Effectiveness of direct needle puncture for complete hepaticojejunostomy anastomotic stricture after pancreaticoduodenectomy (with video).

A 79-year-old Japanese woman, who had undergone pancreaticoduodenectomy 6 months prior to presentation owing to pancreatic cancer, complained of jaundice with high fever. Computed tomography revealed proximal bile duct dilatation with complete hepaticojejunostomy anastomotic stricture (HJAS). We performed a single-balloon endoscopy for biliary drainage. The presence of a scar-like feature surrounding the anastomosis was identified as the HJAS. White-light imaging during single-balloon endoscopy revealed that the HJAS contained a milky whitish area (MWA), suggesting that a membranous and fibrosis layer affected continuous inflammation around the center of the anastomosis (within a scar-like feature). Endoscopic dilatation was performed using an endoscopic injection needle, with the MWA used as an indicator. A 23-gauge endoscopic injection needle was used to penetrate the center of the blind lumen within the MWA, and a pinhole was created in the stricture. After confirming the position of the proximal bile duct using a contrast medium with the needle, an endoscopic guidewire with a cannula was inserted into the pinhole. A through-the-scope sequential balloon dilator was used to dilate the stricture, and a plastic stent was inserted into the proximal bile duct. This endoscopic intervention led to positive outcomes. In cases of complete HJAS occlusion, an endoscopic approach to the bile duct is difficult because the anastomotic opening of the HJAS is not visible. Thus, puncturing within the MWA, which can be used as a scar-like landmark within a complete membranous HJAS, is considered a useful endoscopic strategy.

Trabecular Meshwork Regeneration for Glaucoma Treatment Using Stem Cell-Derived Trophic Factors.

Glaucoma is one of the leading causes of irreversible blindness. Stem cell therapy has shown promise in the treatment of primary open-angle glaucoma in animal models. Stem cell-free therapy using stem cell-derived trophic factors might be in demand in patients with high-risk conditions or religious restrictions. In this chapter, we describe methods for trabecular meshwork stem cell (TMSC) cultivation, secretome harvesting, and protein isolation, as well as assays to ensure the health of TMSC post-secretome harvesting and for secretome periocular injection into mice for therapeutic purposes.

Short pulse grid and subthreshold micropulse laser (the sandwich grid) plus intravitreal ranibizumab for the treatment of diabetic macular edema.

OBJECTIVE: To investigate the effects of two laser treatment procedures combined, short pulse grid laser (SP) and subthreshold micropulse laser (MP) (the sandwich grid [SWG] technique), plus intravitreal ranibizumab (IVR) on central subfield thickness (CSFT), best-corrected visual acuity (BCVA) and macular sensitivity in patients with diabetic macular edema (DME). METHODS: Forty-five eyes (of 33 patients) with center-involving DME were treated with the SWG laser technique plus IVR and followed for 12 months. Laser treatment was performed at baseline: SP laser spots were placed in a grid pattern in the macular area (500 µm from the fovea) according to the extension of DME; subsequently, MP laser was delivered up to the edge of the fovea. MP laser re-treatment sessions could be performed every 3 months if DME was present and CSFT was ≥ 300 µm on SD-OCT. IVR injection was performed at baseline and repeated monthly if CSFT > 300µm. Preoperatively and monthly, ophthalmological examination was performed including measurements of BCVA, CSFT, and macular sensitivity. RESULTS: One-year follow-up data is available for 37 eyes of 27 patients. Mean ± SE CSFT (µm) was 509.36 ± 25.14 and 325.76 ± 15.34 at baseline and 12 months, respectively. A significant reduction in mean CSFT was observed at all study visits compared to baseline (p < 0.001). Mean ± SE BCVA (logMAR) was 0.62 ± 0.04 and 0.45 ± 0.04 at baseline and 12 months, respectively. A significant improvement in mean BCVA was observed at all study visits compared to baseline (p < 0.001). Mean ± SE macular sensitivity (dB) was 17.85 ± 0.80 and improved to 19.05 ± 0.59 after one year of follow-up (p = 0.006). The mean number of IVR injections was 8.29 ± 0.63. The mean number of MP laser procedures including the initial SWG laser session was 3.67 ± 0.22. No ocular or systemic adverse effects were observed. CONCLUSION: The SWG laser technique plus IVR was associated with significant improvement in macular edema, BCVA, and macular sensitivity in patients with center-involving DME. CLINICAL TRIAL NUMBER (CAAE): 22969019.4.0000.5440.

A simple cell proliferation assay and the inflammatory protein content show significant differences in human plasmas from young and old subjects.

Some studies showed a "rejuvenating" effect of exposing aging tissues to a young environment. In mouse heterochronic parabiosis experiments, in response to young organisms, old animals lived longer than isochrony old age-matched conjoint animals. Comparable "rejuvenating" effects were obtained by injecting young plasma in old mice. This raised great hopes of slowing down the senescence process in humans by the injection of young plasma, as well as to prevent or cure age-related diseases. Some clinical trials are currently being performed or were recently completed. However, these studies are small and of limited duration, and we still lack convincing evidence to support the effectiveness of young plasma injection. It is urgent to perform additional investigations, including the development of an assay to measure the cell proliferation induction capability of different human plasmas, before one can seriously think of a large-scale treatment of humans. We adopted a simple method to measure the potential of different plasmas in supporting cell line proliferation, regardless of the co-presence of a platelet lysate. By comparing plasmas from young and old subjects, we observed a decreased activity in plasmas from old individuals. The young plasma effect may be attributed to specific proteins and growth factors more abundant in younger individuals that could decrease with age. Alternatively, or at the same time, the reduced cell proliferation support could be due to inhibitors present in the old plasma. Studying the different protein content of young and old plasmas was out of the scope of this article. Such differences should be adequately investigated by proteomics using many samples. However, a preliminary study of the different protein content of young and old plasmas was part of the assay validation using a commercially available cytokine array for parallel determination of the relative levels of 105 selected human proteins. We could show the existence of specific differences between young and old plasmas and that plasmas from old individuals presented a higher concentration of "inflammatory" proteins.

Redefining hemorrhoid therapy with endoscopic polidocanol foam sclerobanding.

Hemorrhoids are a common and painful condition, with conventional treatments such as endoscopic rubber band ligation (ERBL) and injection sclerotherapy often falling short due to high recurrence rates and significant post-operative pain. A clinical trial by Qu et al introduces a novel approach called endoscopic poli-docanol foam sclerobanding (EFSB). This multicenter randomized trial involved 195 patients with grade II and III internal hemorrhoids and demonstrated that EFSB significantly reduced recurrence rates and post-procedural pain while improving symptom relief and patient satisfaction compared to ERBL. The study's strengths include its robust design, comprehensive outcome evaluation, and patient-centered approach. Despite limitations such as the single-blind design and relatively short follow-up period, the findings suggest that EFSB could enhance clinical practice by offering a more effective and patient-friendly treatment option. Further research is needed to validate these results and explore the long-term benefits and cost-effectiveness of EFSB.

Effect of Danhong injection on pharmacokinetics and pharmacodynamics of rivaroxaban in rats.

BACKGROUND AND OBJECTIVES: Rivaroxaban is often used in combination with DHI to treat thromboembolic disease. Whether the combination causing HDIs is still unknown. The purpose of this study was to evaluate effects of DHI on pharmacokinetics and pharmacodynamics of rivaroxaban in rats and effects on CYP3A2. METHODS: Plasma concentration of rivaroxaban with or without DHI was determined by HPLC. Pharmacokinetics parameters were calculated. Effect of DHI on pharmacodynamics of rivaroxaban was investigated by APTT, PT, TT, FIB, INR, length of tail thrombosis, vWF, t-PA, PAI-1, IL-1ß, TNF-α and histopathological sections. Effect of DHI on CYP3A2 in rats was investigated by probe drug method. RESULTS: Cmax and AUC of rivaroxaban increased significantly in combination group (P < 0.05). APTT, PT, INR and TT increased (P < 0.05), length of tail thrombosis, FIB, vWF, PAI-1, IL-1ß and TNF-α of combination group decreased significantly (P < 0.05) compared with rivaroxaban or DHI alone. Histopathologic section of tail thrombus had significant improvement. Cmax and AUC of dapsone increased (P < 0.05) in DHI group. CONCLUSION: In summary, DHI is an inhibitor of CYP3A2 and could significantly affect pharmacokinetics and pharmacodynamic of rivaroxaban, enhance anticoagulant and antithrombotic efficacy in rats. However, the combination of rivaroxaban and DHI might lead to potential HDIs. The dosage of rivaroxaban should be adjusted in clinical.

Repeated intrathecal injections of peripheral nerve-derived stem cell spheroids improve outcomes in a rat model of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide. However, existing treatments still face numerous clinical challenges. Building on our prior research showing peripheral nerve-derived stem cell (PNSC) spheroids with Schwann cell-like phenotypes can secrete neurotrophic factors to aid in neural tissue regeneration, we hypothesized that repeated intrathecal injections of PNSC spheroids would improve the delivery of neurotrophic factors, thereby facilitating the restoration of neurological function and brain tissue repair post-TBI. METHODS: We generated PNSC spheroids from human peripheral nerve tissue using suspension culture techniques. These spheroids were characterized using flow cytometry, immunofluorescence, and reverse-transcription polymerase chain reaction. The conditioned media were evaluated in SH-SY5Y and RAW264.7 cell lines to assess their effects on neurogenesis and inflammation. To simulate TBI, we established a controlled cortical impact (CCI) model in rats. The animals were administered intrathecal injections of PNSC spheroids on three occasions, with each injection spaced at a 3-day interval. Recovery of sensory and motor function was assessed using the modified neurological severity score (mNSS) and rotarod tests, while histological (hematoxylin and eosin, Luxol fast blue staining) and T2-weighted magnetic resonance imaging analyses, alongside immunofluorescence, were conducted to evaluate the recovery of neural structures and pathophysiology. RESULTS: PNSC spheroids expressed high levels of Schwann cell markers and neurotrophic factors, such as neurotrophin-3 and Ephrin B3. Their conditioned medium was found to promote neurite outgrowth, reduce reactive oxygen species-mediated cell death and inflammation, and influence M1-M2 macrophage polarization. In the CCI rat model, rats receiving repeated triple intrathecal injections of PNSC spheroids showed significant improvements in sensory and motor function, with considerable neural tissue recovery in damaged areas. Notably, this treatment promoted nerve regeneration, axon regrowth, and remyelination. It also reduced glial scar formation and inflammation, while encouraging angiogenesis. CONCLUSION: Our findings suggest that repeated intrathecal injections of PNSC spheroids can significantly enhance neural recovery after TBI. This effect is mediated by the diverse neurotrophic factors secreted by PNSC spheroids. Thus, the strategy of combining therapeutic cell delivery with multiple intrathecal injections holds promise as a novel clinical treatment for TBI recovery.

Intravitreal Silicone Oil with a Silicone-free vs a Siliconized Syringe.

This randomized controlled trial compares incidence and quantity of presumed intravitreal silicone oil in diabetic patients receiving intravitreal injections using a silicone oil-free versus a siliconized syringe, highlighting the reduced contamination with silicone oil-free options.

[Mechanism of Xueshuantong Injection on bleomycin-induced pulmonary fibrosis in rats based on coagulation cascade pathway].

This study aims to investigate the mechanism of Xueshuantong Injection(XST) on pulmonary fibrosis induced by bleomycin(BLM) in rats based on the coagulation cascade pathway. Sixty SD rats were randomly divided into sham surgery group,model group, pirfenidone(PFD, 50 mg·kg~(-1)) group, and 27, 54, and 81 mg·kg~(-1) XST groups. The rat model of pulmonary fibrosis was established by intratracheal injection of BLM(5 mg·kg~(-1)). After 24 hours, the administration groups were given corresponding drugs, while the sham surgery group and model group were given equal volumes of saline. On the 28th day, samples were collected,and the imaging and collagen fiber changes in the lungs of rats were observed. Immunofluorescence(IF) method was used to detect the expression level of alpha-smooth muscle actin(α-SMA), collagen Ⅰ(Col-Ⅰ), E-cadherin(E-cad), and vimentin(Vim). Western blot was used to determine the protein expression of α-SMA, Col-Ⅰ, Vim, and E-cad. Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of prothrombin fragment(F1 + 2), thrombin-antithrombin complex(TAT), soluble fibrin monomer complex(SFMC), and rat fibrinogen degradation products(FDP) in rat lung tissue. Finally, the mRNA and protein levels of protease activated receptor 1(PAR-1) were detected by RT-qPCR, western blot, and IF. Compared with the model group, the scanning of the lungs of rats receiving XST treatment also exhibited patchy and non-homogeneous shadows, but these shadows were less dense than those in the model group. At the same time, there was a significant decrease in Col-Ⅰ fibers in the lungs of rats, and XST could inhibit epithelial-mesenchymal transition(EMT) and downregulate α-SMA and Col-Ⅰ protein expression. In the aspect of the coagulation system, administration of 81 mg·kg~(-1) XST significantly reduced the levels of SFMC and FDP. Meanwhile, 81 mg·kg~(-1) XST significantly downregulated the mRNA and protein levels of PAR-1. XST has an anti-pulmonary fibrosis effect in rats, and its mechanism may be related to the downregulation of PAR-1 to rebalance the coagulation cascade pathway.

[Prediction model of Reduning Injection content based on near-infrared and mid-infrared technology combined with spectral fusion].

In this paper, a method for rapidly determining the content of chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, gardeniside, and strychnoside in Reduning Injection(RI) was established based on near-infrared spectroscopy(NIRS), midinfrared spectroscopy(MIRS), and spectral fusion technology. Six pretreatment methods and five variable screening methods were investigated, and the best method was selected to establish a partial least square(PLS) model of two single spectra. At the same time,the NIRS and MIRS were fused with equal weights and characteristic bands, and the PLS model was established. The prediction effect of the four models on the quality control components was compared: NIRS>characteristic band fusion>MIRS>equal weight fusion. The relative standard error of prediction(RSEP) of the NIRS models on the five quality control components was less than 2. 5%, and the ratio of performance to deviation(RPD) was greater than 9. 5. The results show that the single spectrum model of NIRS is the best quantitative detection method, and the model of NIRS combined with the PLS algorithm can be used for the rapid detection of Reduning Injection.

[Comparison on tissue distribution of five components in Shuganning Injection and Scutellariae Radix extract by UPLC-MS/MS].

This study established an ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method to determine the content of five index components in rat tissues and organs after administration of Shuganning Injection or Scutellariae Radix extract. The dynamic changes and differences of the distribution of the five index components over time between the two groups were studied, and the effects of Scutellariae Radix alone or in combination with other medicines on the tissue distribution of the five components were explored. After Shuganning Injection or Scutellariae Radix extract was injected into the tail vein of rats, the heart, liver, spleen, lung, kidney, stomach, intestine, and brain tissue samples were collected at four time points of 0.17, 0.5, 1, and 2 h, respectively. UPLC-MS/MS was employed to measure the concentrations of the five index components(baicalin, baicalein, oroxylin A, oroxylin A-7-O-ß-D-glucuronide, and scutellarin) in the samples of the two groups. The results showed that the established method was simple, fast, and exclusively stable. After the administration of Shuganning Injection and Scutellariae Radix extract, the five index components presented wide distribution and had differences in vivo. The two groups showcased abundant distribution of baicalin, baicalein, and oroxylin A in the kidney and liver, oroxylin A-7-O-ß-D-glucuronide in the kidney and brain, and scutellarin in the kidney and heart. The content of baicalin in the heart, liver, kidney, and intestine, baicalein in the liver and kidney, and oroxylin A in the lung after administration of Shuganning Injection(Scutellariae Radix in combination with other medicines) was significantly higher than that after administration of Scutellariae Radix extract. The results of this study suggested that the five components of Shuganning Injection and Scutellariae Radix extract demonstrated wide distribution without accumulation in rats. The combination of Scutellariae Radix with other medicines can increase the distribution of active components in rats, which provided a basis for explaining the rationality of the compatibility of Shuganning Injection from in vivo processes.

[Mechanism of Huachansu Injection against colorectal cancer based on network pharmacology and cellular experimental].

This study aimed to elucidate the mechanism of Huachansu Injection(HCSI) against colorectal cancer(CRC) using network pharmacology, molecular docking technology, and cellular experimental. This research group initially used LC-MS/MS to detect the content of 16 bufadienolides in HCSI. Ten bufadienolide components were selected based on a content threshold of greater than 10 ng·mL~(-1). Their potential targets were further predicted using the SwissTargetPrediction database. CRC-related targets were obtained through GeneCards, OMIM, TTD, and PharmGKB databases. The intersection targets of HCSI in the treatment of CRC were obtained through Venny. The "active component-target-disease" network and target protein-protein interaction(PPI) network were constructed via Cytoscape software. Core targets were screened based on the degree values. Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed on these key targets. Molecular docking was conducted using AutoDock software on major bufadienolide active components and key targets. Different concentrations of HCSI, psi-bufarenogin(BUF), and bufotalin(BFT) were tested for their effects on cell viability, migration, and apoptosis rates in CRC HCT116 cells. Western blot was conducted to detect the expression of proteins related to the PI3K/Akt/mTOR signaling pathway in HCT116 cells. Eight main active components of HCSI, including arenobufagin, BUF, and BFT, as well as 20 key targets of HCSI in combating CRC, such as EGFR, IL6, and mTOR, were identified. Based on KEGG pathway enrichment and molecular docking results, the PI3K/Akt/mTOR signaling pathway was selected for further verification. Cellular experimental demonstrated that HCSI, BUF, and BFT significantly inhibited the proliferation and migration abilities of HCT116 cells, induced apoptosis in these cells, and downregulated the expression of PI3K/Akt/mTOR pathway-related proteins. This result suggests that HCSI, BUF, and BFT may exert their anti-CRC effects by regulating the PI3K/Akt/mTOR signaling pathway through targets such as mTOR and PIK3CA. This study provides theoretical evidence for exploring the active ingredients and mechanism of HCSI against CRC.

Monitoring of ketamine-based emerging contaminants in wastewater: a direct-injection method and fragmentation pathway study.

The ketamine (KET) and its analogs consumed by humans are becoming emerging contaminants (ECs), as they at present in surface waters after being carried through wastewater systems. Drugs in wastewater can be analyzed using the direct-injection method, a simple wastewater analysis (WWA) method that can provide objective, continuous and nearly to real-time findings. This article describes an ultra-high-pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification and confirmation of seven KET-based ECs in wastewater by direct injection. After optimization of the UPLC-MS/MS and sample pretreatment conditions, the method was validated and applied to samples (n = 157) collected from several wastewater treatment plants (WWTPs) in southern China in which KET had the highest detection rate. The established direct-injection method was not only simple to perform but also had better sensitivity, shorter detection times, and analyzed more KET-based ECs than currently published methods, meeting the requirements for the monitoring and high-throughput analysis of common KET-based ECs. We also analyzed the fragmentation pathway of KET-based ECs to obtain product ion information on other unknown substances. Additional studies are needed to establish a comprehensive direct-injection screening method of ECs in wastewater on model-based assessment.

Dataset of numerical study of the impact of two-step injection (direct and port) of hydrogen-enriched and natural gas mixtures on engine efficiency and exhaust emissions.

A study was conducted to examine the effects of two-step fuel injection on a modified four-cylinder engine that was converted from port to direct injection. The primary fuel source utilized was hydrogen-enriched compressed natural gas (HCNG), which replaced the conventional gasoline. In the initial phase of the procedure, compressed natural gas (CNG) was introduced into the intake manifold at a concentration of 10 % by mass, relative to the total fuel mixture. The remaining 90 % of the fuel consisted of HCNG, which was injected directly into the cylinders. The injection of compressed natural gas (CNG) commenced at 160° before top dead center (BTDC) with a 20° stroke duration. The HCNG fuel was injected in a two-step process. In the initial phase, HCNG was injected at 130° BTDC with a 50° stroke duration, with a stepwise increase from 0 % to 40 %. The study employed AVL software for the assessment of engine performance, efficiency, fuel consumption, and exhaust emissions. The data collected indicated that the injection of a 30 % HCNG blend resulted in an increase in brake power, brake thermal efficiency, and in-cylinder pressure (from 8 % to 13.64 %), as well as a reduction in specific fuel consumption (by 18 %). This improvement was attributed to an increase in flame propagation speed within the combustion chamber. Additionally, the percentage of excess hydrogen was found to decrease, resulting in a reduction of carbon monoxide and unburned hydrocarbons by up to 14 % due to complete combustion. However, NOx increased due to the rise in exhaust temperature.

Bridging the Gap Rather Than Filling the Entire Valley-Anatomic Insights When Treating the Medial Infraorbital Region.

BACKGROUND: The treatment of the medial infraorbital region also termed the tear trough has become increasingly popular by the use of soft tissue fillers in a minimally invasive approach using a cannula. METHODS: A total of 246 tear troughs were injected and investigated originating from 123 study participants. The clinical outcome was evaluated 6 months after the treatment by independent observers based on standardized frontal images and the procedure was documented by ultrasound imaging. RESULTS: On average, 0.26 (0.1) cc [range: 0.08-0.32] of soft tissue filler material was injected per tear trough. Tear trough depth was before the treatment rated as 2.12 (0.4), whereas after the treatment it was 1.15 (0.4) (p < 0.001). Hyperpigmentation score was 2.19 (0.4) before the treatment, whereas after the treatment it was 1.31 (0.5) (p < 0.001). Intraorbital fat pseudo-prolapse severity was rated before the treatment 1.88 (0.7), whereas it was rated after the treatment 1.14 (0.3) (p < 0.001). Wrinkle severity of the lower eyelid was rated before the treatment 1.51 (0.6), whereas it was rated after the treatment 1.12 (0.3) (p < 0.001). CONCLUSION: The results of this retrospectively investigated case series revealed that the conducted injection technique for treating the tear trough for medial infraorbital hollowing with a cannula provided statistically significant clinical improvement with a limited adverse events profile. The technique utilized an injection approach which was perpendicularly oriented to the longitudinal axis of the tear trough thereby "bridging the gap instead of filling the entire valley."

Injection therapy in professional footballers.

BACKGROUND: Injection therapy offers a minimally invasive approach for symptomatic relief that allows concurrent training, limiting time loss and providing a faster recovery. However, there is a lack of scientific evidence to support it, and there are controversies about its use. The present narrative review aims to present the available scientific literature on injection therapies in professional footballers (PF), highlighting the advantages and disadvantages of its use in the most common injuries. METHODS: The authors searched and reviewed contemporary literature on injection therapies in PF in electronic databases, summarizing them in a narrative review. RESULTS: Injection therapies such as hyaluronic acid and PRP have shown an adequate safety profile that allows their use. Current evidence suggests that hyaluronic acid injections are a valid option for managing symptomatic cartilage injuries. At the same time, PRP injections have failed to prove beneficial in treating muscle injuries and should be avoided until further evidence proves the opposite. Yet, PRP may have potential use in partial ACL injuries, anterior inferior tibiofibular ligament injuries (ankle syndesmosis), and fifth metatarsal fractures and needs further study. Due to the long-term health repercussions, other injection therapies should be preferred over corticosteroids in PF. CONCLUSIONS: There is a paucity of evidence on the use and benefits of injection therapies in PF despite its extensive use among physicians. Viscosupplementation may have a role in improving symptomatic cartilage injuries. In contrast, PRP injection therapy needs further high-quality clinical trials to assess its role in PF sports injuries.

Hypocrellin A against intrahepatic Cholangiocarcinoma via multi-target inhibition of the PI3K-AKT-mTOR, MAPK, and STAT3 signaling pathways.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive and highly lethal cancer with an increasing incidence worldwide that lacks effective treatment regimens. Hypocrellin A (HA), a natural small compound isolated from S. bambusicola, has multiple biomedical activities, including antitumor activity. PURPOSE: We intended to investigate the therapeutic effects of HA on ICC and its potential mechanisms. METHODS: RBE and HuccT1 cell lines were utilized for in vitro experiments. CCK8 assay, colony formation analysis, RTCA, and immunofluorescence staining of ki67 were employed to evaluate the suppression effects of HA on proliferation. The inhibitory effects of HA on cell migration and invasion were evaluate through transwell and wound healing assays, and Hoechst 33,258 staining was performed to evaluate apoptosis. Additionally, we performed transcriptome sequencing and molecular docking for targeting identification, and immunoblotting and immunofluorescence of key molecules for validation. Two in vivo models, HuccT1 xenografts, and the primary ICC model (KRAS/P19/SB) established via hydrodynamic tail-vein injection were implemented. Multiplex immunohistochemistry (mIHC) was used to illustrate the multi-target inhibitory effects of HA. RESULTS: The IC50 values of HA against RBE and HuccT1 cells were 4.612 µM and 10.01 µM for 24 h, as determined through the CCK8 assay. Our results confirmed that HA significantly repressed the proliferation, migration, invasion, and promoted the apoptosis of ICC cells at low concentrations. Moreover, HA exerted its anti-cancer effects through multi-target inhibition of the PI3K-AKT-mTOR, MAPK, and STAT3 signaling pathways. This inhibitory effect was rescued by Recilisib, an activator of the PI3K-AKT-mTOR pathway. Bioinformatics analysis of a multi-center RNA-Seq cohort (n = 90) demonstrated significant associations between these target pathways and the occurrence and poor prognosis of ICC. Animal studies suggested that HA strongly inhibited tumor growth in xenograft ICC models, and repressed the tumor number and size in the liver of primary ICC models by suppressing these three crucial pathways. CONCLUSION: HA, a novel natural small molecule, demonstrated promising therapeutic efficacy against ICC through its multi-target inhibitory effects on the PI3K-AKT-mTOR, MAPK, and STAT3 signaling pathways. Moreover, it exhibited notable therapeutic benefits in a primary ICC model (KRAS/P19/SB), positioning it as a novel therapeutic agent for ICC.

A Novel Crosslinked Hole Transport Layer with Enhanced Charge Injection Balance for Highly Efficient Inkjet-Printed Blue Quantum Dot-Based Light-Emitting Diodes.

In this work, an efficient and robust hole transport layer (HTL) based on blended poly((9,9-dioctylfluorenyl-2,7-diyl)-alt-(9-(2-ethylhexyl)-carbazole-3,6-diyl)) (PF8Cz) and crosslinkable 3,3'-(9,9-dimethyl-9H-fluorene-2,7-diyl)bis(9-(4-vinylphenyl)-9H-carbazole) (FLCZ-V) is introduced for high-performance and stable blue quantum dot-based light-emitting diodes (QLEDs), wherein FLCZ-V can in situ-crosslink to a continuous network polymer after thermal treatment and the linear polymer PF8CZ becomes intertwined and imprisoned. As a result, the blended HTL shows a high hole mobility (1.27 × 10-4 cm2 V-1 s-1) and gradient HOMO levels (-5.4 eV of PF8CZ and -5.7 eV of FLCZ-V) that can facilitate hole injecting so as to ameliorate the charge balance and, at the same time, achieve better electron-blocking capability that can effectively attenuate HTL decomposition. Meanwhile, the crosslinked blended HTL showed excellent solvent resistance and a high surface energy of 40.34 mN/m, which is favorable to enhance wettability for the deposition of a follow-up layer and attain better interfacial contact. Based on the blended HTL, blue QLEDs were fabricated by both spin-coating and inkjet printing. For the spin-coated blue QLED, a remarkable enhancement of external quantum efficiency (EQE) of 15.5% was achieved. Also, the EQE of the inkjet-printed blue QLED reached 9.2%, which is thus far the best result for the inkjet-printed blue QLED.

Easily injectable gelatin-nonanal hydrogel for endoscopic resectioning of gastrointestinal polyps.

The use of submucosal injection is crucial for satisfactory submucosal elevation in the early resection of flat polyps originating from the gastrointestinal tract (GIT). Injectable hydrogels derived from natural polypeptides are attractive candidates due to their excellent biocompatibility and easy gelation properties. However, most of the reported hydrogels are not the class of catheter delivery materials due to quick gelation, high inherent viscosity, and injection clogging. This study presents a novel injectable shear-thinning hydrogel platform of small molecules (nonanal) modified gelatin polymer, which offers a promising submucosal injection for effective removal of polyps from GIT. Physicochemical characterizations of hydrogel demonstrate the suitable features as an effective submucosal injection, including shear thinning property, self-assembly, methylene blue dye encapsulation, flow behavior, stability, syringeability (18 G, 21 G, and 24 G needles) and fibrous morphology. Ex vivo investigations of developed submucosal formulation on goat intestines demonstrate the enhanced visibility of cushions and the ability to produce stable, long-lasting cushions of about 8.07 mm up to ∼60 min of submucosal injection. The rapid blood clotting behavior of hydrogel was observed in about 120 s without compromising hemocompatibility with the hemolysis of about 3.77 % only. In vitro biocompatibility of the hydrogel was also verified using the HepG2 and nHDF cells. In vivo study depicts desirable biocompatibility, a non-toxic organ profile, and optimal cushion height in mice models. Studies established the foundation of novel submucosal fluid to improve the therapeutic outcomes of early resection for gastrointestinal polyps.

Sequential Injection Analysis Method for the Determination of Glutathione in Pharmaceuticals.

A sequential injection analysis method for the determination of glutathione (GSH) in pharmaceuticals has been developed. It is based on the reduction of the Cu(II)-neocuproine complex by GSH and the formation of an orange-yellow colored Cu(I)-neocuproine complex with maximum absorbance at 458 nm. Under optimal conditions the method is characterized by a linear calibration range of 6.0 × 10-7-8.0 × 10-5 mol L-1 (Amax = 3270 CGSH - 0.0010; R2 = 0.9983), limit of detection of 2.0 × 10-7 mol L-1, limit of quantification of 6.7 × 10-7 mol L-1, repeatability (expressed as relative standard deviation) of 3.8%, and sampling rate of 60 h-1. The newly developed method has been successfully applied to the determination of GSH in pharmaceutical samples with no statistically significant difference between the results obtained and those produced by the standard Pharmacopoeia method.