Microwave synthesized novel biomass carbon dots applied in the fluorescent detection of crystal violet.

To establish a new method for detecting crystal violet (CV), a harmful dye, herein, a genre of novel biomass carbon dots (CDs) was synthesized via a microwave method and employed as a fluorescent probe, in which water spinach and polyethylene glycol (PEG) performed as raw materials. Based on the inner filter effect (IFE) between the luminescent CDs and CV, the blue emission of this probe at 430 nm could be quenched by CV. Hence, a new strategy was proposed to selectively determine CV in aquaculture ambient. Moreover, under the optimal experiment conditions, this method showed a good linearity between the concentration of CV (c) and fluorescence quenching rate (ΔF/F0) in the concentration range of 4-200 µmol/L with the corresponding correlation coefficient (r) and the detection limit of 0.997 and 710 nmol/L, respectively. With advantages of environmental protectivity, sensitivity, affordability, and user-friendliness, the facilely fabricated CDs could be successfully applied in detecting CV in aquaculture samples, providing a technical foundation for monitoring the pollution of CV and ensuring the quality and safety of aquatic products.

Risk predictive model based on three immune-related gene pairs to assess prognosis and therapeutic sensitivity for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) as a common tumor has a poor prognosis. Recently, a combination of atezolizumab and bevacizumab has been recommended as the preferred regimen for advanced HCC. However, the overall response rate of this therapy is low. There is an urgent need to identify sensitive individuals for this precise therapy among HCC patients. METHODS: The Wilcox test was used to screen the differentially expressed immune-related genes by combining the TCGA cohort and the Immunology Database. Univariate and multivariate Cox regression analysis were used to screen the immune gene pairs concerning prognosis. A predictive model was constructed using LASSO Cox regression analysis, and correlation analysis was conducted between the signature and clinical characteristics. ICGC cohort and GSE14520 were applied for external validations of the predictive risk model. The relationship between immune cell infiltration, TMB, MSI, therapeutic sensitivity of immune checkpoint inhibitors, targeted drugs, and the risk model were assessed by bioinformatics analysis in HCC patients. RESULTS: A risk predictive model consisting of 3 immune-related gene pairs was constructed and the risk score was proved as an independent prognostic factor for HCC patients combining the TCGA cohort. This predictive model exhibited a positive correlation with tumor size (p < 0.01) and tumor stage (TNM) (p < 0.001) in the chi-square test. The predictive power was verified by external validations (ICGC and GSE14520). The risk score clearly correlated with immune cell infiltration, MSI, immune checkpoints, and markers of angiogenesis. CONCLUSIONS: Our research established a risk predictive model based on 3 immune-related gene pairs and explored its relationship with immune characteristics, which might help to assess the prognosis and treatment sensitivity to immune and targeted therapy of HCC patients.

[Metabolic engineering study on biosynthesis of 4-hydroxybenzyl alcohol from L-tyrosine in Escherichia coli].

As an important active ingredient in the rare Chinese herb Gastrodiae Rhizoma and also the main precursor for gastrodin biosynthesis, 4-hydroxybenzyl alcohol has multiple pharmacological activities such as anti-inflammation, anti-tumor, and anti-cerebral ischemia. The pharmaceutical products with 4-hydroxybenzyl alcohol as the main component have been increasingly favored. At present, 4-hydroxybenzyl alcohol is mainly obtained by natural extraction and chemical synthesis, both of which, however, exhibit some shortcomings that limit the long-term application of 4-hydroxybenzyl alcohol. The wild and cultivated Gastrodia elata resources are limited. The chemical synthesis requires many steps, long time, and harsh reaction conditions. Besides, the resulting by-products are massive and three reaction wastes are difficult to treat. Therefore, how to artificially prepare 4-hydroxybenzyl alcohol with high yield and purity has become an urgent problem facing the medical researchers. Guided by the theory of microbial metabolic engineering, this study employed the genetic engineering technologies to introduce three genes ThiH, pchF and pchC into Escherichia coli for synthesizing 4-hydroxybenzyl alcohol with L-tyrosine. And the fermentation conditions of engineering strain for producing 4-hydroxybenzyl alcohol in shake flask were also discussed. The experimental results showed that under the conditions of 0.5 mmol·L~(-1) IPTG, 15 ℃ induction temperature, and 40 ℃ transformation temperature, M9 Y medium containing 200 mg·L~(-1) L-tyrosine could be transformed into(69±5)mg·L~(-1) 4-hydroxybenzyl alcohol, which has laid a foundation for producing 4-hydroxybenzyl alcohol economically and efficiently by further expanding the fermentation scale in the future.

Effect of Nucleos(t)ide Analogs on Patients with Intermediate and Advanced Hepatitis B Virus-Related Hepatocellular Carcinoma.

BACKGROUND: The role of nucleos(t)ide analogs (NAs) therapy in intermediate and advanced hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unclear. AIMS: The aim was to evaluate the effect of NAs therapy on survival of intermediate- and advanced-stage HBV-related HCC patients initially treated with chemoembolization. METHODS: A total of 1016 Barcelona Clinic Liver Cancer (BCLC) stage B/C HBV-related HCC patients initially treated with chemoembolization were included. Propensity score matching (PSM) was performed to decrease heterogeneity between the antiviral and non-antiviral groups. Kaplan-Meier and Cox regression analysis were performed to evaluate the effects of NAs therapy on overall survival (OS). RESULTS: Antiviral group (n = 394) significantly prolonged OS compared with non-antiviral group (n = 622) (p = 0.003). NAs therapy (p < 0.001) along with tumor size (p = 0.002), tumor number (p = 0.001), gross vascular invasion (p < 0.001), metastasis (p < 0.001), α-fetoprotein (p < 0.001), Child-Pugh score (p = 0.008), aspartate aminotransferase (p < 0.001), and HBV DNA (p = 0.018) were identified as independent prognostic factors for OS. After PSM processing, deducting the influence of subsequent treatments for HCC, NAs therapy was still identified as an independent protective factor (p = 0.009) for OS in patients who survived ≥ 7 months, regardless of BCLC stage B or C HCC. CONCLUSION: NAs therapy prolongs OS in intermediate- and advanced-stage HBV-related HCC patients initially treated with chemoembolization. After PSM processing, patients who survived ≥ 7 months still benefited from NAs therapy.

Bifunctional bisphosphonate derivatives and platinum complexes with high affinity for bone hydroxyapatite.

A series of ethylenediamine/1,3-propanediamine derivatives containing bifunctional bisphosphonate substituents and their corresponding dichloroplatinum(II) complexes have been synthesized and characterized by elemental analysis, 1H NMR, 13C NMR, 31P NMR, and HRMS spectra. Based on WST-8 assay with CCK-8, in general, the newly synthesized dichloroplatinum complexes 1-6 showed higher in vitro antitumor activity than platinum-free compounds L1-L6 against three tumor cell lines (especially osteosarcoma MG-63). According to hydroxyapatite binding experiment, complexes 2, 3, and 6 showed much higher affinity (K'=3.7, 4.0, and 3.0, respectively) for bone hydroxyapatite than cisplatin (K'<0.1), comparable to zoledronate (K'=2.8). It can be found that representative complex 2 with high cytotoxicity and in vitro antiproliferative activity against osteosarcoma cell line, as well as promising hydroxyapatite binding ability has been screened as a potential bone-targeting antitumor agent for subsequent in vivo study. In addition, flow cytometry experiment was applied to investigate the mode of action of representative complex 2.

Efficacy of Augmented Reality Combined with Indocyanine Green Fluorescence Imaging Guided Laparoscopic Segmentectomy for Hepatocellular Carcinoma.

BACKGROUND: The internal anatomy of the liver is extremely complex. Laparoscopic anatomical segmentectomy requires reference to the position and alignment of intrahepatic vascular. However, the surface of the liver lacks anatomical landmarks and the liver segment boundaries cannot be identified with the naked eye. Augmented reality navigation (ARN) and indocyanine green fluorescence imaging (FI) are emerging navigation tools in liver resection. This study aimed to explore the efficacy and application value of laparoscopic anatomical segmentectomy guided by ARN combined with indocyanine green FI. STUDY DESIGN: Ninety-eight patients who were diagnosed with hepatocellular carcinoma and underwent laparoscopic anatomical segmentectomy from January 2018 to January 2022 were retrospectively analyzed. They were divided into the ARN-FI group (45 patients) and the non-ARN-FI group (53 patients) based on whether ARN combined with FI was applied during the operation. The differences in intraoperative and postoperative outcomes were compared. RESULTS: There was no significant difference in preoperative baseline data and postoperative complication rates between the 2 groups. Compared with the non-ARN-FI group, the ARN-FI group had much lower intraoperative blood loss (100 vs 200 mL, p = 0.005) and a lower incidence of remnant liver ischemia (13.3% vs 30.2%, p = 0.046). The 1- and 3-year disease-free survival rates in the ARN-FI and non-ARN-FI groups were 91.01% vs 71.15% and 70.01% vs 52.46%, respectively; the differences between the 2 groups were statistically significant (p = 0.047). CONCLUSIONS: The ARN-FI technology provides a more standardized approach for liver parenchyma section during laparoscopic liver resection, effectively minimizing intraoperative blood loss, reducing postoperative remnant liver ischemia, and improving oncological prognosis. This method is safe and feasible and has good clinical application prospects.

Analysis of the Short-Term Complications of Laparoscopic Pancreaticoduodenectomy in Patients with Metabolic Syndrome.

Objective: To investigate the impact of metabolic syndrome (MetS) on short-term complications of laparoscopic pancreaticoduodenectomy (LPD). Materials and Methods: We retrospectively analyzed perioperative data of patients who underwent LPD in our department from January 2020 to January 2022. The patients were divided into the MetS group and non-MetS group based on whether they had MetS. The incidence of postoperative complications and mortality rate was compared between the two groups. Results: The study involved 279 patients, with 30 having MetS and 249 without. However, the MetS and non-MetS groups differed significantly in terms of postoperative pancreatic fistula rate (26.6% versus 8.4%), abdominal infection rate (33.3% versus 10.0%), pulmonary complications rate (16.7% versus 6.42%), Clavien-Dindo ≥3 rate (20% versus 8.0%), multiple complications rate (23.3% versus 9.6%), percutaneous drainage rate (33.3% versus 10.0%), 90-day mortality rate (6.7% versus 1.2%), and length of postoperative hospital stay (15.00 ± 12.78 versus 10.63 ± 5.23 days). However, the two groups differed no significantly with respect to age, gender, American Society of Anesthesiologists score, preoperative CA125/CA199 levels, surgery time, specimen removal time, and intraoperative blood loss. Conclusion: MetS increases the incidence of postoperative complications and perioperative mortality rate in LPD.

Cuproptosis-related lncRNAs potentially predict prognosis and therapy sensitivity of breast cancer.

Background: Cuproptosis-related lncRNAs regulate the biological functions of various cancers. However, the role of cuproptosis-related lncRNAs in breast cancer remains unclear. In this study, we investigated the biological functions and clinical applications of cuproptosis-related lncRNAs in breast cancer. Methods: The Cancer Genome Atlas (TCGA) database and the GSE20685 dataset were used for screening cuproptosis-related lncRNAs. Colony formation and CCK-8 kit assays were performed for detecting the proliferative function of cuproptosis-related lncRNAs, whereas wound healing, migration, and invasion assays were performed for detecting the metastatic regulation of cuproptosis-related lncRNAs in breast cancer. Finally, a prognostic cuproptosis-related lncRNA model was constructed using LASSO Cox regression analysis for detecting survival and sensitivity to conventional treatment (endocrine therapy, chemotherapy, and radiotherapy) and novel therapy (PARP and CDK4/6 inhibitors). Results: In this study, we screened six cuproptosis-related lncRNAs associated with the survival of patients with breast cancer. Biofunctional experiments indicated that cuproptosis-related lncRNAs play essential roles in regulating the proliferation and metastasis of breast cancer cells. Finally, we applied a model of six cuproptosis-related lncRNAs to classify the patients into high- and low-risk groups. High-risk group patients exhibited worse survival rates (p < 0.001) and lower sensitivity to chemotherapy, endocrine therapy, and radiation therapy. Compared with high-risk patients, low-risk patients exhibited a lower expression of CDK4/6 inhibitor-resistant biomarkers (CCNE1, E2F1, and E2F2) and PARP inhibitor-resistant biomarkers (BRCA1/BRCA2), indicating that patients in the low-risk group were more suitable for PARP inhibitor and CDK4/6 inhibitor application. Conclusion: Cuproptosis-related lncRNAs are essential for regulating the biological functions of breast cancer, and they have the potential to predict prognosis and sensitivity of breast cancer to various therapies.

Monkeypox Knowledge Investigation and Knowledge Gap Analysis: An Online Cross-Sectional Survey in China.

Background: Monkeypox, as a significant public health concern, warrants a thorough investigation into public knowledge and understanding. Especially in non-endemic areas like China, exploring the factors contributing to knowledge and understanding gaps is crucial for effective disease management and prevention strategies. Objective: This study aims to assess the level of monkeypox knowledge among the Chinese public and to identify the factors that influence this knowledge, particularly focusing on the knowledge gaps between different educational groups. Methods: An online cross-sectional survey was conducted involving 720 participants stratified by age, between July and August 2023. The survey used a modified monkeypox knowledge questionnaire, and hierarchical regression analysis was employed to analyze the data. Results: The study revealed a significant knowledge gap in the understanding of monkeypox among the Chinese public. Key factors influencing this knowledge included educational level, perceived relevance of information, interpersonal communication, and exposure to social media and official health websites. Notably, exposure to social media was found to widen the knowledge gap between different educational groups, with its positive impact more pronounced in individuals with at least a junior high school education. Conclusion: The findings emphasize the need for varied communication strategies to effectively disseminate information about monkeypox and bridge the existing knowledge gaps. Tailoring health communication to different educational levels and utilizing diverse information sources are crucial for improving public understanding and containment of monkeypox.

Green and rapid synthesis of biomass carbon dot-based fluorescence sensing for the sensitive determination of oxytetracycline.

Eco-friendly biomass carbon dots (CDs) with blue fluorescence emission were rapidly synthesized by a microwave method. Based on the inner filter effect (IFE) between oxytetracycline (OTC) and CDs, the fluorescence of CDs could be selectively quenched by OTC. Therefore, a simple and time-saving fluorescence sensing system for the detection of OTC was established. Under optimal experimental conditions, the concentration of OTC showed a good linear relationship with fluorescence quenching values (ΔF) in the range of 4.0-100.0 µmol L-1, a corresponding correlation coefficient (r) of 0.9975, and a detection limit of 0.12 µmol L-1. The method has the advantages of low cost, time-saving, and green synthesis that could be used for the determination of OTC. Moreover, possessing high sensitivity and specificity, this fluorescence sensing method was successfully applied for detecting OTC in milk, indicating its potential applications in food safety.

Augmented reality-assisted navigation system contributes to better intraoperative and short-time outcomes of laparoscopic pancreaticoduodenectomy: a retrospective cohort study.

BACKGROUND: Augmented reality (AR)-assisted navigation system are currently good techniques for hepatectomy; however, its application and efficacy for laparoscopic pancreatoduodenectomy have not been reported. This study sought to focus on and evaluate the advantages of laparoscopic pancreatoduodenectomy guided by the AR-assisted navigation system in intraoperative and short-time outcomes. METHODS: Eighty-two patients who underwent laparoscopic pancreatoduodenectomy from January 2018 to May 2022 were enrolled and divided into the AR and non-AR groups. Clinical baseline features, operation time, intraoperative blood loss, blood transfusion rate, perioperative complications, and mortality were analyzed. RESULTS: AR-guided laparoscopic pancreaticoduodenectomy was performed in the AR group ( n =41), whereas laparoscopic pancreatoduodenectomy was carried out routinely in the non-AR group ( n =41). There was no significant difference in baseline data between the two groups ( P >0.05); Although the operation time of the AR group was longer than that of the non-AR group (420.15±94.38 vs. 348.98±76.15, P <0.001), the AR group had a less intraoperative blood loss (219.51±167.03 vs. 312.20±195.51, P =0.023), lower blood transfusion rate (24.4 vs. 65.9%, P <0.001), lower occurrence rates of postoperative pancreatic fistula (12.2 vs. 46.3%, P =0.002) and bile leakage (0 vs. 14.6%, P =0.026), and shorter postoperative hospital stay (11.29±2.78 vs. 20.04±11.22, P <0.001) compared with the non-AR group. CONCLUSION: AR-guided laparoscopic pancreatoduodenectomy has significant advantages in identifying important vascular structures, minimizing intraoperative damage, and reducing postoperative complications, suggesting that it is a safe, feasible method with a bright future in the clinical setting.

A novel nomogram based on preoperative parameters to predict posthepatectomy liver failure in patients with hepatocellular carcinoma.

BACKGROUND: Posthepatectomy liver failure is one of the main causes of death in patients after hepatectomy. This study intends to establish a prediction model to predict the risk of posthepatectomy liver failure and provide a scientific basis for further reducing the incidence of posthepatectomy liver failure. METHODS: This was a retrospective analysis of 1,172 patients with hepatocellular carcinoma undergoing partial hepatectomy. Using univariate and multivariate logistic regression analyses and stepwise regression, a prediction model for posthepatectomy liver failure was established based on the independent risk factors for posthepatectomy liver failure and validated by bootstrapping with 100 resamples, and the receiver operating characteristic curve was used to evaluate the predictive value of the prediction model. RESULTS: The incidence rate of posthepatectomy liver failure was 22.7% (266/1172). The results showed that the indocyanine green retention rate at 15 minutes (odds ratio = 1.05, P = .002), alanine transaminase (odds ratio = 1.02, P < .001), albumin rate (odds ratio = 0.92, P < .001), total bilirubin (odds ratio = 1.04, P < .001), prothrombin time (odds ratio = 2.44, P < .001), aspartate aminotransferase-neutrophil ratio (odds ratio = 0.95, P < .001), and liver fibrosis index (odds ratio = 1.35, P < .001) were associated with posthepatectomy liver failure. These 7 independent risk factors for posthepatectomy liver failure were integrated into a nomogram prediction model, the predictive efficiency for posthepatectomy liver failure (area under the curve = 0.818, 95% confidence interval 0.789-0.848) was significantly higher than in other predictive models with a liver fibrosis index (area under the curve = 0.651), indocyanine green R15 (area under the curve = 0.669), albumin-bilirubin score (area under the curve = 0.709), albumin-indocyanine green evaluation score (area under the curve = 0.706), model for end-stage liver disease score (area under the curve = 0.636), and Child‒Pugh (area under the curve = 0.551) (all P < .001). The risk of posthepatectomy liver failure in the high-risk posthepatectomy liver failure group (score ≥152) was higher than that in the posthepatectomy liver failure low-risk group (score <152). CONCLUSION: This study developed and validated a nomogram model to predict the risk of posthepatectomy liver failure before surgery that can effectively predict the risk of posthepatectomy liver failure in patients with hepatocellular carcinoma.

Factors influencing the surveillance of re-emerging intracranial infections in elective neurosurgical patients: A single-center retrospective study.

BACKGROUND: At present, many studies have reported the risk factors for postoperative intracranial reinfection, including age, sex, time to surgery, duration of postoperative catheterization, emergency procedures, type of disease and cerebrospinal fluid leakage, but the academic community has not reached a unified conclusion. AIM: To find factors influencing the surveillance of re-emerging intracranial infections in elective neurosurgical patients. METHODS: Ninety-four patients who underwent elective craniotomy from January 1, 2015 to December 31, 2022 in the Department of Neurosurgery, First Hospital of Jilin University, were included in this study. Of those, 45 patients were enrolled in the infection group, and 49 were enrolled in the control group. The clinical data of the patients were collected and divided into three categories, including preoperative baseline conditions, intraoperative characteristics and postoperative infection prevention. The data were analyzed using SPSS 26.0 software. RESULTS: There were 23 males and 22 females in the infection group with a mean age of 52.8 ± 15.1 years and 17 males and 32 females in the control group with a mean age of 48.9 ± 15.2 years. The univariate analysis showed that the infection group had higher systolic blood pressures and postoperative temperatures, fewer patients who underwent a supratentorial craniotomy, more patients with a history of hypertension and higher initial postoperative white blood cell counts than the control group, with statistically significant differences (P < 0.05). The multifactorial logistic regression analysis showed that a history of hypertension and a high postoperative body temperature were independent risk factors for postoperative infection in neurosurgical patients. CONCLUSION: The results obtained in this study indicated that a history of hypertension and a high postoperative body temperature were independent risk factors for postoperative neurological symptoms.

Hepatitis B virus-related intrahepatic cholangiocarcinoma originates from hepatocytes.

BACKGROUND: Hepatitis B virus (HBV) infection is one of the most common risk factors for intrahepatic cholangiocarcinoma (ICC). However, there is no direct evidence of a causal relationship between HBV infection and ICC. In this study, we attempted to prove that ICC may originate from hepatocytes through a pathological study involving ICC tissue-derived organoids. METHOD: The medical records and tumor tissue samples of 182 patients with ICC after hepatectomy were collected. The medical records of 182 patients with ICC were retrospectively analyzed to explore the prognostic factors. A microarray of 182 cases of ICC tumor tissue and 6 cases of normal liver tissue was made, and HBsAg was stained by immunohistochemistry (IHC) to explore the factors closely related to HBV infection. Fresh ICC tissues and corresponding adjacent tissues were collected to make paraffin sections and organoids. Immunofluorescence (IF) staining of factors including HBsAg, CK19, CK7, Hep-Par1 and Albumin (ALB) was performed on both fresh tissues and organoids. In addition, we collected adjacent nontumor tissues of 6 patients with HBV (+) ICC, from which biliary duct tissue and normal liver tissue were isolated and RNA was extracted respectively for quantitative PCR assay. In addition, the expression of HBV-DNA in organoid culture medium was detected by quantitative PCR and PCR electrophoresis. RESULTS: A total of 74 of 182 ICC patients were HBsAg positive (40.66%, 74/182). The disease-free survival (DFS) rate of HBsAg (+) ICC patients was significantly lower than that of HBsAg (-) ICC patients (p = 0.0137). IF and IHC showed that HBsAg staining was only visible in HBV (+) ICC fresh tissues and organoids, HBsAg expression was negative in bile duct cells in the portal area. Quantitative PCR assay has shown that the expression of HBs antigen and HBx in normal hepatocytes were significantly higher than that in bile duct epithelial cells. Combined with the IF and IHC staining, it was confirmed that HBV does not infect normal bile duct epithelial cells. In addition, IF also showed that the staining of bile duct markers CK19 and CK7 were only visible in ICC fresh tissue and organoids, and the staining of hepatocyte markers Hep-Par1 and ALB was only visible in normal liver tissue fresh tissue. Real-time PCR and WB had the same results. High levels of HBV-DNA were detected in the culture medium of HBV (+) organoids but not in the culture medium of HBV (-) organoids. CONCLUSION: HBV-related ICC might be derived from hepatocytes. HBV (+) ICC patients had shorter DFS than HBV (-) ICC patients.

Metatranscriptomics Reveals the RNA Virome of Ixodes Persulcatus in the China-North Korea Border, 2017.

In recent years, numerous viruses have been identified from ticks, and some have been linked to clinical cases of emerging tick-borne diseases. Chinese northeast frontier is tick infested. However, there is a notable lack of systematic monitoring efforts to assess the viral composition in the area, leaving the ecological landscape of viruses carried by ticks not clear enough. Between April and June 2017, 7101 ticks were collected to perform virus surveillance on the China-North Korea border, specifically in Tonghua, Baishan, and Yanbian. A total of 2127 Ixodes persulcatus were identified. Further investigation revealed the diversity of tick-borne viruses by transcriptome sequencing of Ixodes persulcatus. All ticks tested negative for tick-borne encephalitis virus. Transcriptome sequencing expanded 121 genomic sequence data of 12 different virus species from Ixodes persulcatus. Notably, a new segmented flavivirus, named Baishan Forest Tick Virus, were identified, closely related to Alongshan virus and Harz mountain virus. Therefore, this new virus may pose a potential threat to humans. Furthermore, the study revealed the existence of seven emerging tick-borne viruses dating back to 2017. These previously identified viruses included Mudanjiang phlebovirus, Onega tick phlebovirus, Sara tick phlebovirus, Yichun mivirus, and three unnamed viruses (one belonging to the Peribunyaviridae family and the other two belonging to the Phenuiviridae family). The existence of these emerging tick-borne viruses in tick samples collected in 2017 suggests that their history may extend further than previously recognized. This study provides invaluable insights into the virome of Ixodes persulcatus in the China-North Korea border region, enhancing our ongoing efforts to manage the risks associated with tick-borne viruses.

Preliminary Exploration on the Efficacy of Augmented Reality-Guided Hepatectomy for Hepatolithiasis.

BACKGROUND: The augmented reality-assisted navigation system (AR-ANS) has been initially applied to the management of hepatolithiasis. The current study examines the safety and efficacy of the AR-ANS for hepatectomy in the treatment of hepatolithiasis. It is the first study to assess the preoperative and long-term outcomes of hepatectomy guided by the AR-ANS for hepatolithiasis. STUDY DESIGN: From January 2018 to December 2021, 77 patients with hepatolithiasis who underwent hepatectomy at Zhujiang Hospital of Southern Medical University were included. The subjects were divided into the AR group (n = 31) and the non-AR group (n = 46) according to whether the surgery was guided by the AR-ANS. Clinical baseline features, operation time, intraoperative blood loss, immediate postoperative residual stone rate, postoperative stone recurrence rate at 6 months, and postoperative complications were analyzed. RESULTS: There was no significant difference between preoperative baseline data from the 2 groups (p > 0.05). The AR group had a longer surgical time than the non-AR group (p < 0.001). The intraoperative blood loss in the AR group was lower than in the non-AR group (p < 0.001). Alanine transaminase, aminotransferase, immediate residual stone rate, and stone recurrence rate in the AR group were lower than in the non-AR group (p < 0.05). There was no significant difference in postoperative complications between the 2 groups. CONCLUSIONS: The application of the AR-ANS in hepatectomy for hepatolithiasis has not only achieved satisfactory therapeutic efficacy, but has also shown significant advantages in reducing intraoperative blood loss, immediate stone residual rate, and stone recurrence rate, which has clinical promotion value.

Six Metabolism Related mRNAs Predict the Prognosis of Patients With Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common aggressive solid malignant tumors and current research regards HCC as a type of metabolic disease. This study aims to establish a metabolism-related mRNA signature model for risk assessment and prognosis prediction in HCC patients. Methods: HCC data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Enrichment Analysis (GSEA) website. Least absolute shrinkage and selection operator (LASSO) was used to screen out the candidate mRNAs and calculate the risk coefficient to establish the prognosis model. A high-risk group and low-risk group were separated for further study depending on their median risk score. The reliability of the prediction was evaluated in the validation cohort and the whole cohort. Results: A total of 548 differential mRNAs were identified from HCC samples (n = 374) and normal controls (n = 50), 45 of which were correlated with prognosis. A total of 373 samples met the screening criteria and there were randomly divided into the training cohort (n = 186) and the validation cohort (n = 187). In the training cohort, six metabolism-related mRNAs were used to construct a prognostic model with a LASSO regression model. Based on the risk model, the overall survival rate of the high-risk cohort was significantly lower than that of the low-risk cohort. The results of a time-ROC curve proved that the risk score (AUC = 0.849) had a higher prognostic value than the pathological grade, clinical stage, age or gender. Conclusion: The model constructed by the six metabolism-related mRNAs has a significant value for survival prediction and can be applied to guide the evaluation of HCC and the designation of clinical therapy.

Oncogenic PAX6 elicits CDK4/6 inhibitor resistance by epigenetically inactivating the LATS2-Hippo signaling pathway.

Intrinsic resistance to CDK4/6 inhibitors hinders their clinical utility in cancer treatment. Furthermore, the predictive markers of CDK4/6 inhibitors in gastric cancer (GC) remain incompletely described. Here, we found that PAX6 expression was negatively correlated with the response to palbociclib in vitro and in vivo in GC. We observed that the PAX6 expression level was negatively correlated with the overall survival of GC patients and further showed that PAX6 can promote GC cell proliferation and the cell cycle. The cell cycle is regulated by the interaction of cyclins with their partner serine/threonine cyclin-dependent kinases (CDKs), and the G1/S-phase transition is the main target of CDK4/6 inhibitors. Therefore, we tested whether PAX6 expression was correlated with the GC response to palbociclib. We found that PAX6 hypermethylates the promoter of LATS2 and inactivates the Hippo pathway, which upregulates cyclin D1 (CCND1) expression. This results in a suppressed response to palbociclib in GC. Furthermore, we found that the induction of the Hippo signaling pathway or treatment with a DNA methylation inhibitor could overcome PAX6-induced palbociclib resistance in GC. These findings uncover a tumor promoter function of PAX6 in GC and establish overexpressed PAX6 as a mechanism of resistance to palbociclib.

Four Immune-Related Long Non-coding RNAs for Prognosis Prediction in Patients With Hepatocellular Carcinoma.

BACKGROUND: Long non-coding RNA (LncRNA) plays an important role in the occurrence and development of hepatocellular carcinoma (HCC). This study aims to establish an immune-related LncRNA model for risk assessment and prognosis prediction in HCC patients. METHODS: Hepatocellular carcinoma patient samples with complete clinical data and corresponding whole transcriptome expression were obtained from the Cancer Genome Atlas (TCGA). Immune-related genes were acquired from the Gene Set Enrichment Analysis (GSEA) website and matched with LncRNA in the TCGA to get immune-related LncRNA. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for screening the candidate LncRNAs and calculating the risk coefficient to establish the prognosis model. Patients were divided into a high-risk group and a low-risk group depending on the median risk score. The reliability of the prediction was evaluated in the validation cohort and the whole cohort. GSEA and principal component analysis were used for function evaluation. RESULTS: A total of 319 samples met the screening criteria and were randomly distributed across the training cohort and the validation cohort. After comparison with the IMMUNE_RESPONSE gene set and the IMMUNE_SYSTEM_PROCESS gene set, a total of 3094 immune-related LncRNAs were screened. Ultimately, four immune-related LncRNAs were used to construct a formula using LASSO regression. According to the formula, the low-risk group showed a higher survival rate than the high-risk group in the validation cohort and the whole cohort. The receiver operating characteristic curves data demonstrated that the risk score was more specific than other traditional clinical characteristics in predicting the 5-year survival rate for HCC. CONCLUSION: The four-immune-related-LncRNA model can be used for survival prediction in HCC and guide clinical therapy.

Impact of overweightness and critical weight loss on overall survival in patients with hepatocellular carcinoma initially treated with chemoembolization.

BACKGROUND: The effects of overweightness and weight loss on the development and prognosis of hepatocellular carcinoma (HCC) remain unclear. In this study, we aimed to evaluate the impact of overweightness and weight loss on the survival of patients with intermediate/advanced HCC receiving chemoembolization as initial treatment. METHODS: We examined 1,170 patients who underwent chemoembolization as initial treatment for Barcelona-Clínic Liver Cancer stages B and C HCC at Sun Yat-sen University Cancer Center (Guangzhou, China) between December 2009 and May 2015. A baseline body mass index (BMI) of ≥23 kg/m2 was defined as overweight, and body-weight loss of ≥5.0% from baseline was defined as critical weight loss (CWL). Cox regression analysis was used to determine the association between overweightness or CWL and overall survival (OS). RESULTS: The median survival time was 16.8 (95% confidence interval, 13.9-19.7) months and 11.1 (95% confidence interval, 10.0-12.2) months in the overweight and non-overweight groups (log-rank test, P < 0.001), respectively. Cox multivariate analysis identified overweightness as an independent protective prognostic factor for OS (P < 0.001). Subgroup stratification analysis revealed a significant association between overweightness and survival among patients receiving further treatment (P = 0.005), but not in those not receiving further treatment (P = 0.683). Multivariate analysis showed that both overweightness and CWL were independent prognostic factors for OS among patients receiving further treatment. CONCLUSION: Among patients with intermediate- or advanced-stage HCC initially treated with chemoembolization, overweightness was associated with longer OS. Furthermore, CWL was an independent adverse prognostic factor for OS in patients receiving additional treatment.