Worldwide research trends on tumor burden and immunotherapy: a bibliometric analysis.

Various immunotherapy has been greatly applied to comprehensive treatment of malignant cancer under different degrees of tumor burden. Scientific researchers have gained considerable progress in the relationship between immunotherapy and tumor burden in recent years. This review aimed to explore the prospect and developing trends in the field of tumor burden and immunotherapy from a bibliometric perspective. Articles about tumor burden and immunotherapy were collected from the Web of Science Core Collection (WoSCC) (retrieved on 3 January 2023). The R package 'Bibliometrix' analyzed the primary bibliometric features and created a three-filed plot to display the relationship between institutions, countries, and keywords. VOSviewer was used for co-authorship analysis, co-occurrence analysis, and their visualization. And CiteSpace calculated the citation burst references and keywords. A total of 1030 publications were retrieved from 35 years of scientific researches. The United States (US) and China published the most articles. The most productive journals were Cancer Immunology Immunotherapy and Journal for ImmunoTherapy of Cancer . The top one institution of the highest output was University of Texas MD Anderson Cancer Center. The hot keywords of strong citation burst strength in recent years were 'nivolumab', 'tumor microenvironment', and 'immune checkpoint inhibitor'. The most popular tumor type is melanoma. This bibliometric analysis mapped a basic knowledge structure. The field of tumor burden and immunotherapy is entering a rapid growing stage and keeping it value for future research.

Development and validation of web-based nomograms for predicting survival status in patients with intrahepatic cholangiocarcinoma depending on the surgical status: a SEER database analysis.

This study aimed to develop and validate prognostic nomograms that can estimate the probability of 1-, 3- and 5-year overall survival (OS) as well as cancer-specific survival (CSS) for Intrahepatic cholangiocarcinoma (ICCA) patients. Clinical data of 1446 patients diagnosed with ICCA between 2010 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. In both the OS and the CSS group, the training cohort and validation cohort were divided into a 7:3 ratio. Age, sex, AJCC T stage, AJCC N stage, AJCC M stage, surgical status, and tumor grade were selected as independent prognostic risk factors to build the nomograms. To compare the efficacy of predicting 1-, 3-, and 5-year OS and CSS rates of the nomogram with the 8th edition of the American Joint Committee on Cancer (AJCC) staging system, we evaluated the Harrell's index of concordance (C-index), area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) in both cohorts. The results showed the nomogram for 1-, 3-, and 5-year OS and CSS prediction performed better than the AJCC staging system. In the subgroup analysis for patients could not receive surgery as the primary treatment. We developed two nomograms for predicting the 1-, and 2-year OS and CSS rates following the same analysis procedure. Results indicate that the performance of both nomograms, which contained sex, AJCC T stage, AJCC M stage, chemotherapy, and tumor grade and prognostic factors, was also superior to the AJCC staging system. Meanwhile, four dynamic network-based nomograms were published. The survival analysis showed the survival rate of patients classified as high-risk based on the nomogram score was significantly lower compared to those categorized as low-risk (P < 0.0001). Finally, accurate and convenient nomograms were established to assist clinicians in making more personalized prognosis predictions for ICCA patients.

Worldwide productivity and research trend of publications concerning tumor immune microenvironment (TIME): a bibliometric study.

BACKGROUND: As the complexity and diversity of the tumor immune microenvironment (TIME) are becoming better understood, burgeoning research has progressed in this field. However, there is a scarcity of literature specifically focused on the bibliometric analysis of this topic. This study sought to investigate the development pattern of TIME-related research from 2006 to September 14, 2022, from a bibliometric perspective. METHODS: We acquired both articles and reviews related to TIME from the Web of Science Core Collection (WoSCC) (retrieved on September 14, 2022). R package "Bibliometrix" was used to calculate the basic bibliometric features, present the collaborative conditions of countries and authors, and generate a three-field plot to show the relationships among authors, affiliations, and keywords. VOSviewer was utilized for co-authorship analysis of country and institution and keyword co-occurrence analysis. CiteSpace was used for citation burst analysis of keywords and cited references. In addition, Microsoft Office Excel 2019 was used to develop an exponential model to fit the cumulative publication numbers. RESULTS: A total of 2545 publications on TIME were included, and the annual publication trend exhibited a significant increase over time. China and Fudan University were the most productive country and institution, with the highest number of publications of 1495 and 396, respectively. Frontiers in Oncology held the highest number of publications. A number of authors were recognized as the main contributors in this field. The clustering analysis revealed six clusters of keywords that highlighted the research hot spots in the fields of basic medical research, immunotherapy, and various cancer types separately. CONCLUSIONS: This research analyzed 16 years of TIME-related research and sketched out a basic knowledge framework that includes publications, countries, journals, authors, institutions, and keywords. The finding revealed that the current research hot spots of the TIME domain lie in "TIME and cancer prognosis", "cancer immunotherapy", and "immune checkpoint". Our researchers identified the following areas: "immune checkpoint-based immunotherapy", "precise immunotherapy" and "immunocyte pattern", which may emerge as frontiers and focal points in the upcoming years, offering valuable avenues for further exploration.

Clinical response to adding pyrotinib to pembrolizumab and lenvatinib for HER2-positive advanced intrahepatic cholangiocarcinoma: a case report.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly lethal hepatobiliary cancer, and very few patients can undergo surgery. The prognosis of advanced ICC is poor, especially in patients who progress after first-line chemotherapy, with a median overall survival of less than 10 months. CASE PRESENTATION: A 64-year-old male was diagnosed with advanced intrahepatic cholangiocarcinoma with ERBB2 (HER2) 3 + amplification determined by tissue-based testing and confirmed by next-generation sequencing. The patient was treated with pyrotinib added to pembrolizumab and lenvatinib after progressing with pyrotinib and tegafur and responded very well with regression of the tumor on imaging as well as normalization of tumor marker levels without serious adverse events. PET-CT after 6 months of treatment showed a partial response. The progression-free survival with second-line treatment was 17 months. For the third line of therapy, lenvatinib and pembrolizumab were used in combination with bevacizumab. Currently, he has had stable disease for approximately 6 months during third-line treatment. CONCLUSION: Adding pyrotinib to pembrolizumab and lenvatinib may represent a promising strategy for advanced ICC patients who have high levels of HER2.

Clinical outcomes of lenvatinib plus transarterial chemoembolization with or without programmed death receptor-1 inhibitors in unresectable hepatocellular carcinoma.

BACKGROUND: Programmed death receptor-1 (PD-1) inhibitors have been approved as second-line treatment regimen in hepatocellular carcinoma (HCC), but it is still worth studying whether patients can benefit from PD-1 inhibitors as first-line drugs combined with targeted drugs and locoregional therapy. AIM: To estimate the clinical outcome of transarterial chemoembolization (TACE) and lenvatinib plus PD-1 inhibitors for patients with unresectable HCC (uHCC). METHODS: We carried out retrospective research of 65 patients with uHCC who were treated at Peking Union Medical College Hospital from September 2017 to February 2022. 45 patients received the PD-1 inhibitors, lenvatinib, TACE (PD-1-Lenv-T) therapy, and 20 received the lenvatinib, TACE (Lenv-T) therapy. In terms of the dose of lenvatinib, 8 mg was given orally for patients weighing less than 60 kg and 12 mg for those weighing more than 60 kg. Of the patients in the PD-1 inhibitor combination group, 15 received Toripalimab, 14 received Toripalimab, 14 received Camrelizumab, 4 received Pembrolizumab, 9 received Sintilimab, and 2 received Nivolumab, 1 with Tislelizumab. According to the investigators' assessment, TACE was performed every 4-6 wk when the patient had good hepatic function (Child-Pugh class A or B) until disease progression occurred. We evaluated the efficacy by the modified Response Evaluation Criteria in Solid Tumors (mRECIST criteria). We accessd the safety by the National Cancer Institute Common Terminology Criteria for Adverse Events, v 5.0. The key adverse events (AEs) after the initiation of combination therapy were observed. RESULTS: Patients with uHCC who received PD-1-Lenv-T therapy (n = 45) had a clearly longer overall survival than those who underwent Lenv-T therapy (n = 20, 26.8 vs 14.0 mo; P = 0.027). The median progression-free survival time between the two treatment regimens was also measured {11.7 mo [95% confidence interval (CI): 7.7-15.7] in the PD-1-Lenv-T group vs 8.5 mo (95%CI: 3.0-13.9) in the Lenv-T group (P = 0.028)}. The objective response rates of the PD-1-Lenv-T group and Lenv-T group were 44.4% and 20% (P = 0.059) according to the mRECIST criteria, meanwhile the disease control rates were 93.3% and 64.0% (P = 0.003), respectively. The type and frequency of AEs showed little distinction between patients received the two treatment regimens. CONCLUSION: Our results suggest that the early combination of PD-1 inhibitors has manageable toxicity and hopeful efficacy in patients with uHCC.

Primary gastrinoma of the gallbladder: a case report and review of the literature.

Background: Primary gallbladder gastrinoma is an exceptionally uncommon tumor and is a rare form of neuroendocrine neoplasm. Until now, no cases of primary gallbladder gastrinoma and rare cases of primary gastrinoma from the biliary system have been reported. Case presentation: We report a case of a 50-year-old woman with watery diarrhea who intermittently received proton pump inhibitors (PPIs) as treatment. A serum gastrin level of 711 pg/ml was recorded after the withdrawal of PPI over 1 week. Enhanced computed tomography (CT) imaging and octreotide imaging uncovered a solitary tumor at the hepatic hilar region. During the laparoscopic surgery, it was determined that the tumor had its origin in the wall of the gallbladder neck, prompting the implementation of a laparoscopic cholecystectomy. Histological analysis revealed a primary neuroendocrine tumor from the neck of the gallbladder. The patient's symptoms disappeared after the surgery with a follow-up of 6 months. Conclusions: This case confirmed that primary gallbladder gastrinoma represents a distinct nosological entity. Immunohistochemical analysis plays a pivotal role in the diagnostic process. Given the limited understanding of primary gallbladder gastrinoma, our objective is to offer novel insights into this rare disease by delivering distinctive information and highlighting the therapeutic significance of surgical intervention.

Characterization of aroma-active compounds in Dongli by quantitative descriptive analysis, gas chromatography-triple quadrupole tandem mass spectrometry, and gas chromatography-olfactometry.

Dongli, or frozen pear, is a traditional Chinese snack with a unique flavor. This study identified the aroma-active volatile compounds (VOCs) in Dongli using quantitative descriptive analysis (QDA), gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS/MS), and gas chromatography-olfactometry (GC-O). QDA indicated that Dongli of all cultivars presented increased sweet and wine aromas. A total of 21 VOCs were identified by GC-MS/MS. Bidirectional orthogonal partial least square (O2PLS) analysis, GC-O analysis, detection frequency analysis (DFA), and relative odor activity values (ROAV) showed that: estragole and anethole contributing "anise, green" aromas were the key aromatic VOCs of fresh pears, while ethyl butanoate, butyl acetate, heptyl acetate, benzaldehyde, and geranyl acetone contributing "sweet, fruity, green" aromas were the key aromatic VOCs of Dongli. The results revealed that the repeated freezing treatment promoted a unique aroma in pears. This study would contribute to developing new pear products. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05463-8.

Influences of fresh and frozen embryo transfer on neonatal birthweight and the expression of imprinted genes PEG10 /L3MBTL1 in placenta.

To investigate the influences of fresh embryo transfer (ET) and frozen embryo transfer (FET) on neonatal birthweight and the expression of imprinted genes PEG10 and L3MBTL1 in the placenta after in vitro fertilization-embryo transfer (IVF-ET), we analyzed the neonatal birthweight between fresh ET and FET transfer cycles. Then, we collected placentas delivered by fresh ET and FET, and real-time quantitative PCR, Western blotting and immunohistochemistry were used to detect the expression of PEG10 and L3MBTL1. The mean neonatal birthweight of fresh ET was lower than that of FET(3348.48 ± 521.05 vs. 3450.34 ± 524.13, P < 0.001). The risks of low birthweight (LBW) and small-for-gestational age (SGA) were lower after FET (3.9 % vs. 5.4 %; 7.2 % vs. 10.3 %), with adjusted rate ratios of 0.74 (95 % CI, 0.59-0.93; P = 0.003) and 0.70 (95 % CI, 0.59-0.84; P < 0.001), respectively. FET resulted in higher frequencies of macrosomia and large-for-gestational age (LGA) (14.2 % vs. 10.3; 11.0 % vs. 7.1 %) than fresh ET, with adjusted rate ratios of 1.45 (95 % CI, 1.26-1.68; P < 0.001) and 1.62 (95 % CI, 1.37-1.91; P < 0.001), respectively. We also observed PEG10 mRNA and protein expression levels in placentas delivered by fresh ET and FET were significantly different, but there were no significant differences in L3MBTL1 between the two groups. Fresh ET may affect the expression of the imprinted gene PEG10 in the placenta and adverse to placental implantation and development, resulting to increasing incidences of LBW and SGA.

A simultaneous extraction/derivatization strategy coupled with liquid chromatography-tandem mass spectrometry for the determination of free catecholamines in biological fluids.

The current study presents a convenient, rapid and effective simultaneous extraction/derivatization (SEDP) strategy for effective pretreatment of catecholamines (CAs). Commercial zirconium oxide (ZrO2) nanoparticles were employed for the selective capturing of cis-diol containing CAs to remove the biological interferences and phenyl isothiocyanate (PITC) was used for derivatization to improve the ionization and to improve the chromatographic separation. The extraction and derivatization procedures were integrated into one step to simplify the sample pretreatment. Excessive derivatization reagents were removed as well, reducing the degree of contaminations in mass spectrometry. The factors affecting the SEDP process were optimized and the results showed that the detection sensitivity and chromatographic separation of CAs greatly improved compared with underivatized CAs, during LC-MS/MS analysis. Combined with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), quantifying the concentration of norepinephrine (NE), epinephrine (E) and dopamine (DA) in biological fluids was validated in ranges of 1-200.0 ng/mL with a satisfactory correlation coefficient (R2 > 0.997). The obtained recoveries were in the range of 91.0-109.5% with RSDs less than 9.4%. Finally, significant changes in CAs levels in urine samples of healthy people and pheochromocytoma patients were detected. The developed method offers comparative advantages in terms of sensitivity, specificity and selectivity.

Expression and DNA Methylation Status of the Imprinted Genes PEG10 and L3MBTL1 in the Umbilical Cord Blood and Placenta of the Offspring of Assisted Reproductive Technology.

The aim of this study is to investigate the expression and DNA methylation status of the imprinted genes PEG10 and L3MBTL1 in the offspring of assisted reproductive technology (ART). The ART group consists of 30 cases of placenta and umbilical cord blood from ART full-term, uncomplicated singleton pregnancy progeny, and the normal control group consists of 30 cases of placenta and umbilical cord blood from natural full-term, uncomplicated singleton pregnancy progeny. The imprinted genes PEG10 and L3MBTL1 are analyzed, and the expression and methylation status of the two genes are detected using real-time quantitative polymerase chain reaction (QRT-PCR), immunohistochemistry (IHC), Western blotting (WB), and methylation-specific polymerase chain reaction (MSP). Compared with the normal control group, the PEG10 mRNA relative quantity (RQ) value in the placenta is 0.994 ± 0.458, with its RQ value up-regulated (P = 0.015). The PEG10 mRNA RQ value in the umbilical cord blood is 0.875 ± 0.452, with its RQ value up-regulated (P = 0.002). However, the L3MBTL1 mRNA RQ value in the placenta is 0.404 ± 0.234, with its RQ value down-regulated (P = 0.024). The L3MBTL1 mRNA RQ value in the umbilical cord blood is 0.337 ± 0.213, and there is no difference in the umbilical cord blood (P = 0.081). Compared with the normal control group, the expression of PEGl0 protein in the placenta of the ART progeny is up-regulated (P = 0.000), while the expression of L3MBTLl protein is down-regulated (P = 0.000). The methylation status of the PEGl0 promoter region in the placenta in the ART group is lower than that in the normal control group (P = 0.037), and that of the promoter region of the umbilical cord blood is lower than that of the natural pregnancy group (P = 0.032). The methylation status of the L3MBTLl promoter region is higher in the placenta than in the normal control group (P = 0.038), and there is no difference between the two groups in the umbilical cord blood (P = 0.301). In the ART group, the values of PEGl0 and L3MBTLl RQ in the placenta and the umbilical cord blood of the hypermethylated group are lower than in those of the hypomethylated group. ART may increase the risk of the abnormal expression of PEG10 and L3MBTL1 in offspring imprinted genes. The methylation of the promoter region may be the mechanism that regulates the expression of PEGl0 and L3MBTL1.

Air in the biliary duct as an indicator of Type V Mirizzi syndrome: a case report.

Mirizzi syndrome, known as extrinsic bile compression syndrome (EBCS), is difficult to diagnose without surgery. To the best of our knowledge, our case shows that air in the biliary duct may indicate Type V Mirizzi syndrome. A 48-year-old Chinese male, complaining of anorexia with weight loss and jaundice, showed decreased bilirubin for two months after being diagnosed with gallbladder stones. Upon re-examination of the CT, evidence of air in the biliary duct was discovered. Type V EBCS was finally diagnosed during surgery. The patient underwent cholecystectomy, cholecystocolic fistula excision, and Roux-en-Y choledochojejunostomy. The postoperative course was uneventful. Mirizzi's syndrome is a condition which is difficult to diagnose and treat. Air in the biliary duct can be a sign of Type V Mirizzi syndrome, which aids in diagnosis of Type V EBCS before surgery. Cholecystectomy, fistula excision and biliary-enteric anastomosis with Roux-en-Y loop appear to be the most appropriate surgical interventions for the condition.

Clinical utility and effectiveness of a training programme in the application of a new classification of narrow-band imaging for vocal cord leukoplakia: A multicentre study.

OBJECTIVE: To analyse the application of a new narrow-band imaging (NBI) classification in the diagnosis of vocal cord leukoplakia by laryngologists with different levels of laryngoscopic experience and to explore the impact of NBI training programmes on laryngologists' identification of benign and malignant leukoplakia. DESIGN: Prospective multicentre study. SETTING: Tertiary hospitals. PARTICIPANTS: Sixteen laryngologists were divided into less-experienced and experienced groups and received NBI training course. Thirty cases of vocal cord leukoplakia were investigated. MAIN OUTCOME MEASURES: Diagnostic accuracy and interobserver agreement under white light imaging (WLI), before and after NBI training, were analysed among doctors with varying levels of experience. RESULTS: The accuracy in the less-experienced group was significantly lower than that of experience group (0.59 vs 0.69) under WLI. There was no significant difference in the diagnostic accuracy between the less-experienced group and the experienced group before NBI training (0.75 vs 0.74) and after NBI training (0.79 vs 0.83). NBI training could improve the interobserver agreement from fair or moderate to good agreement. CONCLUSION: The new NBI diagnostic classification is helpful for identifying benign and malignant vocal cord leukoplakia. In addition, the NBI training programme can improve the diagnostic accuracy and interobserver agreement of less-experienced doctors to the level of experienced laryngologists.

Optimization of the ultrafiltration-assisted extraction of Chinese yam polysaccharide using response surface methodology and its biological activity.

Ultrafiltration is a separation process for purifying and concentrating macromolecular solutions. Using Baiyu yam (Dioscorea opposita Thunb) as the raw material, single-factor experiments, Box-Behnken design (BBD) and response surface methodology (RSM) were employed to investigate the effects of the ultrafiltration pH, temperature and pressure on the extraction rate of Chinese yam polysaccharide (CYP). The constructed regression model is highly significant, and the optimal ultrafiltration-assisted extraction conditions were determined to be the following: pH 6.5, 20 °C and 0.03 MPa. Under these optimal conditions, a CYP extraction rate of 88.7% was achieved. After purification with anion exchange (DE-52) and size-exclusion (Sephadex G-100) columns, the monosaccharide composition of CYP was determined to be 50.8% glucose, 24.2% mannose and 11.8% galactose. Fourier transform infrared (FT-IR) spectroscopy characterization of CYP confirmed the characteristic absorption peaks of the polysaccharides. The microstructure of CYP exhibited characteristics typical of amorphous powders. CYP also exhibited antioxidant activities, including the scavenging of DPPH radicals, hydroxyl radicals and superoxide anion radicals. Moreover, CYP exhibited a relatively strong inhibitory effect on BGC-823 cell growth.

Erinacine Facilitates the Opening of the Mitochondrial Permeability Transition Pore Through the Inhibition of the PI3K/ Akt/GSK-3ß Signaling Pathway in Human Hepatocellular Carcinoma.

BACKGROUND/AIMS: Erinacine, which is extracted from the medicinal mushroom Hericium erinaceus, is known to play anticancer roles in human cancers. The following study aims to investigate the role of erinacine in the opening of the mitochondrial permeability transition pore (MPTP) in hepatocellular carcinoma (HCC) through the PI3K/Akt/GSK-3ß signaling pathway and highlights the applicability of erinacine in HCC treatments. METHODS: HCC and paracancerous tissues were obtained from 85 HCC patients who've undergone surgical resection. Immunohistochemistry was adopted to detect positive expression of PI3K, Akt, and GSK-3ß. Treatment of HepG-2 with LY294002 (an inhibitor of the PI3K/Akt/GSK-3ß signaling pathway) and different concentration of erinacine was performed to determine the involvement of LY294002 in erinacine action. The expressions of PI3K, Akt, GSK-3ß, CyclinD1, Vimentin, ß-catenin, Bcl-2, E-cadherin, Bax, and caspase-9 were determined by RT-qPCR and Western blot analysis. Cell viability, colony formation rate, migration, invasion, cycle, and apoptosis were detected by MTT, colony formation, wound healing assay, Transwell assay, and flow cytometry, respectively. The size and weight of xenograft tumors were observed in nude mice. Mitochondrial membrane potential in HepG-2 was determined using laser scanning confocal microscopy following JC-1 staining. Mitochondrial Ca2+ indicator Rhod-2, AM was used to detect the changes of mitochondrial Ca2+, while western blot analysis was employed to detect the presence levels of cytochrome C (cyt-C). RESULTS: The results revealed that PI3K, Akt, and GSK-3ß were up-regulated in HCC tissues. Erinacine or LY294002 led to a decrease in mitochondrial membrane potential, increase in intracellular mitochondrial Ca2+, and the release of cyt-C in mitochondria. In addition, Erinacine was found to decrease the mitochondrial membrane potential, expression of PI3K, Akt, GSK-3ß, CyclinD1, Vimentin, ß-catenin, and Bcl-2, cell proliferation, colony formation ability, migration, invasion, and xenograft tumor size, while E-cadherin, Bax, and caspase-9 expression, and cell apoptosis were elevated in a dose-dependent manner. Erinacine also stimulated the effects of LY294002 on the HCC. Following the addition of 500 µM Erinacine and MPTP opening inhibitor CsA, we found that the mitochondrial membrane potential level increased, while mitochondrial Ca2+ and Cyt-C decreased from the mitochondria. CONCLUSION: The results from the study demonstrated that erinacine induced MPTP opening, facilitates the release of cyt-C, and inhibited cell proliferation, migration, and invasion, while it promotes apoptosis by inactivating the PI3K/Akt/GSK-3ß signaling pathway, preventing the progression of HCC.