Abnormal metabolism in hepatic stellate cells: Pandora's box of MAFLD related hepatocellular carcinoma.

Metabolic associated fatty liver disease (MAFLD) is a significant risk factor for the development of hepatocellular carcinoma (HCC). Hepatic stellate cells (HSCs), as key mediators in liver injury response, are believed to play a crucial role in the repair process of liver injury. However, in MAFLD patients, the normal metabolic and immunoregulatory mechanisms of HSCs become disrupted, leading to disturbances in the local microenvironment. Abnormally activated HSCs are heavily involved in the initiation and progression of HCC. The metabolic disorders and abnormal activation of HSCs not only initiate liver fibrosis but also contribute to carcinogenesis. In this review, we provide an overview of recent research progress on the relationship between the abnormal metabolism of HSCs and the local immune system in the liver, elucidating the mechanisms of immune imbalance caused by abnormally activated HSCs in MAFLD patients. Based on this understanding, we discuss the potential and challenges of metabolic-based and immunology-based mechanisms in the treatment of MAFLD-related HCC, with a specific focus on the role of HSCs in HCC progression and their potential as targets for anti-cancer therapy. This review aims to enhance researchers' understanding of the importance of HSCs in maintaining normal liver function and highlights the significance of HSCs in the progression of MAFLD-related HCC.

A systematic review and meta-analysis comparing tumor progression and complications between radiofrequency ablation and thyroidectomy for papillary thyroid carcinoma.

Background: Papillary thyroid cancer (PTC) is the most frequent thyroid cancers worldwide. The efficacy and acceptability of radiofrequency ablation (RFA) in the treatment of PTC have been intensively studied. The aim of this study is to focus on extra detailed that may influent for PTC or papillary thyroid microcarcinoma (PTMC). Materials and methods: We identified a total of 1,987 records of a primary literature searched in PubMed, Embase, Cochrane Library, and Google Scholar by key words, from 2000 to 2022. The outcome of studies included complication, costs, and local tumor progression. After scrutiny screening and full-text assessment, six studies were included in the systematic review. Heterogeneity was estimated using I2, and the quality of evidence was assessed for each outcome using the GRADE guidelines. Results: Our review enrolled 1,708 patients reported in six articles in the final analysis. There were 397 men and 1,311 women in the analysis. Two of these studies involved PTC and four focused on PTMC. There were 859 patients in the RFA group and 849 patients in the thyroidectomy group. By contrast, the tumor progression of RFA group was as same as that surgical groups [odds ratio, 1.31; 95% CI, 0.52-3.29; heterogeneity (I2 statistic), 0%, p = 0.85]. The risk of complication rates was significantly lower in the RFA group than that in the surgical group [odds ratio, 0.18; 95% CI, 0.09-0.35; heterogeneity (I2 statistic), 40%, p = 0.14]. Conclusions: RFA is a safe procedure with a certain outcome for PTC. RFA can achieve a good efficacy and has a lower risk of major complications.

Transarterial chemoembolization combined with metformin improves the prognosis of hepatocellular carcinoma patients with type 2 diabetes.

Objective: The study aims to investigate the effect of metformin on Hepatocellular carcinoma (HCC) patients with type 2 diabetes mellitus (T2DM) who received transarterial chemoembolization (TACE) for the first time. Methods: From January 2016 to December 2019, T2DM patients diagnosed with HCC in Shandong Cancer Hospital and treated with TACE were included in this retrospective study. Overall survival (OS) and Progression-free survival (PFS) were compared between patients treated with metformin and other antidiabetics. Univariate and multivariate Cox regression models were used to evaluate the independent risk factors associated with OS and PFS. And sub-analysis was performed to investigate whether metformin could give a survival advantage in each Barcelona Clinic Liver Cancer (BCLC) stage of HCC. Propensity score matched (PSM) analyses based on patient and tumor characteristics were also conducted. Results: A total of 123 HCC patients with T2DM underwent TACE, of which 50 (40.65%) received treatment with metformin. For the whole cohort, the median OS (42 vs 32 months, p=0.054) and PFS (12 vs 7 months, P=0.0016) were longer in the metformin group than that in the non-metformin group. Multi-analysis revealed that BCLC stage, BMI (Body Mass Index), and metformin use were independent predictors of OS. Metformin use was independently associated with recurrence. After PSM, 39 matched pairs were identified. The use of metformin was associated with a numerically longer m OS (43 vs 35 months, P=0.183) than the use of other anti-diabetics. And the difference in median PFS (13 vs 7 months, p=0.018) between the metformin group and non-metformin group remained significant. Conclusion: The combination of transarterial chemoembolization and metformin may be associated with better OS and PFS in HCC patients with T2DM.

Overweight with HBV infection limited the efficacy of TACE in hepatocellular carcinoma by inhibiting the upregulated HMGB1.

BACKGROUND: Transarterial chemoembolization (TACE) is an effective treatment for patients with hepatocellular carcinoma (HCC). However, the impact of hepatitis B viral (HBV) infection and body mass index (BMI) on TACE is controversial. The present study aimed to compare the influence of HBV and high BMI on TACE outcomes in advanced HCC. METHODS: Based on HBV infection history and BMI, patients were assigned to different subgroups. Blood samples were collected and analyzed by an enzyme-linked immunosorbent assay (ELISA) kit. The primary endpoint was progression-free survival (PFS) and the overall survival (OS) in the population. RESULTS: Compared to overweight combined HBV patients who received TACE, people with normal weight or no viral infection had significantly better OS and PFS. Sex, age, portal vein tumor thrombus, BCLC, ECOG, and tumor diameter are the main risk factors affecting PFS and OS. Except for the postoperative fever, no significant difference was detected in adverse reactions. Irrespective of TACE, the average expression of HMGB1 in hepatitis or obesity patients was higher than that in normal individuals and did not show upregulation after TACE. Patients without overweight or HBV infection had a low expression of serum HMGB1 that was substantially upregulated after TACE. CONCLUSIONS: In this study, overweight combined HBV infection patients had shorter PFS and OS than other HCC patients. Thus, HBV and BMI maybe two factors affecting the efficacy of TACE via upregulated HMGB1.

HMGB1, the Next Predictor of Transcatheter Arterial Chemoembolization for Liver Metastasis of Colorectal Cancer?

HMGB1 is an important mediator of inflammation during ischemia-reperfusion injury on organs. The serum expression of HMGB1 was increased significantly on the 1st day after TACE and decreased significantly which was lower on the 30th day after TACE. Tumor markers of post-DEB-TACE decreased significantly. The correlational analysis showed that patients with low HMGB1 expression had lower risks of fever and liver injury compared those with the higher expression, while the ORR is relatively worse. Patients with lower expression of HMGB1 had longer PFS, better efficacy, and higher quality of life. With the high post-expression, the low expression had lower incidence of fever and liver injury too. There was no statistical difference in the one-year survival among the different groups. The quality of life of all patients was improved significantly. The over-expression of HMGB1 in LMCRC is an adverse prognostic feature and a positive predictor of response to TACE.

Efficacy of radiofrequency ablation and microwave ablation in the treatment of thoracic cancer: A systematic review and meta-analysis.

BACKGROUND: Radiofrequency ablation and microwave ablation are frequently prescribed for thoracic cancer. However, few writers have been able to draw on any systematic research into the differences between the two ablation methods. METHODS: A literature search was carried out using Embase, PUBMED, Web of Science, Cochrane Library, and CNKI databases, with additional searches carried out manually using terms associated with thoracic cancer and thermal ablation. Then we used Google Scholar for a complementary search. Data were extracted from studies of patients that underwent radiofrequency ablation or microwave ablation, and the investigator carried out efficacy evaluation and follow up. The data obtained from the literature were summarized and analyzed using Cochrane Revman software Version 5.3 and SPSS 22.0. RESULTS: There were seven comparative studies, but no randomized studies identified for data extraction; 246 patients received radiofrequency ablation therapy and 319 controls received microwave ablation. There was no significant difference in the six-month, one-year, two-year, and three-year survival rates, and adverse reactions were found in the two treatments. For patients' long-term survival rate, the two treatments can achieve a similar survival time. CONCLUSION: In the treatment of thoracic cancer, microwave ablation can achieve the same efficacy as radiofrequency ablation.

[Chromosomal studies of germ cells in diploid and polyploid fish produced by distant crossing].

By observing the chromosomal spreads of germ cells and tissue sections, we studied the chromosomal spreads of germ cells in diploid and polyploid fish produced by distant crossing. The samples covered the second generation of hybrids of red crucian carp (Carassius auratus red var.) (female) x common carp (Cyprinus carpio) (male) (2n = 100) (F2), allotetraploid hybrids of red crucian carp (female) x common carp (male)(4n = 200), triploid hybrids of gold fish (female)x allotetraploid (male) (3n = 150), the second generation of the gynogenetic progeny of allotetraploid hybrids (G2) (2n = 100), and the common carp (2n = 100) used as a control. The results demonstrated that chromosomal number of spermotogonia in common carp was equal to that of their somatic cell (2n = 100), while the chromosomal number of germ cells in diploid hybrid fish and polyploid hybrid fish had doubled obviously, and the frequent of chromosomal doubling in spermotogonia of F2 appeared especially high, accounting for 21.6% of all examined chromosomal spreads, which provided directly cytological evidence for the production of unreduced diploid gametes in F2 and also indicated that distant crossing was an important factor to lead to chromosomal doubling in germ cell. This research had important significance in studies on the formation of polyploidy fish and fish breeding.

Induction of gynogenesis in Japanese crucian carp (Carassius cuvieri).

Diploid gynogenesis was induced in Japanese crucian carp (Carassius cuvieri) eggs using UV-irradiated genetically inactive spermatozoa from mirror carp (Cyprinus carpio L.) or blunt snout bream (Megalobrama amblycephala), with or without cold shock. The optimal radiation dosage was 4,200 mJ/cm2 and 3,600 mJ/cm2 for mirror carp and blunt snout bream sperm, respectively. At this dosage and without cold shock, the yields were (32.4 +/- 3.3)% vs. (33.8 +/- 1.4)% gynogenetic haploids and (0.7 +/- 0.3)% vs. (0.5 +/- 0.3)% hybrid diploids, respectively. At the optimal UV dosage but with cold shock (2 min after fertilization, 0-4 degrees C for 40 min), the hatching rates were (27.8 +/- 2.1)% and (29.4 +/- 3.3)%, respectively. From hatching to feeding, (15.7 +/- 3.4)% and (23.6 +/- 4.1)% normal gynogenetic diploids were recorded, respectively. Survival of normal gynogenetic diploids was 56% out of the hatched fry when using irradiated spermatozoa of mirror carp, which was lower than that (up to 80%) when using irradiated spermatozoa of blunt snout bream. This indicated that the sperm of blunt snout bream, with distant genetic relation to the maternal Japanese crucian carp, was more effective than that of mirror carp to induce diploid gynogenesis. The nature of the gynogenetic progeny was identified with external appearance, chromosome number and gonad structure. The presence of only females in gynogenetic progeny probably suggested XX genotype in the female Japanese crucian carp. The gynogenetic diploids have potential values such as faster growth and stronger disease resistance than the normal Japanese crucian carp. All gynogenetic progeny possessed 100 chromosomes whereas all J x B crosses were triploid with 124 chromosomes. The formation of the new triploid hybrids in J x B crosses may be useful in aquaculture.

Evidence of different ploidy eggs produced by diploid F2 hybrids of Carassius auratus (female) x Cyprinus carpio (male).

Based on the presence of three types of eggs with different diameters 0.13, 0.17 and 0.2 cm, we made two crosses: F2 (female) x diploid red crucian carp (male), and F2 (female) x F10 tetraploid (male). The ploidy levels of the progeny of the two crosses were examined by chromosome counting and DNA content measurement by flow cytometer. In the offspring of the former cross, tetraploids, triploids, and diploid were obtained. In the progeny of the latter cross, tetraploids and triploids were observed. The production of the different ploidy level fish in the progeny of the two crosses provided a further evidence that F2 might generate triploid, diploid and haploid eggs. The presence of the male tetraploid found in F2 (female) x diploid red crucian carp (male) suggested that the genotype of XXXY probably existed in the tetraploid progeny. The gonadal structures of the tetraploids and triploids indicated that both female and male tetraploids were fertile and the triploids were sterile. We concluded that the formations of different ploidy level eggs from F2 were contributed by endoreduplication and fusion of germ cells.

[Evidence of the unreduced diploid eggs generated from the diploid gynogenetic progeny of allotetraploid hybrids].

Following activation by UV-irradiated sperms from scatter scale common carp and without the treatment for doubling the chromosome number, the eggs generated by the diploid gynogenetic progeny (G1) with 100 chromosomes,developed into diploid gynogenetic progeny (G2) with 100 chromosomes. Both the males and females of the tetraploids with 200 chromosomes were obtained from the offsprings (G1 x AT) produced by mating the eggs of G1 with the diploid sperms from the allotetraploid hybrids. The results provided the evidence that diploid G1 is able to produce diploid eggs. In the oogonia of diploid six-month old G2, only the chromosomes in the metaphase of mitosis were observed in all slides, no bivalent chromosome being found, suggesting that the oogonia in six-month old G2 were not mature enough for meiosis I. The presence of the chromosome spreads with 100, 200 and 380 chromosomes observed in the metaphase indicated that the diploid G2 had the potential ability to generate diploid eggs with the probable mechanism of pre-meiotic endoreduplication. In contrast, the spermatocytes of G1 x AT allotetraploids had the normal chromosomal behavior with only 100 bivalents found in meiosis I. The one-year old G2 possessed the slowly developmental ovaries which stayed at the oogonium stage for a long time, in which no primary and mature oocyte was found, whereas both the females and males of one-year old G1 x AT allotetraploids had normal ovaries and testes which reached maturity and produced diploid eggs and diploid sperms, respectively. The formation of the diploid eggs generated from the diploid gynogenetic progeny makes it available to establish a diploid hybrid clonal line, and will become an important source of production of diploid eggs. In addition, the bisexual fertile G1 x AT allotetraploids enriched the types of the tetraploids.

[Triploid crucain carp-allotetraploid hybrids (male) x goldfish( hermaphrodite)].

A new type of triploid crucian carp was generated by mating the males of the allotetraploid hybrids of red crucian carp (Carassius auratus red var.) (female) x common carp (Cyprinus carpio L.) (male), with the females the goldfish( Carassius auratus red var.) which was red in color and possessed the biforked tails. The biological characteristics of one-year old triploid crucian carp including the number and karotype of chromosome, gonadosomatic indices and gonadal structures, appearance and growth rate were investigated. The results indicated that the triploid crucian carp possessed 150 chromosomes with the karyotype: 33m + 51sm + 33st + 33t. In the breeding season, the gonadosomatic indices (GSI) of the ovaries and testes in the triplpoid crcuian carp were, respectively, lower than those in the diploid red crucian carp, and the tissue sections showed that both the ovaries and the testes in the triploid cruican carp were not able to produce the mature ova and sperm, respectively, indicating that they were sterile during one year. The triploid crucian carp was gray in color and had a single fork tail. They had other morphological traits intermediate to the paternal allotetraploid hybrids and the maternal goldfish, for example, one pair of very short and not readily visible barbells, the formula of lateral line scales: 31-6/7, 18 dorsal fin spines, and 0.5 in ratio of the width to the length of the body which was evidently higher than that (0.41) in another kind of triploid crucian carp called Xiangyun crucian carp, generated by crossing the males of the allotetraploid hybrids with the females of the Japanese crucain carp (Carassius auratus cuvieri T. et S.). Following 8-month culture, the triploid crucian carp averagely reached 350 gram in which the maximum individual weighed 550 gram. Among one- year old triploid crucian carp, the females grew faster than the males. Compared with Xiangyun crucian carp, the new type of triploid crucian carp not only presented some advantages the Xiangyun crucian carp had, for example, fast growth rate and potential sterility, but also got some new good performances like the high ratio of the width to the length of the body and the sweet flesh, suggesting they will be very potential in the commercial interest.

[The chromosome number and gonadal structure of F9-F11 allotetraploid crucian-carp].

In this paper, the chromosome number of F9-F11 hybridis of Red crucian (Carassius auratus) x common carp(Cryprinus carpio) was examined by means of kidney cell-PHA culture. The results showed that F9-F11 allotetraploids possessed 200 chromosomes, with the karyotype formula 44 m + 68 sm + 44 st + 44 t, which were the same as the data indicated in F3-F8 allotetraploids. Both female and male of F9-F11 allotetraploids had the normal ovaries and testes that were able to produce the normal dipoid ova and sperm. In nature conditions, without the injection of the extraneous hormone, the females and males of F9-F11 allotetraploids mated each other to produce new generation of tetraploids. With the stable genetic tetraploidy and the fertility in the nature environments, this allotetraploid population presented the key factors to form a new species with 200 chromosomes.