The causality between systemic inflammatory regulators and chronic respiratory diseases: A bidirectional Mendelian-randomization study.

INTRODUCTION: Accumulative evidence suggests the associations between systemic inflammatory regulators and chronic respiratory diseases (CRDs). However, the intrinsic causation remains implicit. Therefore, this study aimed to examine causative associations by mendelian randomization (MR) and to identify valuable active factors. METHODS: Based on data from the GWAS database, we performed MR analyses of 41 serum cytokines from 8,293 Finnish and European descent cohorts from GBMI and UKBB for five major CRDs. We mainly applied inverse variance weighted regression, supplemented by MR-Egger regression, weighted median, maximum likelihood, weighted mode, and simple mode algorithms. Moreover, sensitivity analyses were conducted using Cochrane's Q test, MR-Egger intercept, MR-PRESSO Global test and MR-Steiger filtering. Eventually, the consistency of MR results was assessed by leave-one-out. RESULTS: Our results suggest that 12 genetically predicted systemic inflammatory regulators probably participate in the progression of CRDs, including four risk factors (IL-1RA, IL-4, MIP-1A, PDGF-BB) and one protective factor (IL-6) in IPF, two protective factors (SCF, SDF-1A) in COPD, and two protective factors (SCF, SDF-1A) in asthma, two protective factors (GROA, IL-2RA) were also included in asthma, whereas only one factor (HGF) was protective against bronchiectasis. Additionally, two protective factors (FGF-BASIC, G-CSF) were identified in sarcoidosis. Sensitivity analyses showed no horizontal pleiotropy and significant heterogeneity. Finally, based on the findings of inverse MR analysis, no inverse causal association was uncovered, confirming the robustness of results. CONCLUSION: Our study unearths potential associations between systemic inflammatory modulators and common CRDs, providing new insights for inflammation-mediated CRD prevention and therapeutic approaches.

METTL14 regulates CD8+T-cell activation and immune responses to anti-PD-1 therapy in lung cancer.

BACKGROUND: N6-methyladenosine (m6A) modification plays an important role in lung cancer. However, methyltransferase-like 14 (METTL14), which serves as the main component of the m6A complex, has been less reported to be involved in the immune microenvironment of lung cancer. This study aimed to analyze the relationship between METTL14 and the immune checkpoint inhibitor programmed death receptor 1 (PD-1) in lung cancer. METHODS: CCK-8, colony formation, transwell, wound healing, and flow cytometry assays were performed to explore the role of METTL14 in lung cancer progression in vitro. Furthermore, syngeneic model mice were treated with sh-METTL14 andan anti-PD-1 antibody to observe the effect of METTL14 on immunotherapy. Flow cytometry and immunohistochemical (IHC) staining were used to detect CD8 expression. RIP and MeRIP were performed to assess the relationship between METTL14 and HSD17B6. LLC cells and activated mouse PBMCs were cocultured in vitro to mimic immune cell infiltration in the tumor microenvironment. ELISA was used to detect IFN-γ and TNF-α levels. RESULTS: The online database GEPIA showed that high METTL14 expression indicated a poor prognosis in patients with lung cancer. In vitro assays suggested that METTL14 knockdown suppressed lung cancer progression. In vivo assays revealed that METTL14 knockdown inhibited tumor growth and enhanced the response to PD-1 immunotherapy. Furthermore, METTL14 knockdown enhanced CD8+T-cell activation and infiltration. More importantly, METTL14 knockdown increased the stability of HSD17B6 mRNA by reducing its m6A methylation. In addition, HSD17B6 overexpression promoted the activation of CD8+ T cells. CONCLUSION: The disruption of METTL14 contributed to CD8+T-cell activation and the immunotherapy response to PD-1 via m6A modification of HSD17B6, thereby suppressing lung cancer progression.

Comparison of Perioperative and Oncological Outcomes of Hybrid and Totally Laparoscopic Pancreatoduodenectomy.

BACKGROUND Laparoscopic pancreatoduodenectomy (LPD) is a complicated procedure accompanied with high morbidity. Hybrid LPD is usually used as an alternative/transitional approach. This study aimed to prove whether the hybrid procedure is a safe procedure during a surgeon's learning curve of LPD. MATERIAL AND METHODS There were 48 hybrid LPD patients and 62 TLPD patients selected from January 2016 to December 2018; their demographics, surgical outcomes, and oncological data were retrospectively collected. Patient follow-up for the study continued until February 2020. RESULTS Patient demographics and baseline parameters were well balanced between the 2 groups. Intraoperative conditions, overall operation time was shorter for TLPD compared to hybrid LPD (407.79 minutes versus 453.29 minutes, respectively; P=0.035) and blood loss was less in TLPD patients compared to hybrid LPD patients (100.00 mL versus 300.00 mL, respectively; P<0.001). There was no difference in transfusion rates between the 2 groups (hybrid LPD 16.7% versus TLPD 4.8%; P=0.084). Postoperative outcomes and intensive care unit (ICU) stay was longer in the hybrid LPD patient group (hybrid LPD 1-day versus TLPD 0-day, P=0.002) and postoperative hospital stay was similar between the 2 groups (P=0.503). Reoperation rates, in-hospital, 30-day mortality, and 90-day mortality rates were comparable between the 2 groups (P=0.276, 1.000, 1.000, 0.884, respectively). Surgical site infection, bile leak, Clavien-Dindo classification (CDC) ≥3, delayed gastric emptying, grade B/C postoperative pancreatic fistulae, and grade B/C post pancreatectomy hemorrhage were not different between the 2 groups (P=0.526, 0.463, 0.220, 0.089, 0.165, 0.757, respectively). The tumor size, margin status, lymph nodes harvested, and metastasis were similar in the 2 groups (P=0.767, 0.438, 0.414, 0.424, respectively). In addition, the median overall survival rates were comparable between the 2 groups (hybrid LPD 29.0 months versus TLPD 30.0 months, P=0.996) as were the progression-free survival rates (hybrid LPD 11.0 months versus TLPD 12.0 months, P=0.373) CONCLUSIONS Hybrid LPD was comparable to TLPD. Hybrid LPD could be performed safely when some surgeons first started LPD (during the operative learning curve), while for skilled surgeons, TLPD could be applied initially.

Effect of laparoscopic splenectomy on portal vein thrombosis and serum YKL-40 in patients with cirrhotic portal hypertension.

INTRODUCTION AND OBJECTIVES: Laparoscopic splenectomy (LS) is a supportive intervention for cirrhotic patients. However, its efficacy for patients with cirrhotic portal hypertension (CPH) still needs clarification. Studies indicated YKL-40 might be effective targets for treatment of splenomegaly, however deeper insights are unclear. The aim of this study was to investigate the effect of LS on the formation of portal vein thrombosis (PVT) and serum levels of a fibrosis marker, YKL-40, in patients with CPH. MATERIALS AND METHODS: A total of 80 patients who underwent LS and 30 healthy controls were investigated in this study. Serum levels of YKL-40 were measured by enzyme-linked immunosorbent assay (ELISA). Demographic characteristics including age and gender were recorded. Clinicopathological and laboratory examinations included the severity of esophageal varices and the presence of viral hepatitis. The liver function was assessed according to the Child-Pugh classification. The incidence of PVT before and after operation was also monitored. RESULTS: Serum YKL-40 was significantly increased in CPH patients, and was associated with Child-Pugh score and HBV infection. Furthermore, elderly patients had an increased risk for postoperative PVT. Higher serum YKL-40 was observed in patients with thrombus at postoperative 7, 14 and 21 days than those without thrombus. CONCLUSIONS: LS could reduce serum YKL-40 levels and PVT progression and was a useful treatment for patients <40 years of age with CPH.

A neural network potential energy surface for the NaH2 system and dynamics studies on the H(2S) + NaH(X1Σ+) → Na(2S) + H2(X1Σg+) reaction.

In order to study the dynamics of the reaction H(2S) + NaH(X1Σ+) → Na(2S) + H2(X1Σg+), a new potential energy surface (PES) for the ground state of the NaH2 system is constructed based on 35 730 ab initio energy points. Using basis sets of quadruple zeta quality, multireference configuration interaction calculations with Davidson correction were carried out to obtain the ab initio energy points. The neural network method is used to fit the PES, and the root mean square error is very small (0.00639 eV). The bond lengths, dissociation energies, zero-point energies and spectroscopic constants of H2(X1Σg+) and NaH(X1Σ+) obtained on the new NaH2 PES are in good agreement with the experiment data. On the new PES, the reactant coordinate-based time-dependent wave packet method is applied to study the reaction dynamics of H(2S) + NaH(X1Σ+) → Na(2S) + H2(X1Σg+), and the reaction probabilities, integral cross-sections (ICSs) and differential cross-sections (DCSs) are obtained. There is no threshold in the reaction due to the absence of an energy barrier on the minimum energy path. When the collision energy increases, the ICSs decrease from a high value at low collision energy. The DCS results show that the angular distribution of the product molecules tends to the forward direction. Compared with the LiH2 system, the NaH2 system has a larger mass and the PES has a larger well at the H-NaH configuration, which leads to a higher ICS value in the H(2S) + NaH(X1Σ+) → Na(2S) + H2(X1Σg+) reaction. Because the H(2S) + NaH(X1Σ+) → Na(2S) + H2(X1Σg+) reaction releases more energy, the product molecules can be excited to a higher vibrational state.

A new potential energy surface of LiHCl system and dynamic studies for the Li(2S) + HCl(X1Σ+) → LiCl(X1Σ+) + H(2S) reaction.

A new global potential energy surface (PES) is constructed for the ground state of LiHCl system based on high-quality ab initio energy points calculated using multi-reference configuration interaction calculations with the Davidson correction. The AVQZ and WCVQZ basis sets are employed for H and Li atoms, respectively. To compensate the relativistic effects of heavy element, the AWCVQZ-DK basis set is employed for Cl atom. The neural network method is used for fitting the PES, and the root mean square error is small (1.36 × 10-2 eV). The spectroscopic constants of the diatoms obtained from the new PES agree well with experimental data. The geometric characteristics of the transition state and the complex are examined and compared with the previous theoretical values. To study the reaction dynamics of the Li(2S) + HCl(X1Σ+) → LiCl(X1Σ+) + H(2S) reaction, quantum reactive scattering dynamics calculations using collection reactant-coordinate-based wave packet method are conducted based on the new PES. The results of the reaction probabilities indicate that a small barrier exists along the reaction path as observed from the PES. The integral cross section curves reveal that the product molecule LiCl is easily excited. In addition, the reaction is dominated by forward scattering, and similar pattern is observed from Becker's experiment.

[Clinical efficacies of different surgical strategies for advanced pancreatic carcinoma].

OBJECTIVE: To explore the clinical efficacies of different surgical strategies for patients with advanced pancreatic carinoma. METHODS: Retrospective analyses were conducted for the clinical data of 223 advanced pancreatic carinoma patients between January 2009 and December 2013 according to the inclusion criteria. And, according to different surgical strategies, they were divided into seed group (n = 49), radio frequency ablation group (n = 51), radiotherapy group (n = 17) and control group (n = 106). The general data, postoperative complications and follow-up profiles between 4 groups were statistically analyzed. RESULTS: The general profiles between four groups were not statistically significant (P > 0.05). There was no mortality. The postoperative complication rate was the highest at 43% (21/49) in seed group. However all complications were of Clavien grade II. The follow-up endpoint was until March 2014. The median follow-up period was 7 (1-52) months. The overall follow-up rate was 88.3% (197/223). And their survival rates of one month, half a year, one year and two years were 95.9%, 53.7%, 19.1% and 7.3% respectively. The average survival time was (9.6 ± 0.3) months. In seed group, the rates were 97.7%, 61.9%, 27.7% and 13.2% respectively. The average survival time was (12.9 ± 1.1) months. In radio frequency ablation group, the rates 88.9%, 54.9%, 22.9% and 7.6% respectively. The average survival time was (9.6 ± 0.9) months. In radiotherapy group, the rates were 93.7%, 56.2%, 18.7% and 6.2% respectively. The average survival time was (8.6 ± 1.4) months. In control group, the rates were 97.8%, 48.9%, 13.8% and 5.4% respectively. The average survival time was (8.5 ± 0.5) months. The survival curves of seed, radio frequency ablation and radiotherapy groups were compared separately with that of control group. The Log-rank test results suggested that the survival rate and mean survival time of seed group were higher than those of control group (P < 0.05). However the radio frequency ablation and radiotherapy groups had no significant difference with control group. CONCLUSIONS: The advanced pancreatic carinoma patients have poor outcomes with a short survival time. The intraoperative implantation of seeds is effective for advanced pancreatic cancer patients, but it also has a high incidence of postoperative complications. Radio frequency ablation and intraoperative radiotherapy fail to effectively prolong the patient survival time.

[Application values of computer-assisted preoperative planning of hilar cholangiocarcinoma].

OBJECTIVE: To explore the application value of computer-assisted preoperative planning of hilar cholangiocarcinoma. METHODS: Retrospective analyses were conducted for the clinical data of 47 patients with hilar cholangiocarcinoma undergoing radical resection plus hemihepatectomy from January to December 2013. According to whether computer-assisted preoperative planning was used, they were divided two groups of computer-assisted surgical planning (CASP) and without computer-assisted surgical planning (WCASP). Then we analyzed the data including preoperative examinations, preoperative planning, intraoperative findings and postoperative complications. RESULTS: There were 31 cases of hilar vascular invasion by tumor. Among 29 cases of CASP, left hepatic artery originated from left gastric artery (n = 6), right posterior bile duct drained into left hepatic bile duct (n = 1) and right posterior bile duct run into common hepatic bile duct (n = 2). The mean operative duration of CASP was (6.5 ± 1.3) h and the mean volume of intraoperative bleeding (672.0 ± 214.3) ml; while the mean operative duration of WCASP was (7.9 ± 2.9) h and the mean volume of intraoperative bleeding (870.0 ± 330.1) ml. By statistical analysis, the inter-group differences of mean operative duration had statistical difference (P = 0.028) and the inter-group differences of mean volume of intraoperative bleeding had statistical difference (P = 0.016). The ratio of first negative test in group CASP was higher than that of group WCASP and the inter-group differences had statistical significance (P = 0.043). But the inter-group rate of postoperative complications had no significant difference (P = 0.419). CONCLUSIONS: The computer-assisted surgical planning system provides accurate information so that an optimal surgical protocol may be designed by surgeons. And it has great application values in preoperative surgical planning for hilar cholangiocarcinoma and enjoys wide prospects in precise liver surgery.

In vivo and in vitro decolorization of synthetic dyes by laccase from solid state fermentation with Trametes sp. SYBC-L4.

Synthetic decolorization of dyes through solid cassava residue substrate fermentation with Trametes sp. SYBC-L4 via in vivo and in vitro processes was investigated in this study. Effects of pH and mediator (1-hydroxybenzotriazole, HBT) concentration on dyes decolorization were evaluated. In vitro, decolorization ratios of dyes differed considerably in pH and increased with the increasing of HBT concentration. Crude laccase (50 U/L) derived from Trametes sp. SYBC-L4 decolorized 67.91 ± 1.25 % Congo red (100 mg/L), 94.58 ± 1.05 % aniline blue (100 mg/L) and 99.02 ± 0.54 % indigo carmine (100 mg/L) with 2.5 mM HBT at pH 4.5 in 36 h of incubation. In vivo, decolorization ratios of dyes were not enhanced by usage of the mediator. After 10 days of fermentation, decolorization ratio of Congo red (1,000 mg/kg), aniline blue (1,000 mg/kg) and indigo carmine (1,000 mg/kg) was 57.82 ± 0.84, 92.53 ± 1.12 and 97.26 ± 1.92 % without the usage of mediator at pH 4.5, respectively. Moreover, there was no obvious difference between the in vivo decolorization of aniline blue and indigo carmine in the pH range of 3.0-9.0. Results showed that Trametes sp. SYBC-L4 had great potential to be used for dyes decolorization via in vivo and in vitro processes. Moreover, in terms of pH range and mediator, in vivo decolorization with Trametes sp. SYBC-L4 was more advantageous since laccase mediator was needless and the applicable range of pH was broader.

Evaluation of Bacillus sp. MZS10 for decolorizing Azure B dye and its decolorization mechanism.

To evaluate decolorization and detoxification of Azure B dye by a newly isolated Bacillus sp. MZS10 strain, the cultivation medium and decolorization mechanism of the isolate were investigated. The decolorization was discovered to be dependent on cell density of the isolate and reached 93.55% (0.04 g/L) after 14 hr of cultivation in a 5 L stirred-tank fermenter at 2.0 g/L yeast extract and 6.0 g/L soluble starch and a small amount of mineral salts. The decolorization metabolites were identified with ultra performance liquid chromatography-tandem mass spectroscopy (UPLC-MS). A mechanism for decolorization of Azure B was proposed as follows: the C=N in Azure B was initially reduced to -NH by nicotinamide adenine dinucleotide phosphate (NADPH)-dependent quinone dehydrogenase, and then the -NH further combined with -OH derived from glucose to form a stable and colorless compound through a dehydration reaction. The phytotoxicity was evaluated for both Azure B and its related derivatives produced by Bacillus sp. MZS10 decolorization, indicating that the decolorization metabolites were less toxic than original dye. The decolorization efficiency and mechanism shown by Bacillus sp. MZS10 provided insight on its potential application for the bioremediation of the dye Azure B.

Oxygen vacancy healing boosts the piezoelectricity of bone scaffolds.

Although barium titanate (BaTiO3) presented tremendous potential in achieving self-powered stimulation to accelerate bone repair, pervasive oxygen vacancies restricted the full play of its piezoelectric performance. Herein, BaTiO3-GO nanoparticles were synthesized by the in situ growth of BaTiO3 on graphene oxide (GO), and subsequently introduced into poly-L-lactic acid (PLLA) powders to prepare PLLA/BaTiO3-GO scaffolds by laser additive manufacturing. During the synthesis process, CO and C-OH in GO would respectively undergo cleavage and dehydrogenation at high temperature to form negatively charged oxygen groups, which were expected to occupy positively charged oxygen vacancies in BaTiO3 and thereby inhibit the formation of oxygen vacancies. Moreover, GO could be partially reduced to reduced graphene oxide, which could act as a conductive phase to facilitate polarization charge transfer, thus further improving the piezoelectric performance. The results showed that the oxygen peak at the specific electron binding energy in O 1s declined from 54.4% to 14.6% and the Ti3+ peak that was positively correlated with oxygen vacancies apparently weakened for BaTiO3-GO, illustrating that the introduced GO significantly decreased the oxygen vacancy. As a consequence, the piezoelectric current of PLLA/BaTiO3-GO increased from 80 to 147.3 nA compared with that of PLLA/BaTiO3. The enhanced piezoelectric current effectively accelerated cell differentiation by upregulating alkaline phosphatase expression, calcium salt deposition and calcium influx. This work provides a novel insight for the design of self-powered stimulation scaffolds for bone regeneration.

The diagnostic potential role of thioredoxin reductase and TXNRD1 in early lung adenocarcinoma: A cohort study.

Background: Lung adenocarcinoma (LUAD) is the primary form of lung cancer, yet the reliable biomarkers for early diagnosis remain insufficient. Thioredoxin reductase (TrxR) is strongly linked to the occurrence, development, and drug resistance of lung cancer, making it a potential biomarker. However, further research is required to assess its diagnostic value in LUAD. Methods: A retrospective analysis was performed on patients who underwent pulmonary nodule resection at our center from 2018 to 2022. Clinical data, including preoperative TrxR levels, imaging, and laboratory characteristics, were identified as study variables. Two prediction models were constructed using multiple logistic regression, and their prediction performance was evaluated comprehensively. Besides, bioinformatics analyses of TrxR coding genes including differential expression, functional enrichment, immune infiltration, drug sensitivity, and single-cell landscape were performed based on TCGA database, which were subsequently validated by Human Protein Atlas. Results: A total of 506 eligible patients (72 benign lesions, 77 AISs, 185 MIAs and 172 IACs) were identified in the clinical cohort. Two TrxR-based models were developed, which were able to distinguish between benign and malignant pulmonary nodules, as well as pathological subtypes of LUAD, respectively. The models exhibited good predictive ability with all AUC values ranging from 0.7 to 0.9. Based on calibration curves and clinical decision analysis, the nomogram models showed high reliability. Functional analysis indicated that TXNRD1 primarily participated in cell cycle and lipid metabolism. Immune infiltration analysis showed that TXNRD1 has a strong association with immune cells and could impact immunotherapy. Then, we identified small molecular compounds that inhibit TXNRD1 and confirmed TXNRD1 expression by single-cell landscape and immunohistochemistry. Conclusion: This study validated the diagnostic value of TrxR and TXNRD1 in clinical cohorts and transcriptional data, respectively. TrxR and TXNRD1 could be used in the risk diagnosis of early LUAD and facilitate personalized treatment strategies.

Exploring prognostic and immunological characteristics of pancreatic ductal adenocarcinoma through comprehensive genomic analysis of tertiary lymphoid structures and CD8 + T-cells.

PURPOSE: Tertiary lymphoid structures (TLSs) and CD8 + T-cells are potential prognostic indicators for pancreatic ductal adenocarcinoma (PDAC). We established a novel scoring system for evaluating the risk for PDAC based on TLS- and CD8 + T-cell-related genes. METHODS: We analyzed single-cell sequence data from PDAC patients in the Genome Sequence Archive. Bioinformatics and machine algorithms established and validated a scoring method (T-C score) based on PDAC survival-related genes highly expressed in TLSs and CD8 + T-cells. Patients were stratified into the low- and high-T-C score groups. Differences in survival, pathway enrichment, mutation status, immune cell infiltration, expression of immune checkpoint-associated genes, tumor stemness, and response to antitumor therapy were compared through computer simulation methods. RESULTS: Overall survival differed significantly between the training and validation cohorts' low- and high-T-C score groups. The low-T-C score group correlated with lower tumor mutation burden and lower levels of tumor stemness compared with the high-T-C score group. Patients with lower T-C scores exhibited advantages in immunotherapeutic responses and might be more sensitive to the chemotherapeutic regimen and multi-kinase inhibitors. CONCLUSION: The T-C score could serve as an effective model for predicting the survival and therapeutic responses of patients with PDAC.

A CuS@g-C3N4 heterojunction endows scaffold with synergetic antibacterial effect.

Graphitic carbon nitride (g-C3N4) had aroused tremendous attention in photodynamic antibacterial therapy due to its excellent energy band structure and appealing optical performance. Nevertheless, the superfast electron-hole recombination and dense biofilm formation abated its photodynamic antibacterial effect. To this end, a nanoheterojunction was synthesized via in-situ growing copper sulfide (CuS) on g-C3N4 (CuS@g-C3N4). On the one hand, CuS could form Fermi level difference with g-C3N4 to accelerate carrier transfer and thus facilitate electron-hole separation. On the other hand, CuS could respond near-infrared light to generate localized thermal to disrupt biofilm. Then the CuS@g-C3N4 nanoparticle was introduced into the poly-l-lactide (PLLA) scaffold. The photoelectrochemistry results demonstrated that the electron-hole separation efficiency was apparently enhanced and thereby brought an approximate sevenfold increase in reactive oxygen species (ROS) production. The thermal imaging indicated that the scaffold possesses a superior photothermal effect, which effectively eradicated the biofilm by disrupting its extracellular DNA and thereby facilitated to the entry of ROS. The entered ROS could effectively kill the bacteria by causing protein, K+, and nucleic acid leakage and glutathione consumption. As a consequence, the scaffold displayed an antibacterial rate of 97.2% and 98.5% against E. coli and S. aureus, respectively.

Interactions between gold nanoparticles with different morphologies and human serum albumin.

Introduction: Three different shapes of gold nanoparticles were synthesized in this experiment. At the same time, studies compared their effects with human serum albumin (HSA). Methods: Gold nanoparticles (AuNPs) with three different morphologies, such as, nanospheres (AuNSs), nanorods (AuNRs), and nanoflowers (AuNFs) were synthesized via a seeding method and their characteristic absorption peaks were detected using ultraviolet-visible (UV-vis) absorption spectroscopy, Telectron microscopy (TEM), Dynamic Light Scattering (DLS) and Zeta potential measurements, circular dichroism (CD), and Fourier transform infrared spectroscopy (FTIR) to study the interactions between them and HSA. By comparing the thermodynamic parameters and quenching mechanism of the three materials, similarities and differences were determined in their interactions with HSA. Results: The results showed that with an increase in the concentration of the AuNPs with the three different morphologies, the UV-vis absorption peak intensity of the mixed solution increased, but its fluorescence intensity was quenched. This indicates that the three types of AuNPs interact with HSA, and that the interactions between them represent a static quenching process, which is consistent with the conclusions derived from three-dimensional fluorescence experiments. Through variable-temperature fluorescence experiments, the binding constants, number of binding sites, and thermodynamic parameters of the interactions between the three types of AuNPs and HSA were determined. The Gibbs free energy changes were <0, indicating that the reactions of the three types of AuNPs with HSA are spontaneous, resulting in associated matter. Binding constant measurements indicated that the strongest binding took place between the AuNFs and HSA. In addition, the results of fluorescence, CD spectroscopy, and FTIR showed that three different shapes of AuNPs can induce conformational changes in HSA and reduce the α-helix content. Among them, AuNFs have the smallest ability to induce conformational changes. Discussion: According to studies, AuNFs interact more favorably with HSA. This can be used as a reference for the administration of drugs containing AuNPs.

The multi-omics analysis identifies a novel cuproptosis-anoikis-related gene signature in prognosis and immune infiltration characterization of lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) has emerged as one of the most aggressive lethal cancers. Anoikis serves as programmed apoptosis initiated by the detachment of cells from the extracel-lular matrix. Cuproptosis is distinct from traditional cell death modalities. The above two modes are both closely related to tumor progression, prognosis, and treatment. However, whether they have synergistic effects in LUAD deserves further investigation. Methods: The anoikis-related prognostic genes (ANRGs) co-expressed with cuproptosis-associated genes (CAGs) were screened using correlation analysis, analysis of variance, least absolute shrinkage, and selection operator (LASSO), and COX regression followed by functional analysis, and then LUAD risk score model was constructed. Using consensus clustering, the relationship between different subtypes and clinicopathological features, immune infiltration characteristics, and somatic mutations was analyzed. A nomogram was developed by incorporating clinical information, which provided a prediction of the survival of patients. Finally, a comprehensive analysis of ANRGs was performed and verified by the HPA database. Results: A total of 27 ANRGs associated with cuproptosis were obtained. On this basis, three distinct ANRGs subtypes were identified, and the differences between clinical prognosis and immune infiltration were observed. A risk score model has been constructed by incorporating seven ANRGs signatures (EIF2AK3, IKZF3, ITGAV, OGT, PLK1, TRAF2, XRCC5). A highly reliable nomogram was developed to help formulate treatment strategies based on risk score and the clinicopathological features of LUAD. The seven-gene signature was turned out to be strongly linked to immune cells and validated in single-cell data. Immunohistochemistry proved that all of them are highly expressed in LUAD tissues. Conclusion: This study reveals the potential relationship between cuproptosis-related ANRGs and clinicopathological features, tumor microenvironment (TME), and mutation characteristics, which can be applied for predicting the prognosis of LUAD and help develop individualized treatment strategies.

Feasibility of laparoscopic enucleation for hemangioma in special hepatic segments.

Background and aim: This study aims to evaluate the safety and efficacy of laparoscopic enucleation for liver hemangioma in special hepatic segments. Methods: We retrospectively reviewed 58 patients who underwent laparoscopic surgery for hepatic hemangioma at a single center from January 2016 to January 2022. Segments I, IVa, VII, and VIII are defined as special hepatic segments, attributing to the bad visualization and adjacent to important vessels such as hepatic veins and inferior vena cava that lead to a high risk in laparoscopic surgery. Patients were categorized into a special location group (SLG) and a normal location group (NLG) according to the location of hemangioma. General data, intraoperative and postoperative outcomes, and postoperative complications of the two groups were compared and analyzed. Results: There were no significant differences in age (p = 0.288), gender (p = 0.331), body mass index (p = 0.168), the maximum diameter of hemangioma (p = 0.330), ASA risk grading (p = 0.615), and comorbidities (p > 0.05) between the two groups. The operation time (p < 0.001), intraoperative blood loss (p < 0.001), and intraoperative blood transfusion rate (p = 0.047) were significantly higher in the SLG. The rate of conversion to laparotomy was higher in the SLG, but there was no significant difference (p = 0.089). In addition, the exhaust time (p = 0.03) and postoperative hospital stay (p < 0.01) were significantly shorter in the NLG. The postoperative complications were comparable between the two groups, and there were no perioperative deaths. Conclusion: Laparoscopic enucleation of hemangioma in special hepatic segments is difficult and has a critical risk of massive bleeding during surgery. Meanwhile, it is also safe, feasible, and effective.

Characterizing PTP4A3/PRL-3 as the Potential Prognostic Marker Gene for Liver Hepatocellular Carcinoma.

Background: A large number of cancer-related deaths in the world can be attributed to liver hepatocellular carcinoma (LIHC). The purpose of this study is to explore protein tyrosine phosphatase type IV A member 3 (PTP4A3/PRL-3) as a new and reliable biomarker to predict the prognosis of LIHC and determine the potential therapeutic targets or drugs that can be used for treating LIHC. Methods: We included three LIHC datasets with clinical information and expression profiles from public databases. The expression level of PTP4A3 was analyzed, and based on the results, the samples were divided into high- and low-expression groups. The Kaplan-Meier survival analysis method was used to determine the relationship between PTP4A3 and prognosis. The enrichment differences among the functional pathways associated with the high- and low-expression groups were determined using the gene set enrichment analysis (GSEA) method. Five methods were used to determine the differences among the tumor microenvironment in the low- and high-expression groups. The sensitivity of the low- and high-expression groups toward different drug treatment methods was predicted by analyzing the Tumor Immune Dysfunction and Exclusion (TIDE) scores and determining the biochemical half-maximal inhibitory concentration (IC50). Results: The expression levels of the LIHC and adjacent samples were analyzed, and it was observed that the expression level of PTP4A3 in tumor tissue was significantly higher than the expression level of the same gene in the adjacent samples. It was also inferred that it might be a cancer-promoting gene. It was concluded that high-expression results in a significantly poor prognosis. The high-expression group was significantly enriched in the tumor-related pathways, such as the PI3K-AKT signaling pathway. In addition, the results obtained by conducting immune infiltration analysis revealed a significant positive correlation between some immune scores and the gene PTP4A3. The drug KIN001-135 and gene PTP4A3 were also found to correlate positively with each other. CP466722, Pyrimethamine, AKT inhibitor VIII, Embelin, Cisplatin, QS11, Bexarotene, and Midostaurin negatively correlated with PTP4A3 associated with the three datasets. Moreover, the drugs Cisplatin, QS11, Midostaurin, and CP466722 were more sensitive toward the high-expression group than the low PTP4A3 expression group. Significant differences were observed in these cases. Conclusion: PTP4A3/PRL-3 is potentially associated with the progression, metastasis, and invasion of LIHC. The prognosis of LIHC patients is negatively impacted by the high-expression levels of the gene. The results indicate that PTP4A3/PRL-3 is an important prognostic factor for LIHC and is a new potential prognostic detection target. The discovery of the 8 drugs that were negatively associated with PTP4A3 provided a new direction that can be developed in the future for the treatment of LIHC.

Lung transplantation for bronchiolitis obliterans after hematopoietic stem cell transplantation: a retrospective single-center study.

Background: Bronchiolitis obliterans (BO) is one of the most common late non-infectious pulmonary complications after hematopoietic stem cell transplantation (HSCT). Lung transplantation (LT) is the only cure for patients with end-stage BO, but the overall efficacy is rarely reported. Our study aims to conclude and elucidate the clinical experience of our single center and provide a reference for the current selection of treatment. Methods: We retrospectively analyzed the medical records of six patients with post-HSCT BO who received LT in our center from 2015 to 2019. The collected information included demographic data, surgery-related conditions, and postoperative follow-up data, which covered blood tests, infection status assessment, lung function assessment, anesthesia assessment, function assessment of other organs and so on. All patients were regularly followed up after discharge, which in the first year, was performed every 3 months. Over the next 2 years, patients were assessed every 6 months, and after 3 years, the frequency was once annually. Results: The mean age of patients at LT time was 28±13 years, with an interval of 72±48 months from HSCT. All patients developed hypercapnia with an average carbon dioxide partial pressure (pCO2) of 71.1±20.8 mmHg. Preoperative pulmonary function tests showed the mean actual forced expiratory volume in 1 second (FEV1) was 16.7%±5.9% of the predicted value in four patients. After assessment, four patients adopted sequential bilateral LT and two adopted right-sided LT. Due to hemodynamic instability, five patients adopted intraoperative assistance of extracorporeal membrane oxygenation (ECMO). One patient died of septic shock 9 days after surgery, and the other five survived healthy for 53±23 months. The actual value of FEV1 at 3 months postoperatively accounted for 57.9%±15.3% of the predicted value. No patients had recurrence of BO. Conclusions: LT may be a treatment worthy of consideration in patients with post-HSCT end-stage BO because it can improve lung function, quality of life and prolong survival of these selected patients.

Four circadian rhythm-related genes predict incidence and prognosis in hepatocellular carcinoma.

Circadian dysregulation can be involved in the development of malignant tumors, though its relationship with the progression of hepatocellular carcinoma is not yet fully understood. We identified genes related to circadian rhythms from the Cancer Genome Atlas (TCGA), measured gene expression, and conducted genomic difference analysis to construct a circadian rhythm-related signature. The resulting prognosis model proved to be an effective biomarker, as demonstrated by Kaplan-Meier survival analysis for both the training (n = 370, P = 2.687e-10) and external validation cohorts (n = 230, P = 1.45e-02). Further, we found that patients considered 'high risk', with an associated poor prognosis, displayed elevated levels of immune checkpoint genes and immune filtration. We also conducted functional enrichment, which indicated that the risk model showed a significant positive correlation with certain malignant phenotypes, including G2M checkpoint, MYC targets, and the MTORC1 signaling pathway. In summary, we identified a novel circadian rhythm-related signature allowing assessment of prognosis for hepatocellular carcinoma patients, and further can be used to predict immune infiltration sensitivity.