Delta magnetic resonance imaging radiomics features­based nomogram predicts long­term efficacy after induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: To establish and validate a delta-radiomics-based model for predicting progression-free survival (PFS) in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) following induction chemotherapy (IC). METHODS AND MATERIALS: A total of 250 LA-NPC patients (training cohort: n = 145; validation cohort: n = 105) were enrolled. Radiomic features were extracted from MRI scans taken before and after IC, and changes in these features were calculated. Following feature selection, a delta-radiomics signature was constructed using LASSO-Cox regression analysis. A prognostic nomogram incorporating independent clinical indicators and the delta-radiomics signature was developed and assessed for calibration and discrimination. Risk stratification by the nomogram was evaluated using Kaplan-Meier methods. RESULTS: The delta-radiomics signature, consisting of 12 features, was independently associated with prognosis. The nomogram, integrating the delta-radiomics signature and clinical factors demonstrated excellent calibration and discrimination. The model achieved a Harrell's concordance index (C-index) of 0.848 in the training cohort and 0.820 in the validation cohort. Risk stratification identified two groups with significantly different PFS rates. The three-year PFS for high-risk patients who received concurrent chemoradiotherapy (CCRT) or radiotherapy plus adjuvant chemotherapy (RT+AC) after IC was significantly higher than for those who received RT alone, reaching statistical significance. In contrast, for low-risk patients, the three-year PFS after IC was slightly higher for those who received CCRT or RT+AC compared to those who received RT alone; however, this difference did not reach statistical significance. CONCLUSIONS: Our delta MRI-based radiomics model could be useful for predicting PFS and may guide subsequent treatment decisions after IC in LA-NPC.

Anti-PD-L1 checkpoint inhibitor combined with nanocarrier-mediated cisplatin codelivery system for effective treatment of pancreatic cancer.

Immune checkpoint inhibitor-based cancer immunotherapy has shown promise as a potential treatment in the clinic. It has been reported that anti-PD-L1 combined with cisplatin treatment can improve the antitumor effect. However, the therapeutic outcome is limited due to the abundance of tumor stroma in pancreatic cancer (PC), which prevented the penetration of cisplatin and anti-PD-L1 into tumor regions, thus impeding the effectiveness in the treatment of PC. In this study, a nanocarrier-mediated codelivery system of hyaluronidase and cisplatin was constructed, which can degrade the stroma and promote cisplatin and anti-PD-L1 to penetrate the tumor stroma into the deep tumor, so as to suppress PC effectively. When combined the cisplatin nanocarrier system BPEI-SS-Pt/HAase@CaP (BSP/H@CaP) with an immune checkpoint inhibitor to overcome the poor therapeutic outcome of PC, the results indicated that the therapeutic effect of BSP/H@CaP combined with anti-PD-L1 was better than that of BSP/H@CaP and single anti-PD-L1 group. Because the stroma is degrading, a higher amount of BPEI-SS-Pt and anti-PD-L1 can enter the tumor stroma and reach the inner depths of the tumor for immune stimulation, leading to a synergistically augmented chemotherapy and immunotherapy for PC. The above combination therapy is useful for clinical translation to overcome the treatment resistance of matrix-rich PC.

Inhibiting the activation of enteric glial cells alleviates intestinal inflammation and comorbid anxiety- and depressive-like behaviors in the ulcerative colitis mice.

Ulcerative colitis (UC) is a common inflammatory bowel disease with a complex origin in clinical settings. It is frequently accompanied by negative emotional responses, including anxiety and depression. Enteric glial cells (EGCs) are important components of the gut-brain axis and are involved in the development of the enteric nervous system (ENS), intestinal neuroimmune, and regulation of intestinal motor functions. Since there is limited research encompassing the regulatory function of EGCs in anxiety- and depression-like behaviors induced by UC, this study aims to reveal their regulatory role in such behaviors and associated intestinal inflammation. This study applied morphological, molecular biological, and behavioral methods to observe the morphological and functional changes of EGCs in UC mice. The results indicated a significant activation of EGCs in the ENS of dextran sodium sulfate -induced UC mice. This activation was evidenced by morphological alterations, such as elongation or terminal swelling of processes. Besides EGCs activation, UC mice exhibited significantly elevated expression levels of pro-inflammatory cytokines in the peripheral blood, accompanied by anxiety- and depression-like behaviors. The inhibition of EGCs activity within the ENS can ameliorate the anxiety- and depression-like behaviors caused by UC. Our data suggest that UC and its resulting behaviors may be related to the activation of EGCs within the ENS. Moreover, the modulation of intestinal inflammation through inhibition of EGCs activation emerges as a promising clinical approach for alleviating UC-induced anxiety- and depression-like behaviors.

Integrative Analysis of the Microbiome and Metabolome of Broiler Intestine: Insights into the Mechanisms of Probiotic Action as an Antibiotic Substitute.

Antibiotic substitutes have become a research focus due to restrictions on antibiotic usage. Among the antibiotic substitutes on the market, probiotics have been extensively researched and used. However, the mechanism by which probiotics replace antibiotics remains unclear. In this study, we aimed to investigate this mechanism by comparing the effects of probiotics and antibiotics on broiler growth performance and intestinal microbiota composition. Results shown that both probiotics and antibiotics increased daily weight gain and reduced feed conversion rate in broilers. Analysis of ileum and cecum microorganisms via 16S rRNA gene sequencing revealed that both interventions decreased intestinal microbial diversity. Moreover, the abundance of Bacteroides increased in the mature ileum, while that of Erysipelatoclostridium decreased in the cecum in response to both probiotics and antibiotics. The main metabolites of probiotics and antibiotics in the intestine were found to be organic acids, amino acids, and sugars, which might play comparable roles in growth performance. Furthermore, disaccharides and trisaccharides may be essential components in the ileum that enable probiotics to replace antibiotics. These findings provide important insights into the mechanisms underlying the use of probiotics as antibiotic substitutes in broiler breeding.

A novel surgical scheme for hepatectomy in hepatocellular carcinoma patients with clinically significant portal hypertension.

OBJECTIVE: Clinically significant portal hypertension (CSPH) seriously affects the feasibility and safety of surgical treatment for hepatocellular carcinoma (HCC) patients. The aim of this study was to establish a new surgical scheme defining risk classification of post-hepatectomy liver failure (PHLF) to facilitate the surgical decision-making and identify suitable candidates for individual hepatectomy among HCC patients with CSPH. BACKGROUNDS: Hepatectomy is the preferred treatment for HCC. Surgeons must maintain a balance between the expected oncological outcomes of HCC removal and short-term risks of severe PHLF and morbidity. CSPH aggravates liver decompensation and increases the risk of severe PHLF thus complicating hepatectomy for HCC. METHODS: Multivariate logistic regression and stochastic forest algorithm were performed, then the independent risk factors of severe PHLF were included in a nomogram to determine the risk of severe PHLF. Further, a conditional inference tree (CTREE) through recursive partitioning analysis validated supplement the misdiagnostic threshold of the nomogram. RESULTS: This study included 924 patients, of whom 137 patients (14.8%) suffered from mild-CSPH and 66 patients suffered from (7.1%) with severe-CSPH confirmed preoperatively. Our data showed that preoperative prolonged prothrombin time, total bilirubin, indocyanine green retention rate at 15 min, CSPH grade, and standard future liver remnant volume were independent predictors of severe PHLF. By incorporating these factors, the nomogram achieved good prediction performance in assessing severe PHLF risk, and its concordance statistic was 0.891, 0.850 and 0.872 in the training cohort, internal validation cohort and external validation cohort, respectively, and good calibration curves were obtained. Moreover, the calculations of total points of diagnostic errors with 95% CI were concentrated in 110.5 (range 76.9-178.5). It showed a low risk of severe PHLF (2.3%), indicating hepatectomy is feasible when the points fall below 76.9, while the risk of severe PHLF is extremely high (93.8%) and hepatectomy should be rigorously restricted at scores over 178.5. Patients with points within the misdiagnosis threshold were further examined using CTREE according to a hierarchic order of factors represented by the presence of CSPH grade, ICG-R15, and sFLR. CONCLUSION: This new surgical scheme established in our study is practical to stratify risk classification in assessing severe PHLF, thereby facilitating surgical decision-making and identifying suitable candidates for individual hepatectomy.

Injectable hybrid hydrogels enable enhanced combination chemotherapy and roused anti-tumor immunity in the synergistic treatment of pancreatic ductal adenocarcinoma.

Chemotherapy and immunotherapy have shown no significant outcome for unresectable pancreatic ductal adenocarcinoma (PDAC). Multi-drug combination therapy has become a consensus in clinical trials to explore how to arouse anti-tumor immunity and meanwhile overcome the poorly tumoricidal effect and the stroma barrier that greatly hinders drug penetration. To address this challenge, a comprehensive strategy is proposed to fully utilize both the ferroptotic vulnerability of PDAC to potently irritate anti-tumor immunity and the desmoplasia-associated focal adhesion kinase (FAK) to wholly improve the immunosuppressive microenvironment via sustained release of drugs in an injectable hydrogel for increasing drug penetration in tumor location and averting systematic toxicity. The injectable hydrogel ED-M@CS/MC is hybridized with micelles loaded with erastin that exclusively induces ferroptosis and a FAK inhibitor defactinib for inhibiting stroma formation, and achieves sustained release of the drugs for up to 12 days. With only a single intratumoral injection, the combination treatment with erastin and defactinib produces further anti-tumor performance both in xenograft and KrasG12D-engineered primary PDAC mice and synergistically promotes the infiltration of CD8+ cytotoxic T cells and the reduction of type II macrophages. The findings may provide a novel promising strategy for the clinical treatment of PDAC.

Elevated aerosol enhances plant water-use efficiency by increasing carbon uptake while reducing water loss.

Aerosols could significantly influence ecosystem carbon and water fluxes, potentially altering their interconnected dynamics, typically characterized by water-use efficiency (WUE). However, our understanding of the underlying ecophysiological mechanisms remains limited due to insufficient field observations. We conducted 4-yr measurements of leaf photosynthesis and transpiration, as well as 3-yr measurements of stem growth (SG) and sap flow of poplar trees exposed to natural aerosol fluctuation, to elucidate aerosol's impact on plant WUE. We found that aerosol improved sun leaf WUE mainly because a sharp decline in photosynthetically active radiation (PAR) inhibited its transpiration, while photosynthesis was less affected, as the negative effect induced by declined PAR was offset by the positive effect induced by low leaf vapor pressure deficit (VPDleaf). Conversely, diffuse radiation fertilization (DRF) effect stimulated shade leaf photosynthesis with minimal impact on transpiration, leading to an improved WUE. The responses were further verified by a strong DRF on SG and a decrease in sap flow due to the suppresses in total radiation and VPD. Our field observations indicate that, contrary to the commonly assumed coupling response, carbon uptake and water use exhibited dissimilar reactions to aerosol pollution, ultimately enhancing WUE at the leaf and canopy level.

Dissolution of mixed oxide(MOX) fuel in nitric acid:A review.

The fast neutron reactor is an internationally promising fourth-generation reactor. The main fuel for this reactor is a mixed oxide fuel, and its reprocessing is currently one of the technical challenges being tackled by various countries. One of the difficulties in the reprocessing of mixed oxide (MOX) fuel lies in the nitric acid dissolution process. The high Pu content in MOX fuel can lead to issues such as solvent radiolysis, nuclear criticality, increased insoluble residues, and slow dissolution rates during the nitric acid dissolution process. These challenges have yet to be effectively addressed. This article discusses the chemical aspects of nitric acid dissolution of MOX fuel and investigates the impact of fuel manufacturing processes, the addition of metal catalyst ions, hydrofluoric acid addition, fuel plutonium content, dissolution temperature, and ultrasonic assistance on the nitric acid dissolution of MOX fuel. A review of various countries' engineering practices related to MOX fuel dissolution is presented. Based on the research findings and experiences, a potentially feasible future industrial processing route for MOX fuel is proposed, and future research priorities are outlined.

Radiotherapy is superior to transarterial chemoembolization as adjuvant therapy after narrow-margin hepatectomy in patients with hepatocellular carcinoma: A single-center prospective randomized study.

BACKGROUND: This study was recruited to compare the efficacy and safety of radiotherapy (RT) and transarterial chemoembolization (TACE) as postoperative adjuvant therapy after narrow-margin hepatectomy in hepatocellular carcinoma (HCC) patients. METHODS: This single-center prospective randomized study was conducted in the Cancer Hospital, Guang Xi Medical University, Nanning. A total of 72 patients who received treatment in this hospital between August 2017 and July 2019 were included and randomly allocated to TACE group (n = 48) and RT group (n = 24). Next, overall survival (OS) and progression-free survival (PFS) rates, recurrence patterns, financial burden, and safety were evaluated. RESULTS: The difference between the RT and TACE groups was not significant in one-, three-, and five-year OS (87.5%, 79.0%, and 62.5% vs. 93.8%, 75.9%, and 63.4%, respectively, P = 0.071) and PFS rates (79.0%, 54.2%, and 22.6% vs. 75.0%, 47.9%, and 32.6%, respectively, P = 0.071). Compared to the TACE group, the RT group had significantly lower intrahepatic recurrence rate (20.8% vs. 52.1%, P = 0.011), higher extrahepatic recurrence rate (37.5% vs. 14.6%, P = 0.034), and no marginal and diffuse recurrences (0% vs. 16.7%, P < 0.05). The mean overall treatment cost was higher (¥62,550.59 ± 4397.27 vs. ¥40,732.56 ± 9210.54, P < 0.01), the hospital stay (15.1 ± 3.7 vs. 11.8 ± 4.1 days, P < 0.01) was longer, and the overall treatment stay (13.3 ± 5.3 vs. 41.29 ± 12.4 days, P < 0.01) was shorter in the TACE group than in the RT group. Besides, both groups did not exhibit significant differences in the frequency and severity of adverse events. CONCLUSION: Both adjuvant TACE and RT can better the OS and PFS of patients with HCC. However, RT has a significantly better performance than TACE in terms of improving intrahepatic recurrence rate, treatment cost and hospital stay.

C-Reactive Protein-Albumin Ratio (CAR): A More Promising Inflammation-Based Prognostic Marker for Patients Undergoing Curative Hepatectomy for Hepatocellular Carcinoma.

Background: Systemic inflammatory response is a hallmark of cancer and plays a significant role in the development and progression of various malignant tumors. This research aimed to estimate the prognostic function of the C-reactive protein-albumin ratio (CAR) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC) and compare it with other inflammation-based prognostic scores, including the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, monocyte-lymphocyte ratio, systemic immune inflammation index, prognostic index, Glasgow prognostic score, and modified Glasgow prognostic score. Methods: Retrospective analysis was conducted on data from 1039 HCC cases who underwent curative liver resection. The prognostic performance of CAR was compared with other scores using the area under the time-dependent receiver operating characteristic (t-ROC) curve. Multivariable Cox regression analyses were performed to confirm independent predictors for disease-free survival (DFS) and overall survival (OS). Results: The area under the t-ROC curve for CAR in the evaluation of DFS and OS was significantly greater than that of other scores and alpha-fetoprotein (AFP). Patients were stratified based on the optimal cut-off value of CAR, and the data revealed that both DFS and OS were remarkably worse in the high-CAR set compared to the low-CAR set. Multivariable Cox analysis demonstrated that CAR was an independent prognostic parameters for assessing DFS and OS. Regardless of AFP levels, all patients were subsequently divided into significantly different subgroups of DFS and OS based on CAR risk stratification. Similar results were observed when applying CAR risk stratification to other scoring systems. CAR also showed good clinical applicability in patients with different clinical features. Conclusion: CAR is a more effective inflammation-based prognostic marker than other scores and AFP in predicting DFS as well as OS among patients with HCC after curative hepatectomy.

Establishment of Comprehensive Protection System for Intellectual Property of Single Herbs by Taking Callicarpa nudiflora of Jiuzhitang as An Example / 中国实验方剂学杂志

The development of single Chinese materia medica is an important direction of technological innovation in the field of Chinese materia medica at present， and the study of its comprehensive intellectual property protection system is of great significance to the intellectual property protection of the whole chain of innovative enterprises of single Chinese materia medica. Based on this， this paper takes the comprehensive protection system of intellectual property of Callicarpa nudiflora constructed by Jiuzhitang Pharmaceutical as a model to conduct empirical research， analyzes the protection forms applicable to intellectual property of Chinese materia medica， such as patents， administrative protection， trademarks， designs and intangible cultural heritages， and discusses the valuable and insufficient aspects of the protection system currently constructed by Jiuzhitang Pharmaceutical and puts forward the following suggestions：①paying attention to patent applications for planting/processing methods of raw medicinal materials， ②emphasizing the protection of geographical indications， authentic medicinal herbs， and new plant varieties， ③actively promoting product and technology upgrades， ④applying for data protection during product iteration， ⑤emphasizing the layout timing of patent and administrative protection， ⑥focusing on improving goodwill， ⑦enhancing awareness of intellectual property protection and promoting deep integration of industry， academia， and research. We hope that innovative enterprises engaged in the development of single Chinese materia medica can learn from the experience of the case， and optimize the strategy to better protect related products.

Pharmaceutical care for a patient with paroxysmal spasms of extremities caused by ceftazidime-avibactam / 中国药房

OBJECTIVE To explore the role of clinical pharmacists in identifying paroxysmal spasms caused by drugs， and provide reference for rational drug use. METHODS Retrospective analysis was conducted on pharmaceutical care provided by clinical pharmacists for a patient with ceftazidime-avibactam （CZA-AVI） induced paroxysmal spasms. The clinical pharmacists identified， analyzed and summarized the clinical manifestations， risk factors and treatment methods of the nervous system toxicity caused by antibacterial drugs. According to the patient’s clinical symptoms and test results， the clinical pharmacists recommended temporarily discontinuing the use of polymyxin B and montelukast sodium， and halving the dose of CZA-AVI. The physicians did not adopt the recommendation to halve the dose of CZA-AVI， and when the patient’s neurologic toxicity did not improve， the clinical pharmacists again recommended discontinuing CZA-AVI， which was accepted by the physicians. RESULTS Clinical pharmacists analyzed the condition and checked related drugs that caused paroxysmal spasms of extremities one by one， and finally determined that CZA-AVI might be the drug that caused paroxysmal spasms of extremities in the patient. After stopping the drug， the patient’s symptoms improved and was transferred to a community hospital for rehabilitation treatment. CONCLUSIONS The dose of CZA-AVI should be adjusted according to the renal function and the neurotoxicity should be guarded against， especially for patients with advanced age， renal insufficiency， and the combined use of multiple drugs related to nephrotoxicity and neurotoxicity.

Effect of chelerythrine on migration,invasion,and epithelial-mesenchymal transition of human ovarian cancer SKOV3 cells / 吉林大学学报(医学版)

Objective:To discuss the inhibitory effect of chelerythrine(CHE)on the migration,invasion,and epithelial-mesenchymal transition(EMT)of the human ovarian cancer SKOV3 cells,and to clarify the associated mechanism.Methods:The SKOV3 cells were cultured in vitro and divided into control group and 2.5,5.0,10.0,20.0,and 40.0 μmol·L-1 CHE groups.Methylthiazolydiphenyl-tetrazolium(MTT)assay was used to detect the inhibitory rates of proliferation of the cells in various groups.The SKOV3 cells were cultured in vitro and divided into control group,transforming growth factor-β1(TGF-β1)group,TGF-β1+5 μmol·L-1 CHE group,and TGF-β1+10 μmol·L-1 CHE group.Cell scratch assay was used to detect the migration rates of the cells in various groups;Transwell chamber assay was used to detect the numbers of migration and invasion cells in various groups;Western blotting method was used to detect the expression levels of E-cadherin,N-cadherin,and Vimentin proteins in the cells in various groups;immunofluorescence staining method was used to detect the fluorescence intensities of E-cadherin and N-cadherin in the cells in various groups.Results:The MTT assay results showed that compared with control group,the inhibitory rates of proliferation of the cells in 5.0,10.0,20.0,and 40.0 μmol·L-1 CHE groups were significantly increased(P<0.05 or P<0.01).The cell scratch assay results showed that compared with control group,the migration rate of the cells in TGF-β1 group was increased(P<0.01);compared with TGF-β1 group,the migration rates of the cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly decreased(P<0.01).The Transwell chamber assay results showed that compared with control group,the numbers of migration and invasion cells in TGF-β1 group were significantly increased(P<0.05);compared with TGF-β1 group,the numbers of migration and invasion cells in TGF-β1+5 μmo·l L-1 CHE group and TGF-β1+10 μmo·l L-1 CHE group were significantly decreased(P<0.01).The Western blotting results showed that compared with control group,the expression level of E-cadherin protein in the cells in TGF-β1 group was significantly decreased(P<0.01),while the expression levels of N-cadherin and Vimentin proteins were increased(P<0.05 or P<0.01);compared with TGF-β1 group,the expression levels of E-cadherin protein in the cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly increased(P<0.01),and the expression levels of N-cadherin and Vimentin proteins were significantly decreased(P<0.01).The immunofluorescence staining results showed that compared with control group,the fluorescence intensity of E-cadherin in the cells in TGF-β1 group was decreased,and the fluorescence intensity of N-cadherin was increased;compared with TGF-β1 group,the fluorescence intensities of E-cadherin in the cells in TGF-β 1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly increased,and the fluorescence intensities of N-cadherin were decreased.Conclusion:CHE can inhibit the proliferation,migration,invasion,and EMT of the human ovarian cancer SKOV3 cells.

'Sandwich treatment' for posterior fossa brain metastases with volume larger than 4cm3: a multicentric retrospective study.

Single stereotactic radiosurgery (SRS) for posterior fossa brain metastases (BM) larger than 4cm3 is dangerous. 'Sandwich treatment' strategy was developed for these BMs. The strategy was one week treatment course which includes 2-stage SRS and using Bevacizumab once during SRS gap. Patients from four gamma knife center were retrospectively analyzed. The changes of tumor and peri-tumor edema volume were studied. The Dizziness Handicap Inventory (DHI) Vomiting Score (VS) and Glasgow Coma Scale (GCS) were used to evaluate patients' clinical symptom changes. Karnofsky performance scale (KPS) and Barthel Index (BI) were used to evaluate patients' overall fitness status and physical activity rehabilitation. Tumor local control (TLC) and patients' overall survival (OS) rate were also calculated. Forty patients with 45 LBMs received 'Sandwich treatment'. The mean edema volume reduced remarkably at the course of therapy and 3 months later (P < 0.01). The mean tumor volume greatly decreased 3 months later (P < 0.01). Patients' clinical symptoms that reflected by median score of DHI, VS, GCS were improved dramatically at the course of therapy and 3 months later (P < 0.01). Similar changes happened in median score of KPS and BI that reflected patients' overall fitness status and physical activity rehabilitation (P < 0.01). Patients' median OS was 14.3 months, with 95.4%, 76.2%, and 26.3% survival rate at 6, 12, 24 months. The TLC rate at 6, 12, 24 months was 97.5%, 86.0% and 62.2%.The 'Sandwich treatment' is safe and effective for patients with LBM over 4cm3 in the posterior fossa. The strategy could quickly improve patients' symptoms, well control tumor growth, prolong patient's OS, and has controllable side effects.

Degradation of indole via a two-component indole oxygenase system from Enterococcus hirae GDIAS-5.

Animal farming copiously generates indoles, which contribute to odor and pose a challenge for deodorization. While biodegradation is widely accepted, there is a lack of suitable indole-degrading bacteria for animal husbandry. In this study, we aimed to construct genetically engineered strains with indole-degrading abilities. Enterococcus hirae GDIAS-5 is a highly efficient indole-degrading bacterium, which functions via a monooxygenase YcnE presumably contributes to indole oxidation. However, the efficiency of engineered Escherichia coli expressing YcnE for indole degradation is lower than that of GDIAS-5. To improve its efficacy, the underlying indole-degradation mechanisms in GDIAS-5 were analyzed. An ido operon that responds to a two-component indole oxygenase system was identified. In vitro experiments showed that the reductase component of YcnE, YdgI, can improve the catalytic efficiency. The reconstruction of the two-component system in E. coli exhibited higher indole removal efficiency than GDIAS-5. Furthermore, isatin, the key intermediate metabolite in indole degradation, might be degraded via a novel isatin-acetaminophen-aminophenol pathway involving an amidase whose coding gene is located near the ido operon. The two-component anaerobic oxidation system, upstream degradation pathway, and engineering strains investigated in this study provide important insights into indole degradation metabolism and offer efficient resources for achieving bacterial odor elimination.

Laparoscopic and open liver resection for hepatocellular carcinoma with type 2 diabetes mellitus: multicenter propensity score-matched study.

PURPOSE: This study aimed at analyzing and comparing the perioperative results and long-term oncological outcomes of hepatocellular carcinoma (HCC) patients with type 2 diabetes mellitus (T2DM) treated with laparoscopic (LLR) versus open liver resection (OLR). METHODS: Clinicopathological data of HCC patients with T2DM who underwent LLR or OLR as initial treatment from four medical centers were retrospectively reviewed. The survival outcomes of patients who underwent laparoscopic liver resection (LLR) were compared with those of patients who underwent open liver resection (OLR). Using the Kaplan-Meier method, survival curves for the two groups of patients were generated, and the log-rank test was used to compare survival differences. Propensity score matching (PSM) analysis was used to match patients of the LLR and OLR groups in a 1:1 ratio. RESULTS: 230 HCC patients with T2DM were enrolled, including 101 patients in the LLR group and 129 patients in the OLR group. After PSM, 90 patients were matched in each of the study group. Compared with the OLR group, the LLR group had less blood loss, a shorter hospitalization and fewer postoperative complications. The LLR group had a significantly better overall survival (OS) and recurrence-free survival (RFS) than the OLR group before and after PSM. Subgroup analysis demonstrated that HCC patients with T2DM had survival benefits from LLR regardless of the course of T2DM. CONCLUSIONS: Laparoscopic liver resection for HCC patients with T2DM can be safely performed with favorable perioperative and long-term oncological outcomes at high-volume liver cancer centers, regardless of the course of T2DM.

PD-1 inhibitor plus anlotinib for metastatic castration-resistant prostate cancer: a real-world study.

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.

PD-1 inhibitor plus anlotinib for metastatic castration-resistant prostate cancer: a real-world study / 亚洲男科学杂志(英文版)

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.

A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.

Meta-analysis of the efficacy of small incision lenticule extraction for astigmatism correction after cyclotorsion compensation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the efficacy of and without small incision lenticule extraction(SMILE)with cyclotorsion compensation for astigmatism correction.METHODS: PubMed, Web of Science, EMBASE, Cochrane and CNKI, VIP, CBM, and Wan Fang Data were searched for clinically controlled studies from January 2010 to August 2022, including an experimental group with cyclotorsion compensation during SMILE and a control group without cyclotorsion compensation during SMILE. After literature screening, quality evaluation, and data extraction by two researchers independently, the Meta-analysis of uncorrected distance visual acuity(UDVA), residual astigmatism, vector analysis indicators for measuring the astigmatism correction including absolute value of angle of error(|AE|)and magnitude error(ME), and post-operative total higher order aberrations, spherical aberration and coma was carried out with Stata 16.0 software.RESULTS: Seven studies with a total of 846 eyes(442 in the experimental group, 404 in the control group)were finally included. The Meta-analysis showed that there were significant differences in the percentage of eyes with residual astigmatism ≥1.00D(OR=0.17, 95%CI: 0.06～0.49, P&#x003C;0.01), |AE|(WMD=-1.56, 95%CI: -2.68～-0.45, P&#x003C;0.01), the coma(WMD=0.06, 95%CI: -0.08～-0.04, P&#x003C;0.01), and the total higher order aberrations(WMD=-0.04, 95%CI: -0.06～-0.02, P&#x003C;0.01). However, there were no differences in the postoperative UDVA(WMD=0.00, 95%CI: -0.02～0.01, P=0.54), residual astigmatism(WMD=0.08, 95%CI: -0.02～0.18, P=0.10), ME(WMD=-0.01, 95%CI: -0.14～0.12, P=0.85), and the spherical aberration(WMD=0.03, 95%CI: -0.07～0.13, P=0.52).CONCLUSION: Cyclotorsion compensation in SMILE can reduce the angular error caused by eye rotation during astigmatism correction. It also decreases postoperative residual astigmatism. Overall, the SMILE with cyclotorsion compensation is superior in clinical efficacy of the precise correction of astigmatism.