genes (TP53, PTEN, RB1, and STK11) affecting survival was 0.025. Retrospective analysis of clinical data revealed that sex (hazard ratio [HR] = 1.29; [95%CI: 0.64-2.62]), age (HR = 1.05; [95%CI: 1.02-1.07]), smoking status (HR = 2.26; [95%CI: 1.16-4.39]), tumor histology (HR = 0.58; [95%CI: 0.30-1.11]), cancer stage (HR = 16.63; [95%CI: 4.8-57.63]), epidermal growth factor receptor (EGFR) mutation (HR = 1.82; [95%CI: 1.05-3.16]), abundance (HR = 4.95; [95%CI: 0.78-31.36]), and treatment with tyrosine kinase inhibitors (TKIs) (HR = 0.58; [95%CI: 0.43-0.78]) affected patient survival. Co-occurring mutations of TP53, PTEN, RB1, and STK11 did not significantly affect the overall survival of patients receiving chemotherapy (P = 0.96) but significantly affected the overall survival of patients receiving TKIs (P = 0.045). CONCLUSION: Co-occurring mutation or overexpression of different genes has different effects on the overall survival and prognosis of NSCLC patients. Combined with TKI treatment, the co-occurring mutation of some genes may have a synergistic effect on the survival and prognosis of NSCLC patients.

Systematic review and meta-analysis of the predictive power of MTHFR polymorphisms for pemetrexed drug efficacy and toxicity in non-small cell lung cancer patients.

We conducted a meta-analysis to determine if MTHFR polymorphisms are effective biomarkers for non-small cell lung cancer (NSCLC) patient survival and pemetrexed (PEM) treatment toxicity. Because of data heterogeneity, fixed or random effects models were chosen, and pooled HRs and 95% confidence intervals (CIs) were calculated. No correlation between MTHFR 677 C > T polymorphism and progression-free survival (PFS) or overall survival (OS) was detected in NSCLC patients; however, patients with the T allele benefited more than those with the wild-type allele. Two papers reported hematologic toxicity of single-agent PEM treatment in patients with the MTHFR 677 C > T polymorphism. However, data on MTHFR polymorphisms and toxicity could not be combined, even though publication bias and sensitivity analysis results were stable and reliable. We conclude that the MTHFR 677 C > T polymorphism could not predict PEM efficacy in NSCLC patients; however, the T allele may increase the risk of haematological toxicity. A large-scale clinical trial is recommended.

A novel compound heterozygous COL4A4 mutation in a Chinese family with Alport syndrome: A care case report.

RATIONALE: Alport syndrome (AS) is an inherited progressive renal failure, characterized by kidney disease, hearing loss, and eye abnormalities. PATIENT CONCERNS: A 7-year-old male child was admitted for persistent microscopic hematuria and proteinuria. DIAGNOSES: Combined with clinical manifestations, laboratory testing, pathological changes of kidney and sequencing results, the patient was diagnosed as AS. INTERVENTIONS: The patient was treated with ACEI and tacrolimus drugs for 2 years, but continued to have hematuria and proteinuria. Thus, a genetic analysis was performed using next-generation sequencing in four affected members from the family. OUTCOMES: The findings revealed triple compound heterozygous mutation of COL4A4: three novel variations, c.1045C>T (p. R349X), c.3505+1G>A (splicing), and c.2165G>A (p. G722D). LESSONS: This study was novel in finding that a triple variant of the COL4A4 gene simultaneously in trans and in cis. The effects of multiple mutation sites and the type of gene mutation in AS were also underlined.

The promotion of cervical cancer progression by signal transducer and activator of transcription 1-induced up-regulation of lncRNA MEOX2-AS1 as a competing endogenous RNA through miR-143-3p/VDAC1 pathway.

Long non-coding RNAs (lncRNAs) are the new regulators and biomarkers for various tumors. However, in cervical cancer (CC), the potential roles of lncRNAs are not well characterized. This research aimed at exploring the roles of MEOX2 antisense RNA 1(MEOX2-AS1) in CC progression and the underlying mechanisms. The examination of MEOX2-AS1 levels in CC specimens and cell lines was conducted by RT-PCR. Loss-of-function experiments were performed for the assays of proliferation, migration, and invasion of CC cells after various treatments. Animal experiments were applied for the determination of the effects of MEOX2-AS1 in vivo. Bioinformatics analysis, together with dual-luciferase reporter assays, was applied to demonstrate the possible relationships among MEOX2-AS1, miR-143-3p and VDAC1. In the paper, we reported that MEOX2-AS1 levels were distinctly upregulated in CC cells and tissues, and higher MEOX2-AS1 expressions indicated a poor clinical outcome. Besides, STAT1 could activate transcriptions of MEOX2-AS1 by binding directly to its promoter region. The silence of MEOX2-AS1 suppressed the metastatic and proliferative ability of CC cells, as revealed by functional assays. Mechanistically, MEOX2-AS1 sponged miR-143-3p to regulate VDAC1 expressions. Furthermore, miR-143-3p inhibitor reversed the anti-proliferation and anti-metastasis effect of MEOX2-AS1 knockdown. Overall, the data indicated that the MEOX2-AS1/miR-143-3p/VDAC1 pathway participated in CC progression, making it a novel therapeutic target for CC cures.

Tumorigenic effect of TERT and its potential therapeutic target in NSCLC (Review).

Non­small cell lung cancer (NSCLC), which accounts for ~85% of all lung cancer cases, is commonly diagnosed at an advanced stage and has a high patient mortality rate. Despite the increasing availability of treatment strategies, the prognosis of patients with NSCLC remains poor, with a low 5­year survival rate. This poor prognosis may be associated with the tumor heterogeneity of NSCLC, as well as its acquisition and intrinsic resistance to therapeutic drugs. It has been suggested that combination therapy with telomerase inhibition may be an effective strategy for the treatment of drug­sensitive and drug­resistant types of cancer. Telomerase is the key enzyme for cell survival, and ~90% of human cancers maintain telomeres by activating telomerase, which is driven by the upregulation of telomerase reverse transcriptase (TERT). Several mechanisms of telomerase reactivation have been described in a variety of cancer types, including TERT promoter mutation, epigenetic modifications via a TERT promoter, TERT amplification, and TERT rearrangement. The aim of the present study was to comprehensively review telomerase activity and its association with the clinical characteristics and prognosis of NSCLC, as well as analyze the potential mechanism via which TERT activates telomerase and determine its potential clinical application in NSCLC. More importantly, current treatment strategies targeting TERT in NSCLC have been summarized with the aim to promote discovery of novel strategies for the future treatment of NSCLC.

Abnormal thymic B cell activation and impaired T cell differentiation in pristane-induced lupus mice.

Changes in the thymus and potential mechanisms underlying the pathogenesis in pristane-induced lupus (PIL) mice are poorly understood. This study aimed to systematically and specifically examine changes in the thymus and the potential mechanisms responsible for immunological abnormalities in PIL mice. The results showed that PIL mice exhibit serious thymic hyperplasia, an elevated thymus index, a damaged histopathological structure and increased thymocyte apoptosis. We found that thymic T cell differentiation was impaired as the CD4+ CD8+ double-positive (DP) thymocyte frequency significantly decreased, becoming almost absent at 28 weeks after induction, while CD4 CD8- double-negative (DN) thymocytes and CD4+ CD8- single-positive (CD4+ SP) and CD4 CD8+ single-positive (CD8+ SP) cells were increased. This phenomenon might be explained by an inhibition of the DN-to-DP-cell transition and stimulation of DP cell conversion into CD4+ /CD8+ SP thymocytes. Moreover, we discovered a dramatic and abnormal increase in thymic B cells, that was associated with CD19, Irf8, Ebf1, Pax5, Irf4, Blk, CXCL13, CXCR5, CD79a, CD79b, Lyn, Syk, Btk, and BLNK gene accumulation, which exhibited positive interactions. We further verified that the mRNA expression of these genes was significantly upregulated and consistent with the RNA-seq results. These results suggest a role of these genes in the increase of B cells in the thymus of PIL mice. In summary, our results showed the changes in the thymus in PIL and elucidated the immunologic abnormalities of increased B cells, potentially providing insight into the associated molecular mechanisms and facilitating further research.

Changes in the distribution of endogenous hormones in Phyllostachys edulis 'Pachyloen' during bamboo shooting.

In this study, we investigated the changes in the distribution and regulation of endogenous hormones in Phyllostachys edulis 'Pachyloen' during bamboo shooting. Enzyme-linked immunosorbent assay was used to measure the mass fractions of indole-3-acetic acid (IAA), gibberellic acid (GA), zeatin riboside (ZR), and abscisic acid (ABA) in rhizomes, shoots, and maternal bamboo organs during shoot sprouting, shoot growth, and new-bamboo formation. Measurements were compared among bamboo parts and developmental periods. The overall mass fractions of IAA and ABA were significantly higher than those of ZR and GA, driven by differences among bamboo parts and developmental periods. The abundance of each endogenous hormone varied among bamboo parts and developmental periods. During bamboo shooting, ABA had the highest mass fraction in all bamboo parts sampled, followed by IAA, GA, and ZR. Among bamboo parts, rhizomes had more IAA, ZR, and GA than the other parts, but significantly less ABA. Winter shoots had higher ZR: IAA and GA: IAA ratios than rhizomes and maternal bamboo organs. During shoot growth, ABA was the most abundant hormone in rhizomes and maternal bamboo organs, followed by IAA, ZR, and GA. In contrast, IAA was the most abundant hormone in spring shoots, followed by ABA, ZR, and GA. Maternal bamboo organs had a significantly higher ZR: GA ratio, and significantly lower IAA: ABA, ZR: ABA, and GA: ABA ratios than rhizomes. Spring shoots had significantly higher IAA: ABA, ZR: ABA, and GA: ABA ratios than rhizomes and maternal bamboo organs; significantly higher ZR mass fractions, and ZR: GA and ZR: IAA ratios and significantly lower ABA mass fractions than rhizomes; and significantly higher GA: IAA ratio than maternal bamboo organs. During new-bamboo formation, ABA was the most abundant hormone in rhizomes, winter shoots, and maternal bamboo organs, followed by IAA, ZR, and GA. Maternal bamboo organs had significantly lower IAA mass fractions and significantly higher ABA mass fractions than rhizomes and new bamboo tissue. IAA and ABA abundances exhibited an inverse relationship in rhizomes and maternal bamboo organs. GA: ABA and GA: IAA ratios decreased gradually and other hormone ratios exhibited parabolic trends over the bamboo-shooting period, with the highest ratios observed in new bamboo tissues. Overall, the coordination or antagonism among endogenous hormones plays a key regulatory role in bamboo shoot growth. The formation of thick walls in P. edulis 'Pachyloen', one of its major traits, may be partially attributed to the relatively high IAA and ZR and low GA mass fractions.

A small natural molecule CADPE kills residual colorectal cancer cells by inhibiting key transcription factors and translation initiation factors.

Residual disease is the major cause for colorectal cancer (CRC) relapse. Herein, we explore whether and how a natural molecule CADPE killed heterogenic populations in a panel of CRC cell lines with KRAS/BRAF mutations that are natively resistant to EGFR- or VEGFR-targeted therapy, without sparing persistent cells, a reservoir of the disease relapse. Results showed that CADPE killed the tumor bulk and residual cells in the panel of CRC cell lines, rapidly inactivated c-Myc, STAT3, and NF-κB, and then decreased the protein levels of key signaling molecules for CRC, such as ß-catenin, Notch1, and the nodes of mTOR pathways; eukaryotic translation initiation factors (eIF4F); anti-apoptotic proteins (Bcl-xl, Mcl-1, and survivin); and stemness-supporting molecules (CD133, Bim-1, and VEGF). In terms of mechanism of action, concurrent downregulation of Mcl-1, Bcl-xl, and survivin was necessary for CADPE to kill CRC bulk cells, while additional depletion of CD133 and VEGF proteins was required for killing the residual CRC cells. Moreover, the disabled c-Myc, STAT3, NF-κB, and eIF4F were associated with the broadly decreased levels of anti-apoptosis proteins and pro-stemness proteins. Consistently, CADPE suppressed CRC tumor growth associated with robust apoptosis and depleted levels of c-Myc, STAT3, NF-κB, eIF4F, anti-apoptotic proteins, and pro-stemness proteins. Our findings showed the promise of CADPE for treating CRC and suggested a rational polytherapy that disables c-Myc, STAT3, NF-κB, and eIF4F for killing CRC residual disease.

Percutaneous radiofrequency ablation is superior to hepatic resection in patients with small hepatocellular carcinoma.

BACKGROUND: It is not known whether percutaneous radiofrequency ablation (PRFA) has the same treatment efficacy and fewer complications than laparoscopic resection in patients with small centrally located hepatocellular carcinoma (HCC). AIM: To compare the effectiveness of PRFA with classical laparoscopic resection in patients with small HCC and document the safety parameters. METHODS: In this retrospective study, 85 patients treated with hepatic resection (HR) and 90 PRFA-treated patients were enrolled in our hospital from July 2016 to July 2019. Treatment outcomes, including major complications and survival data, were evaluated. RESULTS: The results showed that minor differences existed in the baseline characteristics between the patients in the two groups. PRFA significantly increased cumulative recurrence-free survival (hazard ratio 1.048, 95%CI: 0.265-3.268) and overall survival (hazard ratio 0.126, 95%CI: 0.025-0.973); PRFA had a lower rate of major complications than HR (7.78% vs 20.0%, P < 0.05), and hospital stay was shorter in the PRFA group than in the HR group (7.8 ± 0.2 d vs 9.5 ± 0.3 d, P < 0.001). CONCLUSION: Based on the data obtained, we conclude that PRFA was superior to HR and may reduce complications and hospital stay in patients with small HCC.

Pharmacogenetic impact of UGT1A1 polymorphisms on pulmonary neuroendocrine tumours treated with metronomic irinotecan-based chemotherapy in Chinese populations.

OBJECTIVES: To evaluate the effects of UGT1A1*6 and UGT1A1*28 polymorphisms on the safety and efficacy of metronomic irinotecan-based chemotherapy (IBC) in Chinese patients with pulmonary neuroendocrine tumours (PNTs). METHODS: Sixty-eight PNT patients who received metronomic IBC were observed. The quantitative fluorescent polymerase chain reaction was used to detect UGT1A1*6 and UGT1A1*28 polymorphisms. The follow-up data were collected to investigate the relationship between different genotypes and adverse drug reactions. The clinical outcomes of metronomic IBC were also evaluated. KEY FINDINGS: In the genotype-toxicity association analysis, patients with homozygous UGT1A1*6 had the highest incidence of grade 3-4 diarrhoea (P = 0.010). Compared to other groups, patients with the haplotype of UGT1A1*28 showed a trend towards an increased incidence of grade 4 neutropaenia (P = 0.047). A higher incidence of grade 3-4 leucopaenia was found in groups with UGT1A1*1/*28 (P = 0.023) and UGT1A1*28/*28 (P = 0.022). Grade 1 total bilirubin elevation was associated with the homozygous UGT1A1*6 mutation (P = 0.027) or any UGT1A1*6 variants (P = 0.047). However, neither UGTA1A*28 nor UGT1A1*6 showed any significant association with tumour response or clinical outcomes. CONCLUSIONS: The impact of UGT1A1 polymorphisms varies in different irinotecan-based chemotherapies. UGT1A1*6 and UGTA1A*28 were useful for the prediction of irinotecan-related severe toxicity in Chinese PNT patients treated with metronomic IBC.

Fibroblast growth factor 21 prolongs lifespan and improves stress tolerance in the silkworm, Bombyx mori.

BACKGROUND: Fibroblast growth factor 21 (FGF21), an FGF family member, is an atypical hormone and pro-longevity factor. METHODS: To better understand of the effects of exogenous administration of FGF21 on lifespan and stress tolerance, and the underlying molecular basis, we used the silkworm, Bombyx mori, as an experimental animal model to evaluate FGF21's pharmaceutical effects. RESULTS: Lifespan was significantly prolonged in female silkworms with FGF21 replenishment, whereas no effect was observed in the male silkworms. FGF21 replenishment also significantly improved the activity of antioxidant systems such as glutathione-S-transferase (GST) and superoxide dismutase (SOD) and significantly decreased malondialdehyde (MDA) content. Moreover, FGF21 was found to play a critical role in enhancing stress resistance, including ultraviolet (UV) irradiation tolerance and thermotolerance. Furthermore, AMPK, FoxO, and sirtuins were activated by FGF21 and may be responsible for the prolonged lifespan and enhanced antioxidant activity observed in silkworms. CONCLUSIONS: Collectively, the results suggest the molecular pathways underlying of FGF21-induced longevity and stress tolerance, and support the use of silkworms as a promising experimental animal model for evaluating the pharmaceutical effects of small molecules.

Carfilzomib inhibits the growth of lung adenocarcinoma via upregulation of Gadd45a expression.

Proteasome inhibitors have shown remarkable success in the treatment of hematologic neoplasm. There has been a lot of attention to applying these drugs for solid tumor treatment. Recent preclinical study has signified the effectiveness on cell proliferation inhibition in lung adenocarcinoma treated by carfilzomib (CFZ), a second generation proteasome inhibitor. However, no insight has been gained regarding the mechanism. In this study, we have systematically investigated the CFZ functions in cell proliferation and growth, cell cycle arrest, and apoptosis in lung adenocarcinoma cells. Flow cytometry experiments showed that CFZ significantly induced G2/M cell cycle arrest and apoptosis in lung adenocarcinoma. MTS and colony formation assays revealed that CFZ substantially inhibited survival of lung adenocarcinoma cells. All results were consistently correlated to the upregulation expression of Gadd45a, which is an important gene in modulating cell cycle arrest and apoptosis in response to physiologic and environmental stresses. Here, upregulation of Gadd45a expression was observed after CFZ treatment. Knocking down Gadd45a expression suppressed G2/M arrest and apoptosis in CFZ-treated cells, and reduced cytotoxicity of this drug. The protein expression analysis has further identified that the AKT/FOXO3a pathway is involved in Gadd45a upregulation after CFZ treatment. These findings unveil a novel mechanism of proteasome inhibitor in anti-solid tumor activity, and shed light on novel preferable therapeutic strategy for lung adenocarcinoma. We believe that Gadd45a expression can be a highly promising candidate predictor in evaluating the efficacy of proteasome inhibitors in solid tumor therapy.

A study of the relationship between human infection with avian influenza a (H5N6) and environmental avian influenza viruses in Fujian, China.

BACKGROUND: Avian influenza A (H5N6) virus poses a great threat to the human health since it is capable to cross the species barrier and infect humans. Although human infections are believed to largely originate from poultry contaminations, the transmissibility is unclear and only limited information was available on poultry environment contaminations, especially in Fujian Province. METHODS: A total of 4901 environmental samples were collected and tested for Avian Influenza Virus (AIV) from six cities in Fujian Province through the Fujian Influenza Surveillance System from 2013 to 2017. Two patient-related samples were taken from Fujian's first confirmed H5N6 human case and his backyard chicken feces in 2017. Chi-square test or Fisher's exact probability test was used to compare the AIV and the viral subtype positive rates among samples from different Surveillance cities, surveillance sites, sample types, and seasons. Phylogenetic tree analysis and molecular analysis were conducted to track the viral transmission route of the human infection and to map out the evolutions of H5N6 in Fujian. RESULTS: The overall positive rate of the H5 subtype AIVs was 4.24% (208/4903). There were distinctive differences (p < 0.05) in the positive rates in samples from different cities, sample sites, sample types and seasons. The viruses from the patient and his backyard chicken feces shared high homologies (99.9-100%) in all the eight gene segments. Phylogenetic trees also showed that these two H5N6 viruses were closely related to each other, and were classified into the same genetic clade 2.3.4.4 with another six H5N6 isolates from the environmental samples. The patient's H5N6 virus carried genes from H6N6, H5N8 and H5N6 viruses originated from different areas. The R294K or N294S substitution was not detected in the neuraminidase (NA). The S31 N substitution in the matrix2 (M2) gene was detected but only in one strain from the environmental samples. CONCLUSIONS: The H5 subtype of AIVs has started circulating in the poultry environments in Fujian Province. The patient's viral strain originated from the chicken feces in his backyard. Genetic reassortment in H5N6 viruses in Fujian Province was indicated. The H5N6 viruses currently circulating in Fujian Province were still commonly sensitive to Oseltamivir and Zanamivir, but the resistance against Amantadine has emerged.

[Pathogens and clinical features of preterm infants with sepsis].

OBJECTIVE: To investigate the pathogen composition and clinical features of preterm infants with sepsis, and to provide a basis for early identification and treatment of sepsis in preterm infants. METHODS: A retrospective analysis was performed for the clinical data of 371 preterm infants with sepsis who had a positive blood culture between January 2014 and May 2018. According to the time of onset, the preterm infants were divided into an early-onset group (an age of onset of <7 days) with 73 preterm infants and a late-onset group (an age of onset of ≥7 days) with 298 preterm infants. The two groups were compared in terms of pathogen composition and clinical features (initial symptoms, laboratory examination results at the time of onset, comorbidities, and prognosis). RESULTS: There was a higher proportion of infants with Klebsiella pneumoniae infection in the late-onset group (P<0.05), while there was a higher proportion of infants with Escherichia coli, Streptococcus agalactiae or Listeria infection in the early-onset group (P<0.05). The early-onset group had a significantly higher proportion of infants with dyspnea than the late-onset group (P<0.05). Compared with the late-onset group, the early-onset group had significantly shorter time to negative conversion of blood culture, duration of antibiotic use before infection, and indwelling time of deep venous catheterization (P<0.05), and the late-onset group had a significantly higher incidence rate of neonatal necrotizing enterocolitis than the early-onset group (P<0.05). The early-onset group had a significantly higher rate of treatment withdrawal than the late-onset group (P<0.05). CONCLUSIONS: Preterm infants with sepsis lack typical clinical manifestations and laboratory examination results at the time of onset. There are certain differences in pathogen composition and clinical features between preterm infants with early- and late-onset sepsis. Possible pathogens for sepsis should be considered based on age in days at the time of onset and related clinical features.

A rare cutaneous phototoxic rash after vandetanib therapy in a patient with thyroid cancer: A case report.

RATIONALE: Vandetanib is effective for treating symptomatic or progressive medullary thyroid cancer (MTC) in patients with unresectable locally advanced or metastatic disease, but its toxicity such as photosensitivity reactions should be considered. It is a rare adverse effect of this drug but might cause severe morbidity and even mortality. PATIENT CONCERNS: A 26-year man with MTC developed phototoxic rashes on the sun-exposed areas of his shin after 15 days from the initiation of vandetanib treatment. Grade II skin toxicity was evaluated based on the Common Terminology Criteria for Adverse Events standard. DIAGNOSES: Drug-induced phototoxic rash. INTERVENTIONS: The vandetanib dose was reduced by 30%, and the application of topical steroids and sunscreen was adopted. OUTCOMES: After dose reduction of vandetanib, the symptoms of vandetanib-induced phototoxic rash resolved, although residual pigmentation was observed. LESSONS: Close attention should be paid to the adverse effect of vandetanib, phototoxic rash, and patients should be advised on the prevention and treatment measures.

Synthesis and antiproliferative activities of aminoalkylated polymethoxyflavonoid derivatives.

A series of novel aminoalkylated polymethoxyflavonoid derivatives 3-11 was synthesised from 5-hydroxy-3,7,3',4'-tetramethoxyflavonoid (1) through extending alkoxy chain at the 5-position, and introducing amine hydrogen bond receptor at the end of the side chain. Their antiproliferative activities were evaluated in vitro on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3). The results showed that all the target compounds exhibited antiproliferative activities against investigated cancer cells with IC50 values of 9.51-53.33 µM. Compounds 5, 7, 8, 11 on Hela cells and compounds 4-9, 11 on HCC1954 exhibited more potency as compared to positive control cis-Platin.