Do atrophic gastritis and intestinal metaplasia reverse after Helicobacter pylori eradication?

BACKGROUND: It's still controversial whether Helicobacter pylori (H. pylori) eradication can reverse atrophic gastritis (AG) and intestinal metaplasia (IM). Therefore, we performed a meta-analysis to estimate the effect of H. pylori eradication on AG and IM. METHODS: We searched the PubMed, Web of Science and EMBASE datasets through April 2023 for epidemiological studies, which provided mean glandular atrophy (GA) or IM score before and after H. pylori eradication, or provided ORs, RRs or HRs and 95% CIs for the association of AG or IM with H. pylori eradication. Weighted mean difference (WMD) and pooled ORs and 95%CIs were used to estimate the effect of H. pylori eradication on AG and IM. RESULTS: Twenty articles with a total of 5242 participants were included in this meta-analysis. H. pylori eradication significantly decreased GA score in the antrum (WMD -0.36; 95% CI: -0.52, -0.19, p < 0.01), GA score in the corpus (WMD -0.35; 95% CI: -0.52, -0.19, p < 0.01), IM score in the antrum (WMD -0.16; 95% CI: -0.26, -0.07, p < 0.01) and IM score in the corpus (WMD -0.20; 95% CI: -0.37, -0.04, p = 0.01). H. pylori eradication significantly improved AG (pooled OR 2.96; 95% CI: 1.70, 5.14, p < 0.01) and IM (pooled OR 2.41; 95% CI: 1.24, 4.70, p < 0.01). The association remained significant in the subgroup analyses by study design, sites of lesions, regions and follow-up time. Although Publication bias was observed for AG, the association remained significant after trim-and-fill adjustment. CONCLUSIONS: H. pylori eradication could significantly improve AG and IM at early stage.

Prognostic value of pretreatment lymphocyte percentage in oral cancer: A prospective cohort study.

OBJECTIVE: To assess the prognostic role of pretreatment lymphocyte percentage (LY%) for patients with oral squamous cell carcinoma (OSCC). METHODS: A large-scale prospective cohort study between July 2002 and March 2021 was conducted. Propensity score-matched (PSM) analysis and inverse probability of treatment weighting (IPTW) analysis were performed to adjust for potential confounders. Using random survival forest (RSF), the relative importance of pretreatment LY% in prognosis prediction was also assessed. RESULTS: A total of 743 patients were enrolled and followed up (median: 2.75 years, interquartile range: 1.25-4.42 years). A high pretreatment LY% was significantly associated with better disease-specific survival of patients with OSCC (Hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.42, 0.84). The same tendency was observed in PSM (HR = 0.57, 95% CI: 0.38, 0.85) and IPTW analysis (HR = 0.57, 95% CI: 0.40, 0.82). RSF showed that LY% ranked the fifth among importance ranking of all prognostic factors. CONCLUSION: Pretreatment LY% showed a moderate predictive ability, suggesting it might be a valuable tool to predict prognosis for patients with OSCC.

Development and validation of a model for the prediction of disease-specific survival in patients with oral squamous cell carcinoma: based on random survival forest analysis.

OBJECTIVE: To establish a model for predicting the disease-specific survival (DSS) of patients with oral squamous cell carcinoma (OSCC). METHODS: Patients diagnosed with OSCC from the Surveillance, Epidemiology, and End Results (SEER) database were enrolled and randomly divided into development (n = 14,495) and internal validation cohort (n = 9625). Additionally, a cohort from a hospital located in Southeastern China was utilized for external validation (n = 582). RESULTS: TNM stage, adjuvant treatment, surgery, tumor sites, age, grade, and gender were used for RSF model construction based on the development cohort. The effectiveness of the model was confirmed through time-dependent ROC curves in different cohorts. The risk score exhibited an almost exponential increase in the hazard ratio of death due to OSCC. In development, internal, and external validation cohorts, the prognosis was significantly worse for patients in groups with higher risk scores (all log-rank P < 0.05). CONCLUSION: Based on RSF, a high-performance prediction model for OSCC prognosis was created and verified in this study.

Translocator Protein 18 kDa (TSPO) as a Novel Therapeutic Target for Chronic Pain.

Chronic pain is an enormous modern public health problem, with significant numbers of people debilitated by chronic pain from a variety of etiologies. Translocator protein 18 kDa (TSPO) was discovered in 1977 as a peripheral benzodiazepine receptor. It is a five transmembrane domain protein, mainly localized in the outer mitochondrial membrane. Recent and increasing studies have found changes in TSPO and its ligands in various chronic pain models. Reversing their expressions has been shown to alleviate chronic pain in these models, illustrating the effects of TSPO and its ligands. Herein, we review recent evidence and the mechanisms of TSPO in the development of chronic pain associated with peripheral nerve injury, spinal cord injury, cancer, and inflammatory responses. The cumulative evidence indicates that TSPO-based therapy may become an alternative strategy for treating chronic pain.

Sulforaphane inhibits blue light-induced inflammation and apoptosis by upregulating the SIRT1/PGC-1α/Nrf2 pathway and autophagy in retinal pigment epithelial cells.

The present study elucidated mechanisms through which sulforaphane (SFN) protects retinal pigment epithelial (RPE) cells from blue light-induced impairment. SFN could activate the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increase the expression of the heme oxygenease-1 (HO-1) gene and production of glutathione. SFN reduced blue light-induced oxidative stress, and effectively activated cytoprotective components including Nrf-2, HO-1, thioredoxin-1, and glutathione. The protective effect of SFN on blue light-induced injury was blocked by the Nrf2 inhibitor ML385, suggesting that the SFN-induced Nrf2 pathway is involved in the cytoprotective effect of SFN. SFN inhibited intercellular adhesion molecule-1 expression induced by TNF-α or blue light, suggesting the anti-inflammatory activity of SFN. The inhibitory effect of SFN was associated with the blocking of NF-κB p65 nuclear translocation in blue light-exposed RPE cells. SFN protected RPE cells from blue light-induced interruption of the mitochondrial membrane potential and reduction of the Bcl-2/Bax ratio and cleaved caspase-3 and PARP-1 expression, suggesting the antiapoptotic activity of SFN. SFN alone or together with blue light exposure increased the expression of the autophagy-related proteins LC3BII and p62. An autophagy inhibitor, 3-MA, inhibited the protective effect of SFN on blue light-induced cell damage. SFN increased sirtuin-1 (SIRT1) expression; however, treatment with blue light induced peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) expression. Our study results demonstrated that SFN exerts its protective effect under blue light exposure by maintaining the Nrf2-related redox state and upregulating SIRT1 and PGC-1α expression and autophagy.

Endovascular Repair of Spontaneous Iliac Vein Rupture.

Spontaneous iliac vein rupture is a relatively rare but fatal disease. Herein, 2 cases are reported. The two middle-aged and elderly females complaining of abdominal pain were admitted without any history of trauma. The computed tomography image both showed one huge hematoma in the lower abdominal cavity and the left external iliac venous thrombus. Venogram showed ruptures of the left external iliac vein and stenosis of the left common iliac vein after percutaneous mechanical thrombectomy. Stent grafts were implanted by endovascular technique. Favorable outcomes were achieved in both cases.

Effects of dialysis modality choice on the survival of end-stage renal disease patients in southern China: a retrospective cohort study.

BACKGROUND: The optimal choice of treatment, with hemodialysis (HD) or peritoneal dialysis (PD), for end-stage renal disease (ESRD) patients, is still controversial. Only a few studies comparing HD and PD have been conducted in China, which has the largest number of dialysis patients in the world. METHODS: A retrospective cohort study was conducted on ESRD patients who began renal replacement treatment from January 1, 2012 to December 31, 2017 in Guangdong Provincial Hospital of Chinese Medicine. Propensity scoring match was applied to balance the baseline conditions and multivariate Cox regression analysis to compare the mortality between HD and PD patients, and evaluated the correlation between mortality and various baseline characteristics. RESULTS: A total of 436 HD patients and 501 PD patients were included in this study, and PD patients had better survival than HD patients, but the difference was not statistically significant. For younger ESRD patients (≤60-year-old), the overall survival of PD was better than that of HD, but HD was associated with a lower risk of death in older patients (> 70-year-old). This difference was still significant after adjustment for a variety of confounding factors. Female gender, age at dialysis initiation, cardiovascular disease, cholesterol, and HD were risk factors of all-cause mortality in the younger subgroup, while PD was risk factor in the older subgroup. CONCLUSION: PD may be a better choice for younger ESRD patients, and HD for the older patients.

Enhancement of benzene degradation by persulfate oxidation: synergistic effect by nanoscale zero-valent iron (nZVI) and thermal activation.

The feasibility of an advanced oxidation process based upon sodium persulfate (SPS) activated simultaneously by heat (50 °C) and nanoscale zero-valent iron (nZVI) on benzene removal was investigated. The experimental results strongly showed the synergistic effect of thermal and nZVI activation to SPS and benzene removal was enhanced with the increase of SPS/nZVI/benzene molar ratio. Specifically, 94% of benzene could be removed in 1 hr at 50 °C at the SPS/nZVI/benzene molar ratio of 10/5/1. The radical scavenger tests and electron paramagnetic resonance (EPR) analysis confirmed that SO4•- was the predominant species contributing to benzene degradation. Further, the effects of the solution matrix on benzene elimination were investigated. The results indicated that benzene destruction in the thermally activated SPS/nZVI system performed better under acidic conditions, and the high concentration of both Cl- and HCO3 - had adverse effects on benzene elimination. The test for the performance of benzene degradation in the actual groundwater demonstrated that benzene could be degraded entirely at SPS/nZVI/benzene molar ratio of 40/40/1 at 50 °C, indicating that the synergistic catalysis of thermal and nZVI activation to SPS is exploitable and the thermally activated SPS/nZVI system can be applicable to the remediation of benzene contaminated groundwater.

Fermented soymilk and soy and cow milk mixture, supplemented with orange peel fiber or Tremella flava fermented powder as prebiotics for high exopolysaccharide-producing Lactobacillus pentosus SLC 13.

BACKGROUND: A high exopolysaccharide-producing Lactobacillus pentosus SLC 13 strain was isolated from mustard pickles and showed the characteristics of a probiotic. Orange peel fiber powder (OPFP) and Tremella flava fermented powder (TFP) were shown to be potential prebiotics for L. pentosus SLC 13. The present study aimed to further develop new symbiotic fermented lactic acid beverages using SLC 13 with different proportions of cow milk and soymilk as food substrates, as well as with OPFP or TFP as prebiotics. RESULTS: Acidification rate (soymilk groups, 3.02-4.37 mU min-1 ; soymilk/milk mixture groups, 1.33-2.84 mU min-1 ) and fermentation time (soymilk groups, 7.09-9.25 h; soymilk/milk mixture groups, 12.51-27.34 h) indicated that soymilk represents a suitable substrate for SLC 13-mediated fermentation. Moreover, OPFP and TFP induced a higher exopolysaccharide production of SLC 13 and a higher water holding capacity of fermented beverages. Sensory evaluations suggested that soymilk groups fermented with 10 g kg-1 OPFP (SF-1.0P) and that with 5 g kg-1 TFP (SF-0.5T) and also soymilk/milk mixture groups fermented with 5 g kg-1 OPFP (HSMF-0.5P) and that with 10 g kg-1 TFP (HSMF-1.0T) represent potential fermented drinks. Additionally, SF-1.0P and SF-0.5T products could be preserved for at least 21 days at 4 °C, with high viable cell counts (> 8.8 log10 CFU mL-1 ) and water holding capacity. CONCLUSION: In the present study, we developed SF-1.0P and SF-0.5T products as a new symbiotic fermented lactic acid beverages. However, in the future, consumer acceptability could be improved by properly regulating the ratio of sugar to acid or seasoning. © 2019 Society of Chemical Industry.

The cold-inducible RNA-binding protein-Thioredoxin 1 pathway ameliorates mitochondrial dysfunction and mitochondrial dynamin-related protein 1 level in the hippocampus of aged mice with perioperative neurocognitive dysfunction.

BACKGROUND: As a multi-disease model, neuroinflammation, mitochondrial dysfunction, and oxidative stress might be involved in the pathogenic process of perioperative neurocognitive dysfunction (PND). Dynamin-related protein 1 (Drp1) could mediate mitochondrial fission and play important roles in mitochondrial dynamic homeostasis and mitochondria function. The Drp1 may be involved in PND development. The cold-inducible RNA-binding protein (Cirbp) could bind to the 3'-UTR of the thioredoxin 1 (Trx1) mRNA, control oxidative stress, and improve mitochondrial function. In this study, we hypothesized that the Cirbp-Trx1 pathway could ameliorate mitochondrial dysfunction and Drp1 levels in PND mice. METHODS: Differentially expressed genes were screened using the Gene Expression Omnibus (GEO) database GSE95426 and validated using PCR. Eighteen-month-old C57BL/6 mice were subjected to tibial fracture surgery to generate a PND model. Cirbp was upregulated by hippocampal stereotaxic injections of over-Cirbp plasmid according to the manufacturer's instructions for the in vivo DNA transfection reagent. Cirbp expression was measured using western blot (WB) and immunofluorescence (IF). The Morris water maze (MWM) was used to assess cognitive function. After behavioral testing, the hippocampal tissue was extracted to examine changes in mitochondrial Drp1, mitochondrial function, neuroinflammation, and oxidative stress. RESULTS: Differential gene screening showed that Cirbp expression was significantly downregulated (fold change >1.5, p = 0.003272) in the PND model. In this study, we also found that Cirbp protein levels were downregulated, accompanied by an impairment of cognition, a decrease in superoxide dismutase (SOD) activity, and an increase in malondialdehyde (MDA) content, mitochondrial Drp1 levels, neuroinflammation, and apoptosis. Cirbp overexpression increased Trx1 protein levels and reversed the damage. However, this protective effect was abolished by PX-12 treatment with a Trx1 inhibitor. CONCLUSIONS: The Cirbp-Trx1 pathway may regulate mitochondrial dysfunction and mitochondrial Drp1 expression in the hippocampus of PND mice to ameliorate cognitive dysfunction.

Three-dimensional treatment-planning-based prediction of seed migration to chest after 125I seed brachytherapy for hepatic malignancy.

PURPOSE: To develop and validate risk models incorporating clinical and/or imaging parameters based on three-dimensional treatment-planning systems (3D-TPS) to predict the occurrence of 125I seed migration and the number of migrated seeds <2/≥2 to the chest after brachytherapy for patients with malignant hepatic tumors. METHODS AND MATERIALS: A total of 480 patients diagnosed with malignant liver tumors receiving 125I seed brachytherapy from July 2010 to May 2020 were retrospectively enrolled. Variables included 3D-TPS-based CT parameters, that is, the distance from the seed to the inferior vena cava (DSI), the distance from the seed to the second hepatic portal (DSP) and the angle from the seed to the second hepatic portal (ASP), and patients' clinical characteristics, that is, the number of seed implantation procedures (NSP), the maximum number of implanted seeds one time (MAX) and laboratory parameters within 1 week before treatment. Two sets of logistic regression models incorporating clinical and/or imaging variables were developed to predict the occurrence of seed migration and the number of migrated seeds <2/≥2. Model performance was assessed by ROC analysis and decision curve analysis. RESULTS: Compared with the clinical models, the combined model showed a higher discriminative ability for both the prediction of migration occurrence and number of migrated seeds ≥ 2/<2 to the chest (AUC, 0.879 vs. 0.668, p < 0.05; 0.895 vs. 0.701, p < 0.05). The decision curve analysis results indicated higher net benefits of combined models than clinical models. Variables, including DSI, NSP and pretreatment lymphocyte-to-neutrophil ratio, acted as the most important predictors in combined models. CONCLUSIONS: The proposed combined models based on 3D-TPS improved discriminative abilities for predicting 125I seed migration and number of migrated seeds <2/≥2 to the chest after hepatic brachytherapy, being promising to aid clinical decision-making.

Transcatheter arterial chemoembolisation combined with lenvatinib plus camrelizumab as conversion therapy for unresectable hepatocellular carcinoma: a single-arm, multicentre, prospective study.

Background: The synergistic effect of locoregional therapy in combination with systemic therapy as a conversion therapy for unresectable hepatocellular carcinoma (uHCC) is unclear. The purpose of this study was to evaluate the efficacy and safety of transcatheter arterial chemoembolisation (TACE) combined with lenvatinib and camrelizumab (TACE + LEN + CAM) as conversion therapy for uHCC. Methods: This single-arm, multicentre, prospective study was conducted at nine hospitals in China. Patients (aged 18-75 years) diagnosed with uHCC, an Eastern Cooperative Oncology Group performance score (ECOG-PS) of 0-1 and Child-Pugh class A received camrelizumab (200 mg, every 3 weeks) and lenvatinib (bodyweight ≥60 kg: 12 mg/day; <60 kg: 8 mg/day) after TACE treatment. Surgery was performed after tumour was assessed as meeting the criteria for resection. Patients who did not meet the criteria for surgery continued to receive triple therapy until disease progression or intolerable toxicity. Primary endpoints were objective response rate (ORR) according to the modified Response Evaluation Criteria in Solid Tumours (mRECIST) and safety. Secondary endpoints included the surgical conversion rate, radical (R0) resection rate, and disease control rate (DCR). This study was registered with Chinese Clinical Trial Registry (ChiCTR2100050410). Findings: Between Oct 25, 2021, and July 20, 2022, 55 patients were enrolled. As of the data cutoff on June 1, 2023, the median follow-up was 13.3 months (IQR 10.6-15.9 months). The best tumour response to triple therapy was complete response (CR) in 9 (16.4%) patients, partial response (PR) in 33 (60.0%) patients, stable disease (SD) in 5 (9.1%) patients, or progressive disease (PD) in 7 (12.7%) patients. The ORR was 76.4% (42/55, 95% CI, 65.2-87.6%), and the DCR was 85.5% (47/55, 95% CI, 76.2-94.8%) per mRECIST. Twenty-four (43.6%) of the 55 patients suffered from grade 3-4 treatment-related adverse events (TRAEs). No grade 5 TRAEs occurred. A total of 30 (30/55, 54.5%) patients were converted to resectable HCC and 29 (29/55, 52.7%) patients underwent resection. The R0 resection rate was 96.6% (28/29). The major pathologic response (MPR) and pathologic complete response (pCR) rates in the surgery population were 65.5% (19/29) and 20.7% (6/29), respectively. Only one patient developed a Clavien-Dindo IIIa complication (abdominal infection). No Clavien-Dindo IIIb-V complications occurred. The median OS and median PFS were not reached. Interpretation: The triple therapy (TACE + LEN + CAM) is promising active for uHCC with a manageable safety. Moreover, triple therapy has good conversion efficiency and the surgery after conversion therapy is feasible and safe. To elucidate whether patients with uHCC accepting surgical treatment after the triple therapy can achieve better survival benefits than those who receive triple therapy only, well-designed randomised controlled trials are needed. Funding: This study was funded by the Natural Science Foundation of Fujian Province, China (2022J01691) and the Youth Foundation of Fujian Province Health Science and Technology Project, China (2022QNA035).

Application of Guglielmi detachable coils in embolization of iatrogenic renal hemorrhage.

BACKGROUND: This study aims to evaluate the application value of Guglielmi detachable coils (GDCs) in the embolization of iatrogenic renal hemorrhage. METHODS: Twelve iatrogenic renal hemorrhage patients who failed conservative treatment were randomly treated by superselective transcatheter arterial embolization (TAE) with GDCs, gelatin sponge, and microcoil embolization, respectively. The efficacy of treatment, damage to renal function, and renal infarct size were observed. RESULTS: Embolizations were successful in all patients on the first attempt. Hematuria disappeared completely after the surgery; no recurrence of hemorrhage and no abnormal renal function were observed during the follow-up period. Postoperative angiography revealed that patients treated with GDC embolization had minimum renal infarcts. CONCLUSIONS: In summary, while superselective TAE provides a safe and effective therapy in patients with iatrogenic renal hemorrhage, the application of GDCs can better prevent the loss of normal renal tissue after embolization.

Characteristics of historical precipitation for winter wheat cropping in the semi-arid and semi-humid area.

Winter wheat (Triticum aestivum L.) is one of major crops in the area along Huai river, China where it is a semi-arid and semi-humid region with sufficient precipitation for an entire season, but with uneven distribution within various growth stages. The instability of precipitation is an important factor in limiting wheat production potential under climate change. Therefore, it is essential to characterise the precipitation associated with different crop developmental stages. Based on climate data from 1999 to 2020 in six representative meteorological stations, we characterised the historical precipitation relating to seven key growth stages in winter wheat. There is no clear trend of interannual variation of precipitation for wheat season, with an average of precipitation of 414.4 ± 121.2 mm. In terms of the distribution of precipitation grade within a season, light rain was dominant. Continuous rain occurred frequently during the pre-winter seedling and overwintering stages. The critical period of water demand, such as jointing and booting, has less precipitation. The fluctuation range of precipitation in sowing, heading-filling and maturation stages is large, which means that there is flood and drought at times. In conclusion, these findings provide a foundation for instructing winter wheat cropping in confronting with waterlogging and drought risk due to uneven precipitation in 'Yanhuai' region, China.

Crop/Plant Modeling Supports Plant Breeding: II. Guidance of Functional Plant Phenotyping for Trait Discovery.

Observable morphological traits are widely employed in plant phenotyping for breeding use, which are often the external phenotypes driven by a chain of functional actions in plants. Identifying and phenotyping inherently functional traits for crop improvement toward high yields or adaptation to harsh environments remains a major challenge. Prediction of whole-plant performance in functional-structural plant models (FSPMs) is driven by plant growth algorithms based on organ scale wrapped up with micro-environments. In particular, the models are flexible for scaling down or up through specific functions at the organ nexus, allowing the prediction of crop system behaviors from the genome to the field. As such, by virtue of FSPMs, model parameters that determine organogenesis, development, biomass production, allocation, and morphogenesis from a molecular to the whole plant level can be profiled systematically and made readily available for phenotyping. FSPMs can provide rich functional traits representing biological regulatory mechanisms at various scales in a dynamic system, e.g., Rubisco carboxylation rate, mesophyll conductance, specific leaf nitrogen, radiation use efficiency, and source-sink ratio apart from morphological traits. High-throughput phenotyping such traits is also discussed, which provides an unprecedented opportunity to evolve FSPMs. This will accelerate the co-evolution of FSPMs and plant phenomics, and thus improving breeding efficiency. To expand the great promise of FSPMs in crop science, FSPMs still need more effort in multiscale, mechanistic, reproductive organ, and root system modeling. In summary, this study demonstrates that FSPMs are invaluable tools in guiding functional trait phenotyping at various scales and can thus provide abundant functional targets for phenotyping toward crop improvement.

Comparative studies of organic contaminant removal in different calcium sulfite-enhanced oxidant/Fe(II) systems: Kinetics, mechanisms, and differentiated degradation pathways.

The application of S(IV) for the regeneration of Fe(II) has been widely investigated. As the common S(IV) sources, sodium sulfite (Na2SO3) and sodium bisulfite (NaHSO3) are soluble in the solution, resulting in excessive SO32- concentration and redundant radical scavenging problems. In this research, calcium sulfite (CaSO3) was applied as the substitution for the enhancement of different oxidant/Fe(II) systems. The advantages of CaSO3 could be summarized as follows: (1) it could sustainedly supplement SO32- for Fe(II) regeneration, preventing radical scavenging and unnecessary reagent waste; (2) the cost and toxicity of CaSO3 were extremely lower than that of other S(IV) sources; (3) the concentration of reactive species increased in the presence of CaSO3; and (4) after the reaction, SO42- would form CaSO4 precipitate, which would not increase the burden of SO42- in the solution. In the participation of CaSO3, the removal of trichloroethylene (TCE) and other organic contaminants were significantly promoted and different enhanced systems had high tolerance on complex solution conditions. The major reactive species in different systems were determined through qualitative and quantitative analyses. Eventually, the dechlorination and mineralization of TCE were measured and the differentiated degradation pathways in different CaSO3-enhanced oxidants/Fe(II) systems were elucidated.

Efficacy and safety of hepatic artery infusion chemotherapy combined with tyrosine kinase inhibitors plus programmed death-1 inhibitors for hepatocellular carcinoma refractory to transarterial chemoembolization.

Background: The subsequent therapy for hepatocellular carcinoma (HCC) patients with refractory to transarterial chemoembolization (TACE) is still controversial. This study was performed to evaluate the efficacy and safety of combination therapy comprising hepatic artery infusion chemotherapy (HAIC), lenvatinib, and programmed death-1 inhibitors relative to HAIC combined with lenvatinib. Methods: In this single-center retrospective study, we analyzed data from HCC patients with refractory to TACE from June 2017 to July 2022. Primary study outcomes were overall survival (OS) and progression-free survival (PFS), while the secondary outcomes were the objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events. Results: We enrolled 149 patients finally, including 75 patients who received HAIC combined with lenvatinib plus PD-1 inhibitors therapy (HAIC+L+P group) and 74 patients who received HAIC combined with lenvatinib therapy (HAIC+L group). The median OS in the HAIC+L+P group (16.0; 95% CI: 13.6~18.3 months) was significantly higher compared to the HAIC+L group (9.0; 95% CI: 6.5~11.4 months) (p = 0.002), while the median PFS in the HAIC+L+P group (11.0; 95% CI: 8.6~13.3 months) was significantly higher compared to the HAIC+L group (6.0; 95% CI: 5.0~6.9 months) (p < 0.001). Significant between-group differences in DCR (p = 0.027) were found. Additionally, 48 pairs of patients were matched after propensity matching analysis. The survival prognosis between two groups before propensity matching is similar to that after propensity matching. Moreover, the percentage of patients with hypertension in the HAIC+L+P group was significantly higher compared to the HAIC+L group (28.00% vs. 13.51%; p = 0.029). Conclusions: A combination therapy of HAIC, lenvatinib, and programmed death-1 inhibitors significantly improved oncologic response and prolonged survival duration, showing a better survival prognosis for HCC patients with refractory toTACE.

Clinical Complete Response After Conversion Therapy for Unresectable Hepatocellular Carcinoma: Is Salvage Hepatectomy Necessary?

Background: This study aimed to determine whether salvage hepatectomy offers prognostic advantages for unresectable hepatocellular carcinoma (uHCC) patients with clinical complete response (cCR) after conversion therapy. Methods: A total of 74 consecutive uHCC patients with cCR after conversion therapy at seven major cancer centers in China between October 2018 and December 2021 were included. One-to-one propensity score matching (PSM) was performed to minimize the influence of potential confounders. Disease-free survival (DFS) and overall survival (OS) rates were compared between the surgical group and the non-surgical group. Results: Before PSM, 45 patients received salvage hepatectomy, and 29 patients received nonsurgical treatment. The 1-, 2-, and 3-year DFS rates were 77.8%, 61.5%, and 61.5% in the surgical group and 81.2%, 60.9%, and 60.9% in the non-surgical group, respectively. The 1-, 2-, and 3-year OS rates were 92.9%, 92.9%, and 69.7% in the surgical group and 100%, 70%, and 70% in the non-surgical group, respectively. There were no statistical differences in DFS and OS between groups [hazard ratio (HR)=0.715, 95% confidence interval (CI): 0.250-2.043, p=0.531; HR=0.980, 95% CI: 0.177-5.418, p=0.982, respectively]. After PSM, 26 pairs of patents were selected; there remained no significant differences in DFS and OS between these two groups (HR=1.547, 95% CI: 0.512-4.669, p=0.439; HR=1.024, 95% CI: 0.168-6.242, p=0.979, respectively). Conclusion: Through the study, it tend to show that salvage hepatectomy may be not essential for uHCC patients with cCR, especially for patients with a high risk of surgical complications. Prospective trials with long term follow-up are warranted to evaluate this treatment option.

Anti-inflammatory and analgesic effects of Streblus indicus.

The bark of Streblus indicus, a Dai medicine in China, has been listed in the Chinese Materia Medica as possessing hemostatic and analgesic properties. Ethnic medicine books record that its bark or leaves for the treatment of mumps and lymphoma. However, according to the literature survey, anti-inflammatory and analgesic studies available for leaves and branches of S. indicus have been seldom reported so far. The current study focuses on the metabolites of S. indicus bark and leaves responsible for anti-inflammatory and analgesic effects on the basis of bioactive-included acetic acid writhing, hot-plate, and xylene-induced ear swelling. The secretion of inflammatory mediators, TNF-α, IL-6, IL-1ß, IL-4, and IL-10, were evaluated for their anti-inflammatory by xylene-induced in mouse ear cells. Histological examination was used to assess the anti-inflammatory and analgesic effects of the branches and leaves of S. indicus, and Western blot analysis determined the mechanism of the methanolic extract of branches and leaves. Different metabolites of S. indicus significantly alleviated analgesic and anti-inflammatory effects, with no discernable differences among them. All metabolites decreased the levels of TNF-α, IL-1ß, and IL-6 and increased the levels of IL-4 and IL-10. The analgesic and anti-inflammatory mechanism of the methanolic extract was related to the NF-kB signaling pathway. These results not only would account for scientific knowledge for the traditional application of S. indicus, but also provide a credible theoretical foundation for the further development of anti-inflammatory and analgesic agents.

Transarterial Chemoembolization Plus Lenvatinib and PD-1 Inhibitors for Hepatocellular Carcinoma with Main Trunk Portal Vein Tumor Thrombus: A Multicenter Retrospective Study.

Purpose: In recent years, immune checkpoint inhibitors have been used in combination with tyrosine kinase inhibitors and local therapies, creating a new era in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, the benefits of this triple therapy remain unclear. Thus, this study evaluated whether the combination of transarterial chemoembolization (TACE), lenvatinib, and programmed death-1 (PD-1) inhibitors (triple therapy) was effective and safe for unresectable HCC with main trunk portal vein tumor thrombus (Vp4). Patients and Methods: This study enrolled patients receiving triple therapy at four institutions between August 2018 and April 2022. Patient characteristics and course of treatment were extracted from patient records. Tumors and tumor thrombus response were evaluated using an HCC-specific modified RECIST. Kaplan-Meier curve analysis demonstrated overall survival (OS) and progression-free survival (PFS). Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Results: Median follow-up duration was 18 (4.0-26.3) months. Overall, 41 patients with HCC and Vp4 receiving first-line triple therapy were enrolled. The intrahepatic tumor objective response rate was 68.3%. The median OS was 21.7 (range, 2.8-30.5) months, whereas the median PFS was 14.5 (range, 1.3-27.6) months. Twelve patients received sequential resections. Resection was independently associated with favorable OS and PFS. Fever (31.7%), hypertension (26.8%), fatigue (24.4%), abnormal liver function (63.4%) and decreased appetite (21.9%) were the AEs frequently associated with treatment. No treatment-related mortality occurred. Conclusion: TACE plus lenvatinib and PD-1 inhibition was effective and tolerable for treating unresectable HCC with Vp4, with a high tumor response rate and favorable prognosis.