Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001).

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

Apatinib Inhibits Angiogenesis in Intrahepatic Cholangiocarcinoma by Regulating the Vascular Endothelial Growth Factor Receptor-2/Signal Transducer and Activator of Transcription Factor 3/Hypoxia Inducible Factor 1 Subunit Alpha Signaling Axis.

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC), which is difficult to diagnose and is usually fatal due to its late clinical presentation and a lack of effective treatment, has risen over the past decades but without much improvement in prognosis. OBJECTIVE: The study aimed to investigate the role of apatinib that targets vascular endothelial growth factor receptor-2 (VEGFR2) in ICC. METHODS: MTT assays, cell scratch assays, and tube formation assays were used to assess the effect of apatinib on human ICC cell line (HuCCT-1) and RBE cells proliferation, migration, and angiogenic capacity, respectively. Expression of vascular endothelial growth factor (VEGF), VEGFR2, signal transducer and activator of transcription factor 3 (STAT3), pSTAT3, and hypoxia inducible factor 1 subunit alpha (HIF-1α) pathway proteins was assessed using Western blotting and mRNA expression analysis in HuCCT-1 was performed using RT-qPCR assays. The pcDNA 3.1(-)-VEGFR2 and pcDNA 3.1(-)-HIF-1α were transfected into HuCCT-1 and RBE cells using Lipofectamine 2,000 to obtain overexpressed HuCCT-1 and RBE cells. RESULTS: We found that apatinib-inhibited proliferation, migration, and angiogenesis of HuCCT-1 and RBE cells in vitro in a dose-dependent manner. We also proved that apatinib effectively inhibits angiogenesis in tumor cells by blocking the expression of VEGF and VEGFR2 in these cells. In addition, we demonstrated that apatinib regulates the expression of STAT3 phosphorylation by inhibiting VEGFR2. Finally, we showed that apatinib regulates ICC angiogenesis and HIF-1α/VEGF expression via STAT3. CONCLUSIONS: Based on the above findings, we conclude that apatinib inhibits HuCCT-1 and RBE cell proliferation, migration, and tumor angiogenesis by inhibiting the VEGFR2/STAT3/HIF-1α axis signaling pathway. Apatinib can be a promising drug for ICC-targeted molecular therapy.

Identification of consensus sequence from matrix attachment regions and functional analysis of its activity in stably transfected Chinese hamster ovary cells.

Matrix attachment regions (MARs) can enhance transgene expression levels and maintain stability. However, the consensus sequence from MARs and its functional analysis remains to be examined. Here, we assessed a possible consensus sequence from MARs and assessed its activity in stably transfected Chinese hamster ovary (CHO) cells. First, we analyzed the effects of 10 MARs on transfected CHO cells and then analyzed the consensus motifs from these MARs using a bioinformatics method. The consensus sequence was synthesized and cloned upstream or downstream of the eukaryotic vector. The constructs were transfected into CHO cells and the expression levels and stability of enhanced green fluorescent protein were detected by flow cytometry. The results indicated that eight of the ten MARs increased transgene expression in transfected CHO cells. Three consensus motifs were found after bioinformatics analyses. The consensus sequence tandemly enhanced transgene expression when it was inserted into the eukaryotic expression vector; the effect of the addition upstream was stronger than that downstream. Thus, we found a MAR consensus sequence that may regulate the MAR-mediated increase in transgene expression.

CHRNA5 polymorphisms and risk of lung cancer in Chinese Han smokers.

Lung cancer is the most frequent cancer among men in many countries. It is the result of interactions between genetic and environmental factors, among which tobacco smoking is a key environmental factor. CHRNA5, Cholinergic Receptor, Neuronal Nicotinic, Alpha Polypeptide-5, was previously reported to be associated with lung cancer risk. To identify the genetic susceptibility and tobacco smoking that influence lung cancer risk in Han population, we performed a case-control study in 228 patients and 301 controls. These data were compared using the χ(2)-test, genetic model analysis, and haplotype analysis. rs495956, rs680244, rs601079, rs555018, 588765 and rs11637635 showed an increased risk of lung cancer in both allelic model and genetic mode analysis. The genotype G/A-A/A of rs11637635 was most strongly associated with a 2.17-fold increased risk of lung cancer in dominant model (p = 0.018). One SNP, rs684513, was associated with a 0.645-fold decreased risk (p = 0.033) in allelic model analysis. By haplotype association analysis, haplotype sequences CTTATCAAAGA and GA of CHRNA5 were found to be associated with a 2.03-fold and 1.91-fold increased lung cancer risk (p < 0.05). Our results, combined with those from previous studies, suggest that genetic variation in CHRNA5 may influence susceptibility to lung cancer among Han smokers.

Chinese expert consensus workshop report: Guidelines for thermal ablation of primary and metastatic lung tumors.

Although surgical resection is the primary means of curing both primary and metastatic lung cancers, about 80% of lung cancers cannot be removed by surgery. As most patients with unresectable lung cancer receive only limited benefits from traditional radiotherapy and chemotherapy, many new local treatment methods have emerged, including local ablation therapy. The Minimally Invasive and Comprehensive Treatment of Lung Cancer Branch, Professional Committee of Minimally Invasive Treatment of Cancer of the Chinese Anti-Cancer Association has organized multidisciplinary experts to develop guidelines for this treatment modality. These guidelines aim at standardizing thermal ablation procedures and criteria for selecting treatment candidates and assessing outcomes; and for preventing and managing post-ablation complications.

[Informed consent right of the appraised individuals in forensic clinical examination].

Informed consent right is not just for basic ethical consideration, but is important for protecting patient's right by law, which is expressed through informed consent contract. The appraised individuals of forensic clinical examination have the similar legal status as the patients in medical system. However, the law does not require informed consent right for the appraised individuals. I recommend giving certain informed consent right to the appraised individuals in the forensic clinical examination. Under the contracted relationship with the institution, the appraised individuals could participate in the examination process, know the necessary information, and make a selected consent on the examination results, which can assure the justice and fairness of judicial examination procedure.

Anti-angiogenesis effect of generation 4 polyamidoamine/vascular endothelial growth factor antisense oligodeoxynucleotide on breast cancer in vitro.

OBJECTIVE: To study the effects of the generation 4 polyamidoamine/vascular endothelial growth factor antisense oligodeoxynucleotide (G4PAMAM/VEGFASODN) compound on the expressions of vascular endothelial growth factor (VEGF) and its mRNA of breast cancer cells and on the inhibition of vascular endothelial cells. METHODS: We examined the morphology of G4PAMAM/VEGFASODN compound and its pH stability, in vitro transfection efficiency and toxicity, and the expressions of VEGF and its mRNA. Methyl thiazolyl tetrazolium assay was used to detect the inhibitory function of the compound on vascular endothelial cells. RESULTS: The compound was about 10 nm in diameter and was homogeneously netlike. From pH 5 to 10, it showed quite a buffered ability. The 48-h transfection rate in the charge ratio of 1:40 was 98.76%, significantly higher than that of the liposome group (P<0.05). None of the transfection products showed obvious toxicity on the cells. The expressions of both VEGF protein and its mRNA after G4PAMAM/VEGFASODN transfection decreased markedly. CONCLUSION: With a low toxicity, high safety, and high transfection rate, G4PAMAM/VEGFASODN could be a promising gene vector. Specifically, it inhibits VEGF gene expression efficiently, laying a basis for further in vivo animal studies.

Combined treatment of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer.

AIM: To investigate the efficacy and side effects of the combined therapy of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer (ESCC) and the survival of the patients. METHODS: Sixty-four patients (median age of 63 years) with histological or cytological confirmation of ESCC received oxaliplatin 120 mg/m(2) intravenously on day 1 and capecitabine 1000 mg/m(2) orally twice daily on days 1 to 14 in a 21-d treatment cycle as palliative chemotherapy. Each patient received at least two cycles of treatment. The efficacy, side effects and patient survival were evaluated. RESULTS: The partial response (PR) rate was 43.8% (28/64). Stable disease (SD) rate was 47.9% (26/64), and disease progression rate was 15.6% (10/64). The clinical benefit rate (PR + SD) was 84.4%. The main toxicities were leukopenia (50.0%), nausea and vomiting (51.6%), diarrhea (50.0%), stomatitis (39.1%), polyneuropathy (37.5%) and hand-foot syndrome (37.5%). No grade 4 event in the entire cohort was found. The median progression-free survival was 4 mo, median overall survival was 10 mo (95% CI: 8.3-11.7 mo), and the 1- and 2-year survival rates were 38.1% and 8.2%, respectively. High Karnofsky index, single metastatic lesion and response to the regimen indicated respectively good prognosis. CONCLUSION: Oxaliplatin plus capecitabine regimen is effective and tolerable in metastatic ESCC patients. The regimen has improved the survival moderately and merits further studies.

[Polymorphism of five X-STR loci in Chinese Achang ethnic group].

OBJECTIVE: To investigate the genetic polymorphism and applied value in forensic medicine of five short tandem repeats (STRs) loci(DXS7130, DXS7132, DXS7133, DXS6804 and DXS8378) on X-chromosome in Achang ethnic group. METHODS: Allele frequency and genotype distribution of five X-STR loci among 100 unrelated individuals from Achang ethnic group were analyzed by PCR following polyacrylamide gel electrophoresis and silver staining. Hardy-Weinberg equilibrium of females was tested and forensic parameters were calculated. RESULT: All the five STR loci were polymorphic in Achang ethnic group. Chi-square test indicated that genotype distribution of females was in accordance with Hardy-Weinberg equilibrium. CONCLUSION: These results enrich Chinese genetic database and can be applied to individual identification, paternity testing and population genetics.

[Adverse drug events and its forensic medical identification].

OBJECTIVE: To investigate the basic principles and important rules of forensic identification of adverse drug events and to accumulate basic data and to provide references for forensic identification of similar cases. METHODS: Thirty-three cases of adverse drug events in our forensic identification files were retrospectively reviewed, analyzed, and summarized. RESULTS: There were 27 live and 6 dead victims included in this study. Our study showed a gradually increasing numbers of adverse drug cases in forensic identification year by year with a slight female predominance (20/33 cases, 60.6%). Of the 33 victims, nearly two-thirds (21/33, 63.6%) were due to hospital errors including only one case of drug overdose (1/21, 4.8%), whereas the rest were not related to the hospital errors. Eight cases (8/33, 24.2%) were caused by illegal medical practitioners due to improper use of medication. CONCLUSION: Investigators need to pay more attention to the characteristics and complexities of adverse drug events on a case by case basis encountered in increasing numbers of more and more such forensic identification.

[A debate about mental disability expertise of the disability evaluation criteria of traffic accident injurious].

In recent years, mental disability estimation are more than ever in the practice of forensic psychiatric expertise. The standards about mental disability estimation in the Disability Evaluation Criteria of Traffic Accident Injury are ambiguous and difficult to operate, it cause to different understanding in one case. This article discuss some common questions through 3 aspects in mental disability expertise according to some typical cases, there are the first, we should compare the IQ score before and after injurious in intelligence estimate. The second, the mental disability estimation should be done at least one year after the end of medicine treatment. The third, mental estimate scale should be used in mental disability estimation.

[Genetic polymorphism of DXS7423, DXS7424, DXS7132, DXS7133, DXS6804 loci on X-chromosome in Ewenke population].

OBJECTIVE: To study the genetic polymorphism of five STR loci on X-chromosome in 98 Ewenke population of China and establish the related genetic database. METHODS: The sequence variation of DXS7423, DXS7424, DXS7132, DXS7133, DXS6804 loci on X-chromosome were analyzed by PCR following PAG electrophoresis and silver staining. RESULTS: The genetic data of the 5 X-chromosome STRs in Ewenke ethnic group of China is in accordance with Hard-Weinberg equilibrium. CONCLUSION: Five X-STR loci could be used in forensic identification and population genetic research.

Clinical significance of expression of apoptotic signal proteins in gastric carcinoma tissue.

AIM: To evaluate the expressions of apoptotic signal proteins FADD, TRADD, FasL, Fas, and NFkappaB in gastric carcinoma tissues and their clinical significance. METHODS: Western blot immune trace method was adopted to detect the expressions of apoptotic signal proteins FADD, TRADD, FasL, Fas, and NFkappaB in 55 tissue specimens of gastric carcinoma. RESULTS: Five apoptotic signal proteins had different expressions in the gastric carcinoma samples and their expressions were not correlated to age (P = 0.085). Expressions of the FADD, FasL, Fas, and NFkappaB proteins reduced with increase of the volume of tumor with the exception of increased expression the TRADD protein (64.7-71.1%, P = 0.031). With gradual increase of the malignancy of gastric carcinoma tissues, expressions of the FADD, FasL, and Fas proteins decreased (78.6-28.0%, P = 0.008; 78.6-65.9%, P = 0.071; 100.0-46.3%, P = 0.014), while expressions of the TRADD and NFkappaB proteins increased (42.9-78.1%, P = 0.063; 78.6-79.1%, P = 0.134). With gradual increase of serum CEA, expression of the FADD protein decreased (62.5-34.0%, P = 0.073), but expressions of the TRADD, FasL, Fas, and NFkappaB proteins increased (0.0-80.8%, P = 0.005; 62.5-70.2%, P = 0.093; 0.0-70.2%, P = 0.003; 62.5-80.9%, P = 0.075). When compared to the tissues of gastric carcinoma without metastasis, the positive rate of expressions of the FADD and FasL proteins increased, whereas expressions of the TRADD, FADD, and NFkappaB proteins decreased. There was no significant difference between them (P = 0.095). CONCLUSION: Gastric carcinoma is endurable to Fas-related apoptosis and apoptotic signal proteins are differently expressed in gastric carcinoma.

Alterations of serum cholinesterase in patients with gastric cancer.

AIM: To understand the correlation of serum cholinesterase (CHE) activity with gastric cancer and to assess their clinical significance. METHODS: The velocity method was adopted to detect the activity of serum CHE in patients with gastric cancer and in patients with non-malignant tumor as controls. RESULTS: The serum CHE activity in the treatment group was significantly lower than that in the control group with a very significant difference between the two groups (83.3:113.1,P = 0.0003). Age was significantly associated with the incidence of gastric cancer. CONCLUSION: Serum CHE activity has a close relation with the incidence of gastric cancer.

Allele distribution of five X-chromosome short tandem repeat loci in Ewenke population of north China.

OBJECTIVE: To study the allele genetic polymorphism of five short tandem repeat (STR) loci on X-chromosome in Ewenke population of north China and to provide basic data for forensic identification. METHODS: Genomic DNA was extracted from EDTA-whole blood of Ewenke population by Chelex-100. The DNA samples were amplified by PCR and were analyzed by polyacrylamide gel electrophoresis and silver staining. The sequence length variations of DXS6799, DXS8378, DXS101, HPRTB, and DXS6789 loci on X-chromosome in 98 unrelated Ewenke individuals were investigated. RESULTS: All five loci analyzed showed high polymorphism and genetic stability. The data of the five X-chromosome STR loci in Ewenke ethnic group of China was in accordance with Hardy-Weinberg equilibrium by Chi-square test. CONCLUSION: Allele polymorphism of five X-chromosome STR loci can be used as a genetic marker for forensic identification and population genetic research.

Expression of estrogen receptor and estrogen receptor messenger RNA in gastric carcinoma tissues.

AIM: To study estrogen receptor (ER) and estrogen receptor messenger RNA (ERmRNA) expression in gastric carcinoma tissues and to investigate their association with the pathologic types of gastric carcinoma. METHODS: The expression of ER and ERmRNA in gastric carcinoma tissues (15 males and 15 females, 42-70 years old) was detected by immunohistochemistry and in situ hybridization, respectively. RESULTS: The positive rate of ER (immunohistochemistry) was 33.3 % in males and 46.7 % in females. In Borrmann IV gastric carcinoma ER positive rate was greater than that in other pathologic types, and in poorly differentiated adenocarcinoma and signet ring cell carcinoma the positive rates were greater than those in other histological types of both males and females (P<0.05). The ER was more highly expressed in diffused gastric carcinoma than in non-diffused gastric carcinoma (P<0.05). The ER positive rate was also related to regional lymph nodes metastases (P<0.05), and was significantly higher in females above 55 years old, and higher in males under 55 years old (P<0.05). The ERmRNA (in situ hybridization) positive rate was 73.3 % in males and 86.7 % in females. The ERmRNA positive rates were almost the same in Borrmann I, II, III and IV gastric carcinoma (P>0.05). ERmRNA was expressed in all tubular adenocarcinoma, poorly differentiated adenocarcinoma and signet ring cell carcinoma (P<0.05). The ERmRNA positive rate was related to both regional lymph nodes metastases and gastric carcinoma growth patterns, and was higher in both sexes above 55 years old but without statistical significance (P>0.05). The positive rate of ERmRNA expression by in situ hybridization was higher than that of ER expression by immunohistochemistry (P<0.05). CONCLUSION: ERmRNA expression is related to the pathological behaviors of gastric carcinoma, which might help to predict the prognosis and predict the effectiveness of endocrine therapy for gastric carcinoma.