Pentacyclic triterpenoids as potential ACL inhibitors from the rare medicinal plant Semiliquidambar cathayensis.

An extensive phytochemical investigation on the rare medicinal plant Semiliquidambar cathayensis (family: Hamamelidaceae) led to the isolation of four new (1-4, named semiliquidacids A-D, respectively) and 25 related known pentacyclic triterpenoids. The new structures with absolute configurations were elucidated by spectroscopic methods, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Compound 1 represents the first naturally occurring ursane-type triterpenoid featuring an uncommon C-25 formyl group. Compound 4 and oleanolic acid (13) exhibited remarkable inhibitory effects against the ATP-citrate lyase (ACL, an emerging drug target for hyperlipidemia and related metabolic disorders) with IC50 values of 6.5 and 11.9 µM, respectively. The molecular interaction and binding mode between the bioactive triterpenoids and ACL were elaborated by conducting a molecular docking study. Meanwhile, the chemotaxonomic significance of the isolated triterpenoids has been briefly discussed.

Age-Related Differences in Vancomycin-Associated Nephrotoxicity and Efficacy in Methicillin-Resistant Staphylococcus aureus Infection: A Comparative Study between Elderly and Adult Patients.

Elderly patients (age ≥ 65 years) are susceptible to methicillin-resistant Staphylococcus aureus (MRSA) infections, with potential for more adverse treatment outcomes or complications compared to younger adults (18-64 years). This study compared vancomycin-associated nephrotoxicity and efficacy in elderly and adult patients and investigated the correlation between vancomycin pharmacokinetic/pharmacodynamic (PK/PD) indices and clinical outcomes. A prospective study was conducted in 10 hospitals in Shanghai from October 2012 to November 2019. A total of 164 patients with MRSA infections were enrolled, including 83 elderly and 81 adult patients. Vancomycin therapeutic drug monitoring (TDM) was performed in all patients, indicating significantly higher vancomycin trough concentrations (Ctrough), 24-h area under the curve (AUC24) values, and AUC24/minimum inhibitory concentration (AUC24/MIC) values in elderly patients compared to adult patients. The incidence of vancomycin-associated nephrotoxicity was nearly three times higher in elderly patients (18.1% vs. 6.2%, p = 0.020), despite similar clinical and microbiological efficacy. Of particular importance, a Ctrough > 20 mg/L was found as an independent factor of nephrotoxicity in elderly patients. Further analysis of patients with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 also revealed that elderly patients had significantly higher vancomycin-related PK/PD indices and more nephrotoxicity than adult patients. In conclusion, elderly patients receiving vancomycin therapy face a higher risk of nephrotoxicity, which requires close vancomycin TDM, especially when the Ctrough exceeds 20 mg/L.

Regional delivery of mesothelin-targeted chimeric antigen receptor T-cell effectively and safely targets colorectal cancer liver metastases in mice.

Background: Liver metastasis is the major cause of colorectal cancer related death. Mesothelin (MSLN)-targeted chimeric antigen receptor (CAR) T-cell therapy has been illustrated effective and safe through regional delivery of breast cancer, ovarian cancer and malignant mesothelioma tumors. Herein, we investigated the safety, efficacy, and immune microenvironment of regional delivery of MSLN (CAR) T-cell in the treatment of colorectal carcinoma liver metastases (CRLM). Methods: Second-generation MSLN CAR T-cells were administered by portal vein (PV) or caudal vein (CV, systemic administration) delivery in an orthotopic MSLN+ CRLM nonobese diabetic (NOD)/severe combined immunodeficient (SCID)/γc-/- (NSG) mouse model. A total of 20 mice were randomly divided into control group, non-transduced T cell (NT)-CV group, NT-PV group, MSLN CAR T-cell CV (MSLN-CV) group, and MSLN CAR T-cell PV (MSLN-PV) group, with each group containing four mice to examine the safety and efficacy. The bioluminescence intensity (BLI) of tumor burden, tumor tissue macroscopic and microscopic observation were used to evaluate treatment efficacy. The safety was examined by body weight, survival time, and vital organ damage of mice. CAR T-cell infiltration and cytokine concentration were analyzed by flow cytometry, and immunostaining. The change of immune microenvironment between regional delivery and systemic delivery was investigated on an immune reconstructed CRLM patient-derived xenograft (PDX) model. Additionally, T cell subsets and immunosuppressive markers were examined. Results: PV administration of 1×107/100 µL MSLN CAR T-cells in 20 NSG mice was well tolerated, and no overt toxicity was observed. The tumor burden in the PV group was obviously alleviated. The BLI was (0.73±0.52)×109 in PV group and (1.97±0.11)×109 in CV group (P<0.05), CD8+ granzyme B (GB)+ T cell percentage (MSLN-CV 4.42%±0.47% vs. MSLN-PV 13.5%±4.67%, P<0.01) and cytokine concentration were obviously increased in the MSLN-PV group. In the immune reconstituted CRLM PDX model, intratumor (IT) delivery of MSLN CAR T-cells exhibited much more infiltration of CD4+ and CD8+ T cells accompanied with elevated expression levels of PD-1, LAG-3, and TIM-3. Conclusions: Regional delivery of MSLN-targeted CAR T-cell therapy has encouraging results in the orthotopic CRLM NSG mouse model and PDX model, and converts the tumor microenvironment from cold to hot. This study may provide a new therapeutic approach for CRLM. Further clinical study is needed.

CBCT-based three-dimensional dual-phase vascular image fusion: a novel technique for interventional real-time TIPS guidance.

BACKGROUND: Due to the invisibility of the portal vein (PV), how to puncture the PV accurately and safely in transjugular intrahepatic portosystemic shunt (TIPS) creation remains a challenge of the procedure. OBJECTIVES: We aimed to provide the first evaluation of the safety, feasibility, and efficiency of cone beam computed tomography (CBCT)-based three-dimensional (3D) dual-phase vascular image fusion for interventional real-time guided PV puncture during TIPS procedures. MATERIALS AND METHODS: From January 2021 to May 2021, 13 patients undergoing TIPS were prospectively enrolled in this study. Images of the hepatic artery (HA) and PV in 3D were acquired and overlaid on interventional fluoroscopy images in a dual-phase display mode for real-time PV puncture guidance. The number of PV puncture attempts, puncture time, overlaid image accuracy, dose area product, fluoroscopy time, and interventional complications were recorded. RESULTS: Portal vein puncture guided by CBCT-based 3D dual-phase vascular image fusion was successfully performed on 92.3% (12/13) patients. The mean number of PV puncture attempts was 1.8 ± 0.7 (1-3). The mean puncture time and fluoroscopy time was 3.5 ± 1.2 (2-6) min and 25.1 ± 9.4 (15-45) min, respectively. The mean dose area product was 39.49 ± 7.88 (28.81-52.87) mGym2. The error between the reference position of the fusion image and the interventional PV angiography image was less than 0.5 cm. No interventional complication was observed. CONCLUSION: Our results show that 3D dual-phase vascular image fusion might be a safe and feasible technique for interventional real-time guided PV puncture during TIPS. This novel technique might help to reduce the number of PV puncture attempts and the puncture time as well as lower the risks of interventional complications.

Surufatinib plus toripalimab in patients with advanced neuroendocrine tumours and neuroendocrine carcinomas: An open-label, single-arm, multi-cohort phase II trial.

BACKGROUND: The programmed death 1 inhibitor toripalimab plus the angio-immuno kinase inhibitor surufatinib revealed a tolerable safety profile and preliminary efficacy in patients with advanced solid tumours in a phase I study. PATIENTS AND METHODS: This was an open-label, single-arm, multi-cohort phase II study in China. Patients with advanced neuroendocrine tumours (NETs) or neuroendocrine carcinomas (NECs) or mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) who had failed or were intolerable of standard treatment were given surufatinib (250 mg orally, once daily) plus toripalimab (240 mg intravenously, once every 3 weeks). Primary end-point was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end-points included duration of response (DoR), disease control rate, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Forty patients were enrolled into two cohorts by tumour types (NET, n = 19; NEC-MiNEN, n = 21). ORRs (95% CIs) were 21.1% (6.1-45.6) and 23.8% (8.2-47.2) in the NET and NEC-MiNEN cohorts, respectively. Median DoR was 7.1 months (6.9-not evaluable [NE]) and 4.1 months (3.0-NE), respectively. Median PFS was 9.6 months (4.1-NE) and 4.1 months (1.5-5.5); median OS was 27.3 (15.3-NE) and 10.9 months (9.1-14.6), respectively. Overall, grade ≥ 3 treatment-related adverse events occurred in 18 (45.0%) patients. CONCLUSIONS: Surufatinib plus toripalimab showed antitumour activity and a tolerable safety profile in patients with previously treated NETs/NECs/MiNENs. Further study of this combination regimen is ongoing for advanced NECs, for which current therapeutic options remain limited. CLINICALTRIALS: gov: NCT04169672.

Hypoxia-activated cascade nanovaccine for synergistic chemoembolization-immune therapy of hepatocellular carcinoma.

In this work, a promising treatment strategy for triggering robust antitumor immune responses in transarterial chemoembolization of hepatocellular carcinoma (HCC) is presented. The zeolitic imidazolate framework nanoparticles loaded with hypoxia-activated prodrug tirapazamine and immune adjuvant resiquimod facilitated in situ generation of nanovaccine via a facile approach. The nanovaccine can strengthen the ability of killing the liver cancer cells under hypoxic environment, while was capable of improving immunogenic tumor microenvironment and triggering strong antitumor immune responses by increasing the primary and distant intratumoral infiltration of immune cells such as cytotoxic T cells. Moreover, a porous microcarrier, approved by FDA as pharmaceutical excipient, was designed to achieve safe and effective delivery of the nanovaccine via transarterial therapy in rabbit orthotopic VX2 liver cancer model. The microcarrier exhibited the characteristics of excellent drug loading and occlusion of peripheral artery. The collaborative delivery of the microcarrier and nanovaccine demonstrated an exciting inhibitory effect on solid tumors and tumor metastases, which provided a great potential as novel combination therapy for HCC interventional therapy.

Endovascular management of sinistral portal hypertension-related variceal hemorrhage: a multicenter retrospective study.

PURPOSE: This study aimed to assess the safety and efficacy of endovascular managements, including splenic vein recanalization (SVR), partial splenic embolization (PSE), and percutaneous transsplenic gastric varices embolization combined with PSE (PSE+GVE), for management of SPH-related variceal hemorrhage (VH). METHODS: A total of 61 patients with SPH-related VH from three hospitals were enrolled and classified into three groups: the SVR group (Group 1, n=24), the PSE+GVE group (Group 2, n=17), and the PSE group (Group 3, n=20). Baseline characteristics and clinical outcomes were compared among the groups. RESULTS: The technical success rates for transhepatic and transsplenic SVR were 27.8% and 34.6%, respectively. No major complications were observed during any of the procedures. The median follow-up period was 53.2 months. The 2-year GI rebleeding rates for Group 1, 2, and 3 were 0%, 5.9%, and 35%, respectively. Groups 1 and 2 have a lower GI rebleeding rate (p = 0.002, p = 0.048, respectively) and better results of the degree of GV (p = 0.003, p = 0.044, respectively) compared to Group 3. No significant differences were found in 2-year GI rebleeding rates and the degree of GV between Group 1 and 2 (p = 0.415, p = 0.352, respectively). CONCLUSION: SVR, PSE+GVE, and PSE seem safe and effective for management of SPH-related VH. SVR appears to be the superior treatment option. Transsplenic access may further increase the SVR success rate. PSE+GVE seems to have comparable outcomes in GV control and GI rebleeding rates compared to SVR, while superior to PSE.

Unraveling the serial glycosylation in the biosynthesis of steroidal saponins in the medicinal plant Paris polyphylla and their antifungal action.

Sugar-sugar glycosyltransferases play important roles in constructing complex and bioactive saponins. Here, we characterized a series of UDP-glycosyltransferases responsible for biosynthesizing the branched sugar chain of bioactive steroidal saponins from a widely known medicinal plant Paris polyphylla var. yunnanensis. Among them, a 2'-O-rhamnosyltransferase and three 6'-O-glucosyltrasferases catalyzed a cascade of glycosylation to produce steroidal diglycosides and triglycosides, respectively. These UDP-glycosyltransferases showed astonishing substrate promiscuity, resulting in the generation of a panel of 24 terpenoid glycosides including 15 previously undescribed compounds. A mutant library containing 44 variants was constructed based on the identification of critical residues by molecular docking simulations and protein model alignments, and a mutant UGT91AH1Y187A with increased catalytic efficiency was obtained. The steroidal saponins exhibited remarkable antifungal activity against four widespread strains of human pathogenic fungi attributed to ergosterol-dependent damage of fungal cell membranes, and 2'-O-rhamnosylation appeared to correlate with strong antifungal effects. The findings elucidated the biosynthetic machinery for their production of steroidal saponins and revealed their potential as new antifungal agents.

Effects of HepaSphere microsphere encapsule epirubicin with a new loading method transarterial chemoembolization: in vitro and in vivo experiments.

METHODS: HS microspheres were loaded in a solution of hypertonic saline and contrast medium at different ratios. Morphology, size distribution, and drug loading capacity of the microsphere were evaluated. Rabbits with hepatic VX2 tumors underwent conventional TACE, drug-eluting beads TACE with HS microsphere loading epirubicin by recommended method (dTACE) or a new loading method (ndTACE). The plasma and tissue epirubicin concentration, tumor necrosis, and the microsphere distribution within the tumor were assessed. RESULTS: It was found that the mean diameter of HS microspheres was effectively reduced to 102 ± 14 µm after loading with 10.0% NaCl and Ultravist (370 mg I /mL) at a ratio of 2: 8 ml. The loading capacity reached 78.7%. It was noted that the concentration of tumor epirubicin was significantly higher (p = 0.016) in the ndTACE group (11,989.8 ± 5776.6 ng/g) than the concentration in the dTACE (6516.5 ± 3682.3 ng/g) and in cTACE groups (1564.1 ± 696.1 ng/g, p < 0.001). Further, the tumor necrosis in group with the new loading method (ndTACE) was 92.4%. CONCLUSIONS: The size of HS microsphere can be effectively reduced when it is loaded with a mixture of hypertonic saline and non-ionic contrast material. HS microsphere loaded with epirubicin using the new method (ndTACE) can increase the drug concentration in tumor and hence exert better improved antitumor effect.

Effects of orthodontic treatment on masticatory muscles activity: a meta-analysis.

Context: A comprehensive meta-analysis was carried out to investigate the impact of orthodontics on masticatory muscles.Methods: A thorough search of various databases, including CNKI, Wan Fang, VIP, CBM, MEDLINE, PubMed, Cochrane Library, EMBASE, Web of Science, and Google Scholar, was performed to identify relevant studies on patients undergoing orthodontics or functional corrections. Six case-control studies were finally included in this analysis, which specifically examined the effect of orthodontic treatment on masticatory muscle function.Results: The results revealed that the mean masticatory muscle voltage in patients treated with orthodontics was found to be higher after treatment compared to before treatment [odds ratio (OR)=1.57, 95% confidence interval (CI) (0.57, 2.57), p = 0.002], which could potentially have an impact on masticatory muscle function, particularly in individuals with Class II Division 1 malocclusion.Conclusion: These findings contribute to our understanding of the effects of orthodontic interventions on masticatory muscles, further highlighting the importance of orthodontics in optimising masticatory function.

Microwave ablation combined with transarterial chemoembolization containing doxorubicin hydrochloride liposome for treating primary and metastatic liver cancers.

Aims: To determine the safety and efficacy of microwave ablation (MWA) and transarterial chemoembolization (TACE) with doxorubicin hydrochloride liposome (DHL) in patients with primary liver cancer (PLC) and metastatic liver cancer (MLC). Materials and methods: The medical records of patients with primary or metastatic liver cancer who underwent MWA combined with TACE containing DHL from March 2019 to March 2022 were collected and analyzed. Treatment-related adverse events (AEs) were recorded. Local tumor response was evaluated according to the modified RECIST criteria. Local tumor progression-free survival (LTPFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: Altogether, 96 patients with liver cancer were included (PLC, n â€‹= â€‹45; MLC, n â€‹= â€‹51). Forty (41.7%) patients experienced AEs during treatment, and eight (8.3%) patients developed grade 3 AEs. Compared to before treatment, the serum total bilirubin level and neutrophil to lymphocyte ratio significantly increased after treatment. The median LTPFS was 14.5 months in patients with PLC and 10.7 months in patients with MLC. The median OS was not reached in patients with PLC or MLC. The 1-month and 3-month disease control rates reached more than 80% in both groups. Conclusion: MWA combined with TACE with DHL may be a safe and effective method for the treatment of liver cancer.

Comparative efficacy of vancomycin in treating ST5 and ST764 methicillin-resistant Staphylococcus aureus infections in adult patients.

IMPORTANCE: Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium that is resistant to multiple drugs and can cause serious infections. In recent years, one of the most widespread strains of MRSA worldwide has been the clonal complex 5 (CC5) type. Sequence type 5 (ST5) and ST764 are two prevalent CC5 strains. Although ST5 and ST764 are genotypically identical, ST764 is classified as a hybrid variant of ST5 with characteristics of community-associated MRSA (CA-MRSA). In contrast to ST5, ST764 lacks the tst and sec genes but carries the staphylococcal enterotoxin B (seb) gene. Vancomycin is commonly used as the first-line treatment for MRSA infections. However, it is currently unclear whether the genetic differences between the ST5 and ST764 strains have any impact on the efficacy of vancomycin in treating MRSA infections. We conducted a prospective observational study comparing the efficacy of vancomycin against ST5-MRSA and ST764-MRSA in five hospitals in China. There were significant differences in bacteriological efficacy between the two groups, with virulence genes, such as the tst gene, being a risk factor for bacterial persistence (adjusted odds ratio, 4.509; 95% confidence interval, 1.216 to 16.724; P = 0.024). In the future, it may be necessary to consider personalized vancomycin treatment strategies based on the genetic characteristics of MRSA isolates.

Comparison of intraluminal brachytherapy combined with and without stent placement for treatment of obstructive jaundice induced by tumor thrombus.

PURPOSE: To compare the safety and efficacy of intraluminal brachytherapy with iodine-125 (125I) seed strand implantation combined with and without stent placement to treat patients with obstructive jaundice induced by tumor thrombus. METHODS: Between January 2018 and June 2022, 42 patients with malignant obstructive jaundice (MOJ) induced by tumor thrombus were included. 20 patients received 125I seed strand implantation and stent placement (group A). The remaining 22 patients, implanted 125I seed strands only, served as control (group B). The two groups' overall survival and jaundice-free survival were compared using the Kaplan-Meier method and log-rank test. RESULTS: During the follow-up period, the mean survival time of group A was 38.0 ± 4.1 months (95%CI, 30.0-46.1 months), while that of group B was 25.1 ± 2.8 (95% CI, 19.5-30.6 months) (p = 0.406). The mean survival rates of 12 months for all patients, group A, and group B was 66.7%, 65%, and 68%, respectively. The mean jaundice-free survival of group A and group B were 34.0 ± 3.6 months (95% CI, 27.9-41.2months) and 22.9 ± 2.7 months (95%CI, 17.5-28.2months) (p = 0.254), respectively. Two PTBD drainage tube infection cases occurred in group A and group B separately. CONCLUSIONS: 125I intraluminal brachytherapy is an effective and safe therapy for treating patients with obstructive jaundice induced by tumor thrombus.

Defensive furofuran lignans localized to the oil cells of Neocinnamomum delavayi and their metabolism by a specialist insect.

Neocinnamomum delavayi (Lauraceae) leaves with abundant oil cells are seldom attacked by insects, but their chemical constituent and biological function remain obscure. Three furofuran lignans, including (+)-eudesmin (3), (+)-magnolin (4), and demethoxyaschantin (5), were identified to be the major specialized metabolites in the oil cells of N. delavayi leaves through laser microdissection coupled with NMR analysis. Compounds 3 and 4 exhibited obvious antifeedant activity against a generalist insect Spodoptera exigua, and their natural contents in the leaves could effectively defend against generalist insects. Intriguingly, three specific metabolites 9-11, the O-demethylation derivates of compounds 3-5, were identified from a native specialist insect Dindica polyphaenaria feeding with N. delavayi leaves, implying an adaptation mechanism of specialist insects to plant defensive compounds. The results revealed a chemical connection between plants and insects, which would contribute to our understanding of plant-insect interaction and insect management.

The influence of shunting left/right portal vein branch on post-TIPS hepatic encephalopathy: a study protocol for multicenter randomized blinded controlled trial.

INTRODUCTION: Gastroesophageal varices (GOV) bleeding is a common and serious complication of advanced liver cirrhosis with a median survival of less than 2 years. Multiple guidelines have pointed out that transjugular intrahepatic portosystemic shunt (TIPS) is the rescue treatment of acute variceal hemorrhage (AVB) after failure of standard therapy and an effective second-line treatment for preventing patients with high risks from rebleeding of GOV. The safety and stability of TIPS have been greatly improved due to the improvements of related technologies and the emergence of various novel devices, but the incidence of hepatic encephalopathy (HE) after shunting (10-50%) hindered the widespread use of TIPS. The target portal vein branch might affect the incidence of HE after TIPS. The aim of this study is to compare the rate of HE in patients with hepatitis B virus (HBV) related cirrhosis receiving TIPS either the left or right branch of the portal vein with 8mm Viatorr stent for preventing rebleeding from GOV. METHODS AND ANALYSIS: This study is a multicenter randomized controlled trial comparing the influence of shunting left or right portal vein branch on post-TIPS hepatic encephalopathy for preventing rebleeding from GOV in patients with HBV-related cirrhosis. A total of 130 patients will be recruited over a period of 24 months across 5 centers in China. Eligible patients will be stratified 1:1 to constructing either a left or right portal vein shunt with an 8-mm Viatorr stent. The primary objective was to compare the incidence of post-TIPS hepatic encephalopathy between the two groups. The secondary objectives were to compare the grade and duration of hepatic encephalopathy, the rate of shunt dysfunction, the rate of variceal rebleeding, the HE-free survival, the cumulative patency rate of the stent, and the overall survival at 12 months and 24 months between two groups. ETHICS AND DISSEMINATION: This study was approved by the ethics committee of Zhongshan Hospital of Fudan University (No. B2018-292R) and was registered at ClinicalTrials.gov (NCT03825848). All participants give written informed consent. TRIAL REGISTRATION: ClinicalTrials.gov NCT03825848. Registered on January 31, 2019 TRIAL STATUS: The first patient was recruited into our study on June 19, 2019. A total of 55 patients were recruited till May 27, 2021 (27 and 28 patients assigned to shunting the left (L Group) and right (R Group) branches of the portal vein, respectively).

Three-dimensional-printed MPBI@ß-TCP scaffold promotes bone regeneration and impedes osteosarcoma under near-infrared laser irradiation.

Beta-tricalcium phosphate (ß-TCP) is considered as one of the most promising biomaterials for bone reconstruction. This study generated a functional molybdenum disulfide (MoS2 )/polydopamine (PDA)/-bone morphogenetic protein 2 (BMP2)-insulin-like growth factor-1 (IGF-1) coating on the ß-TCP scaffold and analyzed the outcomes. The MoS2 /PDA-BMP2-IGF-1@ß-TCP (MPBI@ß-TCP) scaffold was prepared by 3D printing and physical adsorption, followed by characterization to validate its successful construction. The in vitro osteogenic effect of the MPBI@ß-TCP scaffold was evaluated. It was found that MPBI@ß-TCP augmented the adhesion, diffusion and proliferation of mesenchymal stem cells (MSCs). The alkaline phosphatase (ALP) activity, collagen secretion and extracellular matrix (ECM) mineralization along with the expression of Runx2, ALP and OCN were also enhanced in the presence of MPBI@ß-TCP. Additionally, MPBI@ß-TCP stimulated endothelial cells to secrete VEGF and promoted capillary-like tubule formation. We then confirmed the biocompatibility of MPBI@ß-TCP to macrophages and its anti-inflammatory effects. Furthermore, under near-infrared (NIR) laser irradiation, MPBI@ß-TCP produced photothermal effect to not only kill MG-63 osteosarcoma cells, but also enhance bone regeneration in vivo with biosafety. Overall, this work demonstrates that 3D-printed MPBI@ß-TCP with enhanced osteogenic activity under NIR laser irradiation has a vast potential in the field of tissue defects.

The prognostic role of the AST/ALT ratio in hepatocellular carcinoma patients receiving thermal ablation combined with simultaneous TACE.

BACKGROUND: To evaluate the prognostic value of the pre-treatment aspartate transaminase (AST)/alanine transaminase (ALT) ratio in hepatocellular carcinoma (HCC) patients receiving radiofrequency ablation (RFA)/microwave ablation (MWA) combined with simultaneous TACE. METHODS: The data for 117 patients were retrospectively analyzed in this study. The endpoint of prognosis was overall survival (OS). The Youden index was used to choose the optimal cut-off value of the pre-treatment AST/ALT ratio for OS prediction. Univariate and multivariate analyses were used to identify independent risk factors, then integrated to establish the nomogram. RESULTS: The AST/ALT ratio cut-off value for OS prediction was 0.89, and patients with a higher AST/ALT ratio had poorer OS. The median OS for the high-value AST/ALT group was not reached, while the median OS for the low-value AST/ALT group was 48.5 months (P = 0.0047). The univariate and multivariate analysis showed that AST/ALT ratio, AFP, and tumor numbers were independent prognostic indicators for OS. The integrated nomogram showed higher predictive accuracy for OS (C-index 0.674, 95%CI: 0.600-0.748). CONCLUSIONS: The preoperative AST/ALT ratio could be a prognostic indicator for HCC patients receiving thermal ablation combined with simultaneous TACE.

Comparing the predictive ability of portoatrial and portocaval gradient after transjugular intrahepatic portosystemic shunt creation for variceal rebleeding.

BACKGROUND: Measuring the portal pressure gradient from the portal vein (PV) to the inferior vena cava (IVC) or to the right atrium (RA) remains controversial. The aim of our study was to compare the predictive ability of portoatrial gradient (PAG) and portocaval gradient (PCG) for variceal rebleeding. METHODS: The data of 285 cirrhotic patients with variceal bleeding undergoing elective transjugular intrahepatic portosystemic shunt (TIPS) in our hospital were analyzed retrospectively. The variceal rebleeding rates were compared between groups categorized by established or modified thresholds. The median follow-up time was 30.0 months. RESULTS: After TIPS, PAG was equal to (n = 115) or more than (n = 170) PCG. The pressure of IVC was defined as an independent predictor for a PAG-PCG difference of ≥ 2 mmHg (p < 0.001, OR 1.23, 95% CI 1.10-1.37). Using a threshold of 12 mmHg, PAG (p = 0.081, HR 0.63, 95% CI 0.37-1.06) could not predict variceal rebleeding but PCG could (p = 0.003, HR 0.45, 95% CI 0.26-0.77). This pattern was unchanged when a ≥ 50% reduction from baseline was also considered as a threshold (PAG/PCG: p = 0.114 and 0.001). Subgroup analyses showed that only in patients with post-TIPS IVC pressure < 9 mmHg (p = 0.018), PAG could predict variceal rebleeding. Because PAG was on average 1.4 mmHg higher than PCG, patients were classified by a PAG of 14 mmHg, and there was no difference in rebleeding rates between these two groups (p = 0.574). CONCLUSIONS: For patients with variceal bleeding, the predictive ability of PAG is limited. The portal pressure gradient should be measured between the PV and IVC.

Predictive power of portal pressure gradient remeasured shortly after transjugular intrahepatic portosystemic shunt.

BACKGROUND AND AIMS: The portal pressure gradient (PPG) measured at the time of transjugular intrahepatic portosystemic shunt (TIPS) completion (immediate PPG) is easily disturbed by many factors. This study aimed to assess the diagnostic value of PPG remeasured 2-4 days after TIPS (delayed PPG) by comparison with immediate PPG. METHODS: We retrospectively analyzed cirrhotic patients aged 18-75 years who received TIPS for preventing variceal rebleeding and pressure measurements at different time points. RESULTS: Of 154 eligible patients, 60 (39.0%), 62 (40.3%), and 32 (20.8%) were categorized into group LL (both immediate and delayed PPG < 12 mmHg), LH (immediate PPG < but delayed PPG ≥ 12 mmHg) and HH (both immediate and delayed PPG ≥ 12 mmHg), respectively. Mean immediate and delayed PPG were 9.2 mmHg and 12.8 mmHg (p < 0.001). During a median follow-up of 22 months, the 1-year probability of variceal rebleeding was significantly lower in group LL (1.7%) compared to LH (9.8%, absolute risk difference [ARD]: - 8.2%, p = 0.028) and HH (12.6%, ARD: - 11.1%, p = 0.014), but was not significantly different between groups LH and HH (ARD: - 2.9%, p = 0.671). Delayed PPG (p < 0.001) was identified as an independent predictor of variceal rebleeding in multivariable Cox regression analysis. The area under curves of delayed and immediate PPG in predicting variceal rebleeding were 0.837 and 0.693 for all patients (p = 0.031), and 0.936 and 0.694 for patients without shunt dysfunction (p < 0.001). CONCLUSIONS: In cirrhotic patients with variceal bleeding, delayed PPG has higher predictive power for variceal rebleeding than immediate PPG.

Chemical investigation of Buddleja officinalis leaves and localization of defensive triterpenoids to its glandular trichomes.

Buddleja officinalis is a traditional Chinese medicinal plant covered with glandular and non-glandular trichomes on leaves. Phytochemical investigation of its leaves led to the identification of one undescribed tetranorcycloartane 3-oxo-25,26,27,29-tetranorcycloartan-24-oic acid (1) and one first identified natural product tetranorcycloartane 3-oxo-25,26,27,29-tetranorcycloartan-24-oic methyl ester (2), along with an undescribed megastigmane glucoside (3) and 14 known constituents (4-17). Structures of undescribed chemicals were elucidated by comprehensive 1D and 2D NMR, MS and CD analysis. Further chemical investigation resulted in six triterpenoids (4-9) being localized to the trichomes of B. officinalis. The major trichome components cycloeucalenone (4) and 24-oxo-29-norcycloartan-3-one (5) showed potent antifeedant activity against a generalist insect cotton bollworm (Helicoverpa armigera), but no obvious activity against the specialist herbivore Hyphasis inconstans. Compounds 4 and 7 also displayed inhibitory effects on seed germination of Arabidopsis thaliana. In addition, 1 and 4 exhibited moderate antibacterial activity toward three gram-positive bacteria.