[Pembrolizumab plus nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma: a prospective phaseâ ¡study].

Objective: To evaluate the efficacy and safety of pembrolizumab plus nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma (R/M HNSCC). Methods: This was a prospective, single-arm, open label, phase 2 clinical study enrolling patients at the Cancer Hospital of the Chinese Academy of Medical Sciences with R/M HNSCC treated with pembrolizumab plus nab-paclitaxel and cisplatin or carboplatin. After six cycles of treatment, patients received pembrolizumab as maintenance therapy until disease progression or intolerable toxicity or completion of 35 cycles of treatment. The primary endpoint was objective response rate, and secondary endpoints included overall survival, progression-free survival, and safety profile. Efficacy was evaluated according to the response evaluation criteria in solid tumors 1.1, survival analysis was performed using the Kaplan-Meier method, and adverse events were assessed using the America National Cancer Institute Common Terminology Criteria for Adverse Events 5.0. Results: A total of 30 patients with R/M HNSCC were enrolled from 23 April 2021 to 22 March 2023, including 28 males and 2 females, with a median age of 67 years. The median follow-up time was 14.5 months, the objective response rate was 70.0%, the disease control rate was 96.7%, and the median progression-free survival and overall survival of all patients were 11.6 months and 18.8 months, respectively. Median duration of response was up to 17.3 months. Grade≥3 treatment-related adverse events were leukopenia (26.7%), neutropenia (26.7%), peripheral neurotoxicity (3.3%), rash (3.3%), hyperalgesia (3.3%), and immune-related pneumonitis (3.3%). The most common immune-related adverse event was hypothyroidism (40.0%). Conclusion: Pembrolizumab combined with nab-paclitaxel and platinum shows encouraging antitumor activity accompanied with a manageable safety profile in untreated R/M HNSCC patients in China.

SLC7A11-associated ferroptosis in acute injury diseases: mechanisms and strategies.

Ferroptosis is a kind of iron-dependent renewal programmed death. Its main mechanism is to catalyze the unsaturated fatty acids highly expressed on the cell membrane under the effect of divalent iron, to produce lipid peroxidation, thus inducing cell death. SLC7A11 is a known iron death-related factor. It has been proved that iron death is involved in the occurrence and development of acute diseases, but the specific mechanism is unknown. The purpose of this review is to highlight the regulatory properties of SLC7A11 and gain a deeper understanding of its role in ferroptosis-related acute injury diseases. This is a narrative review. PubMed was used as the main source to randomly implement literature search strategy to index Scopus articles. No specific terms are used. Studies have shown that SLC7A11 may affect the sensitivity of cells to iron ptosis by regulating it at the transcriptional or post-transcriptional level, which is related to the pathology of many acute injury diseases, such as acute lung injury (ALI), acute kidney injury (AKI), acute liver injury, myocardial ischemia-reperfusion injury, and acute cerebral hemorrhage. In order to clarify this point, more and more researchers turn their attention to the study of the specific mechanism between SLC7A11 and ferroptosis-related acute injury diseases. In summary, this review summarized some specific mechanisms by which ferroptosis could be controlled by SLC7A11 and clarified the underlying mechanisms of a series of diseases caused by SLC7A11-associated ferroptosis. It also provided more scientific justification for the clinical application of targeting ferroptosis in preventing and treating various diseases.

Prognostic alternative splicing regulatory network of splicing events in acute myeloid leukemia patients based on SpliceSeq data from 136 cases.

This study aimed to create prognostic signatures to predict AML patients' survival using alternative splicing (AS) events. The AS data, RNA sequencing data, and the survival statistics of 136 AML patients were obtained from The Cancer Genome Atlas (TCGA) and TCGA SpliceSeq databases. Total 34,984 AS events generated from 8,656 genes, 2,583 of which were survival-associated AS events, were identified using univariate Cox regression. The prognostic models constructed using independent survival-associated AS events revealed that low-risk splicing better predicted patients' survival. ROC analysis indicated that the predictive efficacy of the alternate terminator model was best in the area under the curve at 0.781. Enrichment analysis revealed several important genes (TP53, BCL2, AURKB, PPP2R1B, FOS, and BIRC5) and pathways, such as the protein processing pathway in the endoplasmic reticulum, RNA transport pathway, and HTLV-I infection pathway. The splicing network of splicing events and factors revealed interesting interactions, such as the positive correlation between HNRNPH3 and CALHM2-13010-AT, which may indicate the potential splicing regulatory mechanism. Taken together, survival-associated splicing events and the prognostic signatures for predicting survival can help provide an overview of splicing in AML patients and facilitate clinical practice. The splicing regulatory network may improve the understanding of spliceosomes in AML.

Effects of calcium on the uptake and elimination of cadmium and zinc in Asiatic clams.

We examined the effects of Ca, one of the major ions contributing to water hardness, on the uptake and elimination of Cd and Zn in the Asiatic clam Corbicula fluminea, a common bivalve species in the rivers and streams of Southern China. Over the wide range of dissolved Cd (4.5 to 446 nM) and Zn (15.3 to 1529 nM) concentrations, uptake of both metals increased with increasing dissolved metal concentration, showing Michaelis-Menten-type saturation kinetics. At each tested metal concentration, increased Ca concentration led to a significantly lower metal uptake. When the Ca, Cd, Zn concentrations were expressed as free-ion activities, Cd and Zn uptake data fitted the Michaelis-Menten inhibition model well. We also quantified the effects of the two Ca blockers on metal uptake by the clams. Verapamil significantly inhibited the uptake Cd and Zn, but the inhibitive effect of lanthanum on metal uptake was more evident for Cd than for Zn. Ca did not significantly affect the assimilation efficiency of either metal from ingested phytoplankton, nor did it affect the elimination of the two metals during a 1-month depuration period. Our study has shown that Ca inhibited the uptake of metals from water; such an effect could be predicted based on the free-metal ion activities. Ca did not seem to have a direct effect on metal assimilation from food or metal elimination from the bivalve.

Transmission of hepatitis C virus infection to tree shrews.

Although hepatitis C virus (HCV) infection can be reproduced in chimpanzees, these animals are rare and expensive. Tree shrews (tupaias) are small animals, closely related to primates, which adapt easily to a laboratory environment. In this work we have investigated the susceptibility of Tupaia belangeri chinensis to HCV infection. Tupaias caught in the wild in Yunnan (China) were inoculated in China with HCV genotype 1b (study A) and in Spain with a mixture of genotypes 1b, 1a, and 3 (study B). In study B tupaias were divided into three groups: group I was inoculated without previous manipulation, group II received 750 cGy of X-ray whole-body irradiation before inoculation, and group III was used as control. Transient or intermittent viremia occurred in 34.8% (8/23) and anti-HCV in 30.4% (7/23) of tupaias in study A. In study B a transient viremia was detected in 20% (2/10) in group I and in 50% (2/4) in group II. Anti-HCV was found in 1 tupaia from group I and in 3 from group II: Viremia lasted for longer and anti-HCV tended to reach higher titers in animals which received total body irradiation. ALT elevations and nonspecific pathological changes occurred in inoculated tupaias; however, the wild nature of the animals precludes the interpretation of these changes as solely due to HCV infection. In summary our results show that T.b. chinensis are susceptible to HCV and that whole-body irradiation may possibly increase the efficiency of the infection. These animals may serve as an in vivo system for culturing HCV and addressing pathophysiological and therapeutic issues of HCV infection.

Anticonflict effect of MK-801 in rats: time course and chronic treatment studies.

The present study examined the time course and chronic treatment effects of the noncompetitive N-methyl-D aspartate (NMDA) antagonist, MK-801 (dizocilpine), on conflict behavior in the conditioned suppression of drinking (CSD) paradigm, a repeated-measures conflict task. In daily 10-min sessions, water-restricted rats drank from a tube that was occasionally electrified (0.25- or 0.5-mA shocks signaled by a tone). Trained subjects (4 weeks of CSD testing) exhibited stable baselines for both punished responding and unpunished responding. In the first experiment, the effects of MK-801 administered IP were determined in female and male rats following a range of pretreatment intervals (i.e., 0.5-48 h). In female rats, 0.2 mg/kg MK-801 exerted an anticonflict effect at pretreatment intervals of 10-36 h, but not before 10 h or after 36 h. In male rats, qualitatively similar results were obtained; MK-801 (0.4 mg/kg) exerted anticonflict effects following pretreatment intervals of 6-14 h, but not before 6 or after 14 h. In the second experiment, chronic treatment of female rats with 0.04, 0.01, or 0.2 mg/kg MK-801 resulted in a dose-dependent anticonflict effect in CSD paradigm, which remained stable over the course of 5 weeks of chronic treatment. Punished responding returned to pretreatment levels within 2-3 days after discontinuation of chronic treatment with MK-801. These data suggest that MK-801 exerts a delayed anticonflict effect in both female and male rats with a qualitatively similar pattern, and that there is no tolerance to the anticonflict effect of MK-801 with chronic treatment.

Genotypes of hepatitis C virus in Guangxi province, southern China.

Hepatitis C virus (HCV) has been subdivided into at least four genotypes, and the prevalence of each genotype has been reported to differ widely in different countries. Of 304 patients with chronic liver diseases (68 with chronic hepatitis, 50 with liver cirrhosis and 186 with hepatocellular carcinoma) from Guangxi Province in southern China, only 9 (3.0%) had antibodies to HCV as determined by a second-generation enzyme immunoassay with a cut-off index of 2.0 or more. The HCV genotypes of these nine cases were examined using polymerase chain reaction with type-specific primers deduced from putative core gene. Seven of the nine cases had type II infection and the other two cases showed double infection with types II and IV. These findings indicate that the predominant HCV genotype in the Guangxi area is type II, as is the case in Japan, although the prevalence of HCV infection in patients with chronic liver diseases is much lower.

A low prevalence of anti-hepatitis C virus antibody in patients with hepatocellular carcinoma in Guangxi Province, southern China.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) in southern China, including Guangxi Province, is among the highest in the world. Investigations of the etiology of HCC in this area have focused on hepatitis B virus (HBV) and aflatoxin. However, hepatitis C virus (HCV) has been shown to be a possible pathogenic agent for HCC in a number of countries. METHODS: Antibodies to HCV (anti-HCV), determined by second-generation enzyme immunoassay, and hepatitis B surface antigen (HBsAg) were assayed in the sera of 186 patients with HCC and 48 healthy control subjects from Guangxi Province in southern China. RESULTS: HBsAg was detected in 131 (70.4%) of 186 patients with HCC, whereas only 10 (5.4%) patients were found to be positive for anti-HCV. The prevalence of anti-HCV in patients with HBsAg-positive HCC was 6.9% (9 of 131) and that in patients with HBsAg-negative HCC was 1.8% (1 of 55); there was no significant difference between these two groups. Anti-HCV was not detected in any of the healthy control subjects, in whom the prevalence of HBsAg was 10.4% (5 of 48). CONCLUSIONS: These findings indicate that HCV does not seem to play an important role in the development of HCC in Guangxi Province; however, HBV infection appears to be a major pathogenic factor for HCC in this area.

[Effect of ginseng on antiperoxidate injury in myocardium and erythrocytes in streptozocin-induced diabetic rats].

We have investigated the effect of ginseng on antiperoxidation in myocardium and erythrocytes of streptozocin-induced diabetic rats. In the group of ginseng administration (ginseng solution 0.2g/200g/day, lasting 15-16 days), there was a significant decrease in the level of fasting blood-glucose and lipid peroxide (LPO) in myocardium and erythrocytes, in comparing with that of model group, P < 0.05. The activity of superoxide dismutase (SOD) in myocardium and erythrocytes in group of ginseng administration was increased, P < 0.05, compared with that of model group and vitamin E treatment group. The mechanisms of antiperoxidation effect of ginseng might include the following: 1) By lowering the level of fasting blood-glucose, decreasing the rate of monosaccharide auto-oxidation and partially protecting the production of free radicals; 2) Elevating the activity of enzymatic free radicals scavenger in cells, such as SOD; 3) directly eliminating the superfluous free radicals.