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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Mesenchymal Stem Cell-Derived Exosomes Ameliorate Delayed Neurocognitive Recovery in Aged Mice by Inhibiting Hippocampus Ferroptosis via Activating SIRT1/Nrf2/HO-1 Signaling Pathway.

Delayed neurocognitive recovery (dNCR) is a prevalent perioperative neurological complication in older patients and has common characteristics such as acute cognitive dysfunction, impaired memory, and inattention. Mesenchymal stem cell-derived exosomes (MSCs-Exo) are enclosed by a lipid bilayer contain proteins, DNA, miRNA, and other components, which are important mediators of intercellular communication. It has been reported that exosomes could play an important role in the treatment of neurodegenerative diseases, nerve injury, and other neurological diseases. In this study, we examined the effects of MSCs-Exo on dNCR aged mice after exploratory laparotomy and evaluated their potential regulatory mechanisms. We found that MSCs-Exo treatment ameliorated cognitive impairment in dNCR aged mice. MSCs-Exo inhibit hippocampus ferroptosis and increase the expression of silent information regulator 1 (SIRT1), factor nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in dNCR aged mice. Interestingly, the above effects of MSCs-Exo on dNCR aged mice were abolished by SIRT1 selective inhibitor EX-527. In conclusion, these findings indicated that MSCs-Exo can ameliorate cognitive impairment by inhibiting hippocampus ferroptosis in dNCR aged mice via activating SIRT1/Nrf2/HO-1 signaling pathway, providing a potential avenue for the treatment of dNCR.

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.

Insights into the removal of organic contaminants by calcium sulfite activation with Fe(III): Performance, kinetics, and mechanisms.

S(IV)-based advanced oxidation process has been applied for contaminants remediation. However, as a traditional source of sulfite (SO32-), Na2SO3 is extremely soluble in water, resulting in a high concentration of SO32- to quench the generated reactive oxygen species (ROS). In this work, CaSO3 was introduced instead of Na2SO3 for its slow-released SO32- ability and Fe(III)/CaSO3 system was established for the removal of trichloroethylene (TCE) and other organic contaminants. The degradation efficiency of TCE reached 94.0% and TCE could be completely dechlorinated and mineralized, while the removal of other contaminants was all over 85.0% at the optimal tested conditions. Through EPR detection, ROS scavenging and probe tests, and quantification of ROS amounts, it was concluded that the dominant ROS in Fe(III)/CaSO3 system were SO4-· and 1O2, of which the transformation mechanism of SO4-· to 1O2 was revealed and demonstrated comprehensively. The synergistic contaminants degradation performance in different sulfur-iron-containing systems and in the presence of oxidants was evaluated. The effects of various solution conditions were assessed and Fe(III)/CaSO3 system was of higher resistance on complex solution matrixes, suggesting the broad-spectrum and application perspective for the remediation of complex contaminants in actual water.

Female genital tuberculosis presented with primary infertility and persistent CA-125 elevation: A case report.

Introduction: and importance: Tuberculosis is one of the leading causes of mortality in many developing countries. Female genital tuberculosis, a relatively uncommon form of tuberculosis, is critically challenging to diagnose due to its insidious and non-typical presentations. Case presentation: Herein, we present with an asymptomatic infertile woman with persistently high CA-125 passed undiagnosed until laparoscopy unveiled the diagnosis of TB. Clinical discussion: In this study, we highlight the diagnostic complexities in female genital tuberculosis and demonstrate the value of the CA-125 increase in prompting the suspicion of tuberculosis in the appropriate clinical context. Conclusion: Given the considerably large number of individuals with tuberculosis in China, we strongly recommend routine tuberculosis screening in women seeking infertility care in China.

CRISPR-Cas14a-integrated strand displacement amplification for rapid and isothermal detection of cholangiocarcinoma associated circulating microRNAs.

Circulating microRNAs (miRNA) can serve as key biomarkers for early diagnose of cholangiocarcinoma. Herein, an assay that uses circulating miRNA to trigger strand displacement amplification (SDA) and a CRISPR-Cas14a system to report the SDA process has been developed. In the proposed method, SDA directly amplifies miRNAs without reverse transcription. The reporter, CRISPR-Cas14a, can reduce the risks of non-specific amplification and offers a sequential amplification that improves the sensitivity for miRNA detection. The assay, termed Cas14SDA, can discriminate miRNAs with similar sequences and can detect as low as 680 fM miR-21 (miRNAs overexpressed in cholangiocarcinoma) within 1 h. In particular, Cas14a was efficiently activated by a single-stranded SDA amplicon which improved the sensitivity by 2.86 times compared to that using Cas12a. This research has demonstrated that the Cas14SDA assay can discriminate cholangiocarcinoma patients from healthy donors by testing miR-21 in their blood samples. The Cas14SDA assay developed broadens the toolbox for miRNA biomarker analysis.

Insights into the role of nanoscale zero-valent iron in Fenton oxidation and its application in naphthalene degradation from water and slurry systems.

Few researches have focused on the role of nanoscale zero-valent iron (nZVI) in Fenton-like process for polycyclic aromatic hydrocarbons (PAHs) removal. In this study, the naphthalene (NAP) degradation tests in ultrapure water showed that nZVI addition could enhance NAP degradation from 79.7% to 99.0% in hydrogen peroxide (H2 O2 )/Fe (II)/nZVI/NAP system at the molar ratio of 10/5/3/1, showing the excellent role of nZVI in promoting NAP removal. Multiple linear regression analysis found that the correlation coefficient between H2 O2 consumption and NAP degradation was converted from -9.17 to 0.48 with nZVI and 1-mM H2 O2 , indicating that nZVI could decompose H2 O2 more beneficially for NAP degradation. Multiple Fe (II)-dosing and iron leaching tests revealed that nZVI could gently liberate Fe (II) and promote Fe (II)/Fe (III) redox cycle to enhance the NAP degradation. When the H2 O2 /Fe (II)/nZVI/NAP molar ratios of 10/5/3/1 and 50/25/15/1 were applied in the simulated NAP contaminated actual groundwater and soil slurry, respectively, 75.0% and 82.9% of NAP removals were achieved. Based on the major degradation intermediates detected by GC/MS, such as 1,4-naphthalenedione, cinnamaldehyde, and o-phthalaldehyde, three possible NAP degradation pathways were proposed. This study provided the applicable potential of nZVI in Fenton process for PAHs contaminated groundwater and soil remediation. PRACTITIONER POINTS: nZVI enhanced the NAP degradation in Fenton-like process. Three schemes of NAP degradation pathway were proposed. nZVI performed well in the remediation of the simulated NAP contamination.

TSPO Ligands Protect against Neuronal Damage Mediated by LPS-Induced BV-2 Microglia Activation.

Neuroinflammation is a critical pathological process of neurodegenerative diseases, and alleviating the inflammatory response caused by abnormally activated microglia might be valuable for treatment. The 18 kDa translocator protein (TSPO), a biomarker of neuroinflammation, is significantly elevated in activated microglia. However, the role of TSPO in microglia activation has not been well demonstrated. In this study, we evaluated the role of TSPO and its ligands PK11195 and Midazolam in LPS-activated BV-2 microglia cells involving mitophagy process and the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation. In the microglia-neuron coculture system, the neurotoxicity induced by LPS-activated microglia and the neuroprotective effects of PK11195 and Midazolam were evaluated. Our results showed that after being stimulated by LPS, the expression of TSPO was increased, and the process of mitophagy was inhibited in BV-2 microglia cells. Inhibition of mitophagy was reversed by pretreatment with PK11195 and Midazolam. And the NLRP3 inflammasome was increased in LPS-activated BV-2 microglia cells in the microglia-neuron coculture system; pretreatment with PK11195 and Midazolam limited this undesirable situation. Lastly, PK11195 and Midazolam improved the cell viability and reduced apoptosis of neuronal cells in the microglia-neuron coculture system. Taken together, TSPO ligands PK11195 and Midazolam showed neuroprotective effects by reducing the inflammatory response of LPS-activated microglia, which may be related to the enhancement of mitophagy and the inhibition of NLRP3 inflammasome.

A meta-analysis comparing hepatic arterial infusion chemotherapy and sorafenib for advanced hepatocellular carcinoma.

Background: The majority of patients with hepatocellular carcinoma (HCC) are diagnosed in an advanced stage. Although sorafenib is recommended as the standard treatment for advanced HCC, its efficacy is limited. In some studies, hepatic arterial infusion chemotherapy has demonstrated a significant therapeutic benefit for advanced HCC compared with sorafenib. We systematically evaluated and compared the efficacy and safety of hepatic arterial infusion chemotherapy and sorafenib for advanced HCC. Methods: A systematic search of PubMed, Embase, Web of Science and the Cochrane Library up to December 31, 2020 was conducted. Study outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse effects. The hazard ratio and odds ratio with 95% confidence intervals (CI) were used to measure the pooled effect. Results: Eighteen retrospective or prospective cohort studies and one prospective controlled study were included, with 1,339 patients treated with hepatic arterial infusion chemotherapy (HAIC) and 1,060 patients treated with sorafenib. We found that hepatic arterial infusion chemotherapy was superior to sorafenib in terms of OS [hazard ratio (HR): 0.66, 95% CI: 0.46-0.95, P=0.027], PFS (HR: 0.55, 95% CI: 0.44-0.69, P<0.001), ORR [assessed using Response Evaluation Criteria in Solid Tumors (RECIST): OR: 9.02, 95% CI: 6.01-13.53, P<0.001; assessed using modified RECIST: odds ratio (OR): 3.71, 95% CI: 1.92-7.16, P<0.001], and DCR (assessed using RECIST: OR: 2.31, 95% CI: 1.40-3.83, P=0.001; assessed by modified RECIST: OR: 2.28, 95% CI: 1.22-4.28, P=0.01). Dermatological adverse effects and hypertension were significantly higher in the sorafenib group for all grades of adverse effects. However, regarding severe adverse effects, hepatic arterial infusion chemotherapy was associated with more frequent leukocytopenia and thrombocytopenia. Conclusions: Hepatic arterial infusion chemotherapy demonstrated favorable efficacy and safety for advanced HCC compared with sorafenib and should be recommended for suitable patients with advanced HCC.