[A retrospective study of postoperative adjuvant therapy following immunotherapy combined with targeted therapy and sequential curative surgical procedures for initially unresectable hepatocellular carcinoma].

Objective: To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma. Methods: This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People's Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method. Results: Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95%CI:93.4% to 100%) and 90.7%(95%CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95%CI:83.0% to 99.8%) and 71.3%(95%CI:58.7% to 86.5%). Conclusions: The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.

[Research progress on perioperative management of tooth extraction in denosumab-treated patients].

Denosumab, a human monoclonal antibody, is used for the prevention of malignant tumor-related bone events and the treatment of osteoporosis with high fracture risk. Since its approval in China in 2019, denosumab-related osteonecrosis of the jaw (DRONJ) has attracted increasing attention. DRONJ, similar to bisphosphonate-related osteonecrosis of the jaw, often occurs after tooth extraction and manifests as exposed bone necrosis, purulent discharge, facial swelling and pain, severely impacting patients' quality of life. However, the perioperative management strategies for DRONJ differ from those for bisphosphonate-related osteonecrosis of the jaw. This article summarizes the perioperative management strategies for high-risk DRONJ patients from aspects such as oral hygiene care, antibiotic use, drug discontinuation during the perioperative period, and surgical strategy selection, aiming to provide guidance for oral surgeons in managing tooth extraction in denosumab-treated patients.

RTA2 is involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in Candida albicans.

The calcineurin pathway has been reported to be essential for the development of azole resistance in Candida albicans. The depletion or ectopic over-expression of RTA2 increased or decreased susceptibility of C. albicans to azoles, respectively. CaCl(2)- induced activation of the calcineurin pathway in wildtype C. albicans promoted resistance to azoles, while the Ca(2+) chelator (EGTA), calcineurin inhibitors (FK506 and cyclosporin A) and the deletion of RTA2 blocked the resistance-promoting effects of CaCl(2). Furthermore, we found that RTA2 was up-regulated in a calcineurin-dependent manner. The depletion of RTA2 also made the cell membrane of C. albicans liable to be destroyed by azoles and RTA2 over-expression attenuated the destroying effects. Finally, the disruption of RTA2 caused an increased accumulation of dihydrosphingosine (DHS), one of the two sphingolipid long-chain bases, by decreasing release of DHS. In conclusion, our findings suggest that RTA2 is involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in C. albicans.

Prognostic and predictive values of CXCL10 in colorectal cancer.

BACKGROUND: The role of CXCL10 in progression and prognosis of colorectal cancer (CRC) has been studied for years, yet results remain controversial. AIM: This study aims to explore the relationship between CXCL10 and CRC progression and prognosis. METHODS: We evaluated plasma CXCL10 in CRC patients using ELISA. We also performed a meta-analysis of the associations between CXCL10 and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), relapse-free survival (RFS), and clinicopathological features. Finally, correlations between CXCL10 and methylation or immune infiltration were performed using TCGA data. RESULTS: ELISA analysis showed that CXCL10 was associated with age, red blood cells, blood platelets, and blood urea nitrogen. A separate analysis of 3,763 patients from 24 studies revealed that there were significant associations between low CXCL10 expression and OS (HR 1.25, 95% CI 1.01-1.53), DFS (HR 1.65, 95% CI 1.17-2.34), and RFS (HR 1.43, 95% CI 1.20-1.71) in CRC. Additionally, downregulated CXCL10 expression was significantly correlated with age [odds ratio (OR) 1.31, 95% CI 1.13-1.52], metastasis (OR 1.34, 95% CI 1.11-1.63), recurrence (OR 1.46, 95% CI 1.16-1.83), tumor location (OR 1.88, 95% CI 1.58-2.24), differentiation (OR 0.57, 95% CI 0.35-0.93), microsatellite instability (OR 0.23, 95% CI 0.15-0.35), BRAF mutation (OR 1.62, 95% CI 1.25-2.08), p53 mutation (OR 0.28, 95% CI 0.16-0.47), and CIMP (OR 0.27, 95% CI 0.17-0.43). Furthermore, significant associations were observed between CXCL10 and methylation and immune infiltration. CONCLUSIONS: The study suggests that CXCL10 might be a potential target for the treatment of CRC. TRIAL REGISTRATION: NCT03189992. Registered 4 June 2017, https://www.clinicaltrials.gov/ct2/show/study/NCT03189992?term=NCT03189992&rank=1 .

Compact high-power microwave divider and combiner.

A novel, compact, TM01-TE10 mode power divider and a novel, compact, four-way TE10-TM01 mode power combiner were theoretically designed and experimentally tested as a proof of principle. The theoretical and experimental S parameters are consistent with each other. High-power experiments show that their power capacities are no less than 1.5 GW and 3 GW, respectively. The devices have the merits of high power capacities and low insertion losses.

[Effect of Tibetan compound prescription on cardiac haemodynamics in experimental myocardial ischemia in dogs].

35 healthy and hybrid dogs were divided into the control group (5 dogs), ischemic group (15 dogs) and medicated group (15 dogs). The myocardial ischemia model was produced by ligating the left coronary artery between the branch 2 and 3 among the anterior descending branches. The effect of the herbs on the experimental myocardial ischemia was observed by measuring the Mean Artery Pressure (MAP), the Left Ventricular End Diastolic Pressure (LVEDP), the Heart Rate (HR), the Cardiac Output (CO) and the Cardiac Index (CI) etc. The results showed that the LVEDP was significantly increased and the MAP, the CO and the CI were lowered during the period of myocardial ischemia, which indicated the disorder of cardiac heaemodynamics after the myocardial ischemia, By taking the medicine through the duodenum in the medicated group, the CO was obviously increased during the period of myocardial ischemia and also the CI was elevated prominently. The investigation indicated that the medicine could reinforce the cardiac pump function and adjust the disorder of cardiac haemodynamics resulted from myocardial ischemia.

Pain as a mutual experience for patients, nurses and families: a perspective from Shanghai, China.

The author of this article visited China for the purpose of helping the faculty of the School of Nursing learn research skills by participating in research--a kind of learn by doing. Both investigators had conducted quantitative studies in the US--one with children and one with adults--that were adapted for use in China. Seeking to also include a qualitative study, the investigators explored several possible research areas. Because pain is a universal phenomena, it was chosen as the subject for the study using the qualitative methodology reported in the first part of this article.

The detection of 3 leptin receptor isoforms in crucian carp gill and the influence of fasting and hypoxia on their expression.

To understand leptin signaling pathway in the crucian carp (Carassius carassius), we cloned 3 leptin receptor isoform complementary DNAs (ie, the long form [cclpr-L], the short form [cclpr-s1], and the secreted form [cclpr-s2]). Variant cclpr-L had a 3,255-bp open reading frame and a complete intracellular domain with box 1 and box 2 consensus sequences. By contrast, cclpr-s1 contained only 4 amino acids in its intracellular domain, without the "box 1" motif, which is conserved among membrane-bound leptin receptor short isoforms in mammals. Variant cclpr-s2 had no transmembrane domain, suggesting that it is a soluble form of the receptor, and alternative splicing of cclpr-s2 mRNA employs a different mechanism for the generation of soluble leptin receptor by intron retention. The fasting-treated fish showed significantly lower cclpr-L mRNA levels in gill tissue than the control group, whereas cclpr-s2 mRNA levels did not vary significantly among the groups. Treatment with hypoxia significantly increased mRNA levels of both cclpr-L and cclpr-s2 in gill tissue. To our knowledge, this is the first study of leptin receptor isoforms expression in teleosts.

Candida albicans THI13 disruption affects production of monocytic cytokines.

INTRODUCTION: The Candida albicansTHI13 gene was identified by its homology to the Candida tropicalis CtNMT1 gene, which is involved in pyrimidine precursor biosynthesis. METHODS: Disruption of THI13 revealed that this gene played a minor role in thiamin biosynthesis in C. albicans. Purified human monocytes were incubated with C. albicans at the optimal Candida: monocyte ratio of 0.5 and cytokines in the supernatants were measured by enzyme-linked immunosorbent assay. RESULTS AND DISCUSSION: This experiment showed that the wild-type strain significantly induced interleukin-10 (IL-10) production but had little effect on IL-12 production, and that THI13 mutants had no significant effect on IL-10 production, though the IL-12 level was increased in the supernatants. These results suggest that THI13 is involved in the host effective immune response by regulating IL-10 and IL-12 production.

Altered protein profile of lymphocytes in an antigen-specific model of colitis: a comparative proteomic study.

OBJECTIVE: Lymphocytes are deeply involved in the initiation and perpetuation of inflammatory response in inflammatory bowel disease (IBD) and lymphocyte-derived proteins are associated with the pathogenesis of the disease. The aim of this study was to identify the altered protein profiles of lymphocytes from rats with colitis. METHODS: Colitis models were induced by colonic administration of trinitrobenzene sulfonic acid (TNBS) in 50% ethanol in male SD rats. Seven days after administration of TNBS/ethanol, lymphocytes were harvested from mesenteric lymph nodes (MLNs) and proteins were extracted. Two-dimensional polyacrylamide gel electrophoresis and PDQuest 2D-image-analysis software were used to display and analyze the protein spots. The differentially-expressed proteins were identified by tryptic in-gel digestion and mass spectrometry. Real-time RT-PCR was used for selected transcripts to validate the findings of the proteomics analysis. RESULTS: A total of 1,100 protein spots including 26 proteins with at least a two-fold difference in abundance between colitis and control groups were identified. Among all the detected spots, 17 were up-regulated and 9 were down-regulated. It was found that the altered proteins included the regulators of the cell cycle and cell proliferation, signal transduction factors, inflammatory factors, apoptosis-related proteins and metabolic enzymes. CONCLUSIONS: In lymphocytes of rats with TNBS-induced colitis, 26 altered proteins were identified. They involve inflammation, apoptosis, metabolism, and regulation of the cell cycle, cell proliferation, and signal transduction.

[Studies on response characteristics of Cl, Br, I of microwave plasma torch atomic emission detector for gas chromatography].

The present paper deals with a microwave plasma torch atomic emission detector for gas chromatography. Argon is used as support gas, carrier gas and make-up gas. The effect of oxygen scavenger gas on the detection performance for chlorine, bromine and iodine is discussed. Detection limits, dynamic ranges, relative standard deviations and response characteristics of GC-MPT-AED for chlorine, bromine and iodine in organic compounds were studied. The results are favorable in comparing with GC-ICP-AED.