Vascular reconstruction provides short-term and long-term survival benefits for patients with hilar cholangiocarcinoma: A retrospective, multicenter study.

BACKGROUND: In patients with hilar cholangiocarcinoma (HCCA), radical resection can be achieved by resection and reconstruction of the vasculature. However, whether vascular reconstruction (VR) improves long-term and short-term prognosis has not been demonstrated comprehensively. METHODS: This was a retrospective multicenter study of patients who received surgery for HCCA with or without VR. Variables associated with overall survival (OS) and recurrence-free survival (RFS) were identified based on Cox regression. Kaplan-Meier curves were used to explore the impact of VR. Restricted mean survival time (RMST) was used for comparisons of short-term survival between the groups. Patients' intraoperative and postoperative characteristics were compared. RESULTS: Totally 447 patients were enrolled. We divided these patients into 3 groups: VR with radical resections (n = 84); non-VR radical resections (n = 309) and non-radical resection (we pooled VR-nonradical and non-VR nonradical together, n = 54). Cox regression revealed that carbohydrate antigen 242 (CA242), vascular invasion, lymph node metastasis and poor differentiation were independent risk factors for OS and RFS. There was no significant difference of RMST between the VR and non-VR radical groups within 12 months after surgery (10.18 vs. 10.76 mon, P = 0.179), although the 5-year OS (P < 0.001) and RFS (P < 0.001) were worse in the VR radical group. The incidences of most complications were not significantly different, but those of bile leakage (P < 0.001) and postoperative infection (P = 0.009) were higher in the VR radical group than in the non-VR radical group. Additionally, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) up to 7 days after surgery tended to decrease in all groups. There was no significant difference in the incidence of postoperative liver failure between the VR and non-VR radical groups. CONCLUSIONS: Radical resection can be achieved with VR to improve the survival rate without worsening short-term survival compared with resection with non-VR. After adequate assessment of the patient's general condition, VR can be considered in the resection.

Design and synthesis of 6-C-alkyl-DMDP type nanomolar inhibitors of ß-galactosidase and ß-glucosidase based on broussonetine S and related derivatives.

Broussonetine S (9), its C-1' and C-10' stereoisomers, and their corresponding enantiomers have been synthesized from enantiomeric arabinose-derived cyclic nitrones, with cross metathesis (CM), epoxidation and Keck asymmetric allylation as key steps. Glycosidase inhibition assays showed that broussonetine S (9) and its C-10' epimer (10'-epi-9) were nanomolar inhibitors of bovine liver ß-galactosidase and ß-glucosidase; while their C-1' stereoisomers were 10-fold less potent towards these enzymes. The glycosidase inhibition results and molecular docking calculations revealed the importance of the configurations of pyrrolidine core and C-1' hydroxyl for inhibition potency and spectra. Together with the docking calculations we previously reported for α-1-C-alkyl-DAB derivatives, we designed and synthesized a series of 6-C-alkyl-DMDP derivatives with very simple alkyl chains. The inhibition potency of these derivatives was enhanced by increasing the length of the side chain, and maintained at nanomolar scale inhibitions of bovine liver ß-glucosidase and ß-galactosidase after the alkyl groups are longer than eight or ten carbons for the (6R)-C-alkyl-DMDP derivatives and their 6S epimers, respectively. Molecular docking calculations indicated that each series of 6-C-alkyl-DMDP derivatives resides in the same active site of ß-glucosidase or ß-galactosidase with basically similar binding conformations, and their C-6 long alkyl chains extend outwards along the hydrophobic groove with similar orientations. The increasing inhibitions of ß-glucosidase and ß-galactosidase with the number of carbon atoms in the side chains may be explained by improved adaptability of longer alkyl chains in the hydrophobic grooves. In addition, the lower ß-glucosidase and ß-galactosidase inhibitions of (6S)-C-alkyl-DMDP derivatives than their C-6 R stereoisomers can be attributed to the misfolding of their alkyl chains and resulted decreased adaptability in the hydrophobic groove. The work reported herein is valuable for design and development of more potent and selective inhibitors of ß-galactosidase and ß-glucosidase, which have potential in treatment of lysosomal storage diseases. Furthermore, part of the 6-C-alkyl-DMDP derivatives and their enantiomers were also tested as potential anti-cancer agents; all the compounds tested were found with moderate cytotoxic effects on MKN45 cells, which would indicate potential applications of these iminosugars in development of novel anticancer agents.

Laparoscopic simultaneous anterograde inguinal and pelvic lymphadenectomy for penile cancer: two planses, three holes, and six steps.

Objective: To assess the feasibility, safety, and efficiency of simultaneous anterograde video laparoscopic inguinal and pelvic lymphadenectomy for penile cancer. Materials and methods: We reviewed retrospectively the records of 22 patients (44 lateral) who underwent inguinal lymph nodes dissection for penile cancer. The procedure was standardized as two planes, three holes, and six steps. Two Separate-planes: superior plane of eternal oblique aponeurosis/ / fascia lata; inferior plane of superficial camper fascia. Three holes: two artificial lateral boundary holes, the internal and external boundary holes, and the hole of oval fossa. Six steps: separate the first separate-plane; separate the second layer; separate two artificial lateral boundary holes; free great saphenous vein; separate the third hole and clean up the deep inguinal lymph nodes; pelvic lymphadenectomy. Results: A total of 22 cases were included and 9 patients underwent simultaneous pelvic lymphadenectomy. The average operation time on both sides was 7.52 ± 3.29 h, which was 0.5-1 h/side after skilled. The average amount of bleeding was 93.18 ± 50.84 ml. A total of 8 patients had postoperative complications, accounting for 36.36%, and no complications great than Clavien-Dindo class III occurred. Conclusion: This study demonstrated that the video laparoscopic simultaneous anterograde inguinal and pelvic lymphadenectomy is a feasible and safe technique. Indocyanine Green was helpful for lymph node identify.

A feasibility study on preoperative carbohydrate loading in older patients undergoing hip fracture surgery.

BACKGROUND: Preoperative carbohydrate loading in Enhanced Recovery After Surgery is an independent predictor of postoperative outcomes. By reducing the impact of surgical stress response, fasting-induced insulin resistance is modulated. As a clear fluid, consuming carbohydrate drink is safe up to 2 h preoperatively. Widely practiced in abdominal surgeries, its implementation in hip fracture surgeries is yet to be recognized. This study aimed to identify the feasibility of preoperative carbohydrate loading in hip fracture surgery and assess its clinical effects. METHODS: This was a randomized controlled, open labelled trial. Patients ≥ 65 years old without diabetes mellitus, has hip fracture were recruited in a tertiary hospital between November 2020 and May 2021. The intervention was carbohydrate loading versus standard preoperative fasting. RESULTS: Thirty-four ASA I-III patients (carbohydrate loading and control, n = 17 each), mean age 78 years (SEM ± 1.5), mean body mass index 23.7 (SEM ± 0.6 kg/m2) were recruited. Analysis for feasibility of carbohydrate loading (n = 17) demonstrated attrition rate of 29% (n = 5). Otherwise, all recruited patients were compliant (100% compliance) with no adverse events reported. There was no significant difference among groups in the postoperative nausea and vomiting, pain score, fatigue level, muscle strength, postoperative infection and length of hospital stay assessed at 24-48 h postoperatively. CONCLUSION: The implementation of preoperative carbohydrate loading was found to be feasible preoperatively in hip fracture surgeries but requires careful coordination among multidisciplinary teams. An adequately powered randomized controlled study is needed to examine the full benefits of preoperative carbohydrate loading in this group of patients. TRIAL REGISTRATION: This study was registered in ClinicalTrial.gov (ClinicalTrials.gov identifier: NCT04614181, date of registration: 03/11/2020).

Measurement of permanganate index in environmental water via indirect phase-conversion strategy.

In this work, we proposed an indirect phase-conversion strategy to construct a new approach for accurately and efficiently determining the permanganate index in water samples via headspace GC measurement. After the reducible substances in water reacted with excess potassium permanganate, the remaining potassium permanganate underwent a reaction with sodium oxalate under acidic conditions. The carbon dioxide generated from the gas-evolving reaction was then analyzed by headspace GC. Our findings showed that this new approach boasts high precision (relative standard deviation ≤ 2.18%) and accuracy for permanganate index analysis, thus validating the effectiveness of this new method in analyzing permanganate index. The introduction of the indirect phase-conversion strategy in this study is expected to set a precedent for further advancements in methodologies designed to indirectly evaluate substances capable of undergoing gas-producing reactions.

[Effects of plumbagin on proliferation and apoptosis of human hepatocellular carcinoma cells based on CKB/p53 signaling pathway].

To investigate the effects of plumbagin on the proliferation and apoptosis of human hepatoma Huh-7 cells and its mechanism based on the creatine kinase B(CKB)/p53 signaling pathway. Huh-7 cells were treated with plumbagin from 1 to 12 µmol·L~(-1) for cell counting kit-8(CCK-8) assay, and 1, 3, and 6 µmol·L~(-1) were determined as low, medium, and high concentrations of plumbagin for subsequent experiments. CKB gene was knocked out in Huh-7 cells by clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated proteins(Cas)-9 gene editing technology. CKB overexpression lentivirus was transfected into Huh-7 cells to up-regulate the expression of CKB. Cell proliferation and apoptosis were detected by plate cloning assay and flow cytometry. The mRNA expression of CKB was detected by quantitative real-time PCR(qRT-PCR). CKB, p53, mouse double minute 2 homolog(MDM2), B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), and caspase-3 protein were detected by Western blot(WB). The results showed that plumbagin significantly inhibited the proliferation of Huh-7 cells and induced cell apoptosis. Compared with the control group, the apoptosis level was significantly increased in the plumbagin group, while the apoptosis level was significantly decreased in the plumbagin combined with the apoptosis inhibitor group. Plumbagin significantly down-regulated the protein expression levels of CKB, Bcl-2, and MDM2 and up-regulated the protein expression levels of p53, Bax, and caspase-3. Knockdown of the CKB gene decreased the proliferative ability of Huh-7 cells, increased the apoptotic rate, decreased the expression levels of Bcl-2 and MDM2 proteins, and increased the expression levels of p53, Bax, and caspase-3 proteins. After up-regulation of CKB expression, the proliferation ability of Huh-7 cells was enhanced, and the protein expression levels of Bcl-2 and MDM2 were elevated. The protein expression levels of p53, Bax, and caspase-3 were decreased. In addition, plumbagin reversed the effect of overexpression of CKB on the proliferation and apoptosis of Huh-7 cells. In conclusion, plumbagin significantly inhibited the proliferative ability of Huh-7 cells, and the mechanism may be related to the inhibition of CKB expression, activation of the p53 signaling pathway, and regulation of the expression of mitochondrial-associated apoptotic proteins, ultimately inducing cell apoptosis.

Ab initio determination of melting and sound velocity of neon up to the deep interior of the Earth.

The thermophysical properties and elemental abundances of the noble gases in terrestrial materials can provide unique insights into the Earth's evolution and mantle dynamics. Here, we perform extensive ab initio molecular dynamics simulations to determine the melting temperature and sound velocity of neon up to 370 GPa and 7500 K to constrain its physical state and storage capacity, together with to reveal its implications for the deep interior of the Earth. It is found that solid neon can exist stably under the lower mantle and inner core conditions, and the abnormal melting of neon is not observed under the entire temperature (T) and pressure (P) region inside the Earth owing to its peculiar electronic structure, which is substantially distinct from other heavier noble gases. An inspection of the reduction for sound velocity along the Earth's geotherm evidences that neon can be used as a light element to account for the low-velocity anomaly and density deficit in the deep Earth. A comparison of the pair distribution functions and mean square displacements of MgSiO3-Ne and Fe-Ne alloys further reveals that MgSiO3 has a larger neon storage capacity than the liquid iron under the deep Earth condition, indicating that the lower mantle may be a natural deep noble gas storage reservoir. Our results provide valuable information for studying the fundamental behavior and phase transition of neon in a higher T-P regime, and further enhance our understanding for the interior structure and evolution processes inside the Earth.

Elimination of Intragrain Defect to Enhance the Performance of FAPbI3 Perovskite Solar Cells by Ionic Liquid.

Ionic liquids have been widely used to improve the efficiency and stability of perovskite solar cells (PSCs), and are generally believed to passivate defects on the grain boundaries of perovskites. However, few studies have focused on the relevant effects of ionic liquids on intragrain defects in perovskites which have been shown to be critical for the performance of PSCs. In this work, the effect of ionic liquid 1-hexyl-3-methylimidazolium iodide (HMII) on intragrain defects of formamidinium lead iodide (FAPbI3) perovskite is investigated. Abundant {111}c intragrain planar defects in pure FAPbI3 grains are found to be significantly reduced by the addition of the ionic liquid HMII, shown by using ultra-low-dose selected area electron diffraction. As a result, longer charge carrier lifetimes, higher photoluminescence quantum yield, better charge carrier transport properties, lower Urbach energy, and current-voltage hysteresis are achieved, and the champion power conversion efficiency of 24.09% is demonstrated. These observations suggest that ionic liquids significantly improve device performance resulting from the elimination of {111}c intragrain planar defects.

Establishment of a prognosis predictive model for liver cancer based on expression of genes involved in the ubiquitin-proteasome pathway.

BACKGROUND: The ubiquitin-proteasome pathway (UPP) has been proven to play important roles in cancer. AIM: To investigate the prognostic significance of genes involved in the UPP and develop a predictive model for liver cancer based on the expression of these genes. METHODS: In this study, UPP-related E1, E2, E3, deubiquitylating enzyme, and proteasome gene sets were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, aiming to screen the prognostic genes using univariate and multivariate regression analysis and develop a prognosis predictive model based on the Cancer Genome Atlas liver cancer cases. RESULTS: Five genes (including autophagy related 10, proteasome 20S subunit alpha 8, proteasome 20S subunit beta 2, ubiquitin specific peptidase 17 like family member 2, and ubiquitin specific peptidase 8) were proven significantly correlated with prognosis and used to develop a prognosis predictive model for liver cancer. Among training, validation, and Gene Expression Omnibus sets, the overall survival differed significantly between the high-risk and low-risk groups. The expression of the five genes was significantly associated with immunocyte infiltration, tumor stage, and postoperative recurrence. A total of 111 differentially expressed genes (DEGs) were identified between the high-risk and low-risk groups and they were enriched in 20 and 5 gene ontology and KEGG pathways. Cell division cycle 20, Kelch repeat and BTB domain containing 11, and DDB1 and CUL4 associated factor 4 like 2 were the DEGs in the E3 gene set that correlated with survival. CONCLUSION: We have constructed a prognosis predictive model in patients with liver cancer, which contains five genes that associate with immunocyte infiltration, tumor stage, and postoperative recurrence.

Establishing a new methodology for determining the water absorbability of cellulose-derived materials via a vapor-monitoring headspace strategy.

In this research, for the first time, we introduce a vapor-monitoring headspace strategy to establish a new methodology for determining the water absorbability of cellulose-derived materials. The method involves detecting the water in the gas phase from various cellulose-derived materials after achieving the equilibrium state. By utilizing the headspace technique to monitor the change in water vapor pressure from bound water to free water, a change point indicating the water absorbability can be identified through fitting procedures. The study showed that the newly-established method possesses high precision (relative standard deviation ≤2.92%) and accuracy (relative differences ≤5.74%) for water absorbability analysis. The present method emerges as a facile and reliable tool for measuring water absorbability, and the introduction of the vapor-monitoring headspace strategy is anticipated to inspire the development of a new type of analytical method.

Navigating Inconclusive Upper-Gastrointestinal Series in Infantile Bilious Vomiting: A Case Series on Intestinal Malrotation.

BACKGROUND Bilious vomiting in a child potentially portends the dire emergency of intestinal malrotation with volvulus, necessitating prompt surgical management, with differentials including small-bowel atresia, duodenal stenosis, annular pancreas, and intussusception. Although the upper-gastrointestinal series (UGI) is the diagnostic investigation of choice, up to 15% of the studies are inconclusive, thereby posing a diagnostic challenge. CASE REPORT We report a case series of 3 children referred for bilious vomiting, whose initial UGI was inconclusive and who were eventually confirmed to have intestinal malrotation at surgery. The first child was a female born at 37 weeks with antenatally diagnosed situs inversus and levocardia, who developed bilious vomiting on day 1 of life. The duodenojejunal flexure (DJ) could not be visualized on the UGI because of faint opacification on first pass of the contrast and subsequent overlap with the proximal jejunal loops. The second child was a male born at 36 weeks, presenting at age 4 months with bilious vomiting of 2 days duration. The third child was a female born at 29 weeks, presenting with bilious aspirates on day 3 of life. UGI for all 3 showed persistent hold-up of contrast at the proximal duodenum with no opacification of the distal duodenum or small bowel.Adjunctive techniques during the UGI and ultrasound examination helped achieve a preoperative diagnosis of malrotation in these children. CONCLUSIONS Application of diagnostic adjuncts to an inconclusive initial UGI may help elucidate a preoperative diagnosis of intestinal malrotation in infantile bilious vomiting.

Plumbagin Regulates Snail to Inhibit Hepatocellular Carcinoma Epithelial-Mesenchymal Transition in vivo and in vitro.

Background/Aims: Plumbagin (PL) has been shown to effe ctively inhibit autophagy, suppressing invasion and migration of hepatocellular carcinoma (HCC) cells. However, the specific mechanism remains unclear. This study aimed to investigate the effect of PL on tumor growth factor (TGF)-ß-induced epithelial-mesenchymal transition (EMT) in HCC. Methods: Huh-7 cells were cultured, and in vivo models of EMT and HCC-associated lung metastasis were developed through tail vein and in situ injections of tumor cells. In vivo imaging and hematoxylin and eosin staining were used to evaluate HCC modeling and lung metastasis. After PL intervention, the expression levels of Snail, vimentin, E-cadherin, and N-cadherin in the liver were evaluated through immunohistochemistry and Western blot. An in vitro TGF-ß-induced cell EMT model was used to detect Snail, vimentin, E-cadherin, and N-cadherin mRNA levels through a polymerase chain reaction. Their protein levels were detected by immunofluorescence staining and Western blot. Results: In vivo experiments demonstrated that PL significantly reduced the expression of Snail, vimentin, and N-cadherin, while increasing the expression of E-cadherin at the protein levels, effectively inhibiting HCC and lung metastasis. In vitro experiments confirmed that PL up-regulated epithelial cell markers, down-regulated mesenchymal cell markers, and inhibited EMT levels in HCC cells. Conclusion: PL inhibits Snail expression, up-regulates E-cadherin expression, and down-regulates N-cadherin and vimentin expression, preventing EMT in HCC cells and reducing lung metastasis.

Ascaris lumbricoides harbors a distinct gut microbiota profile from its human host: Preliminary insights.

In indigenous populations where soil-transmitted helminths (STH) infections are endemic, STH parasites (i.e., Ascaris lumbricoides, Trichuris trichiura, hookworms) often co-exist and co-evolve with the gut microbiota of their human hosts. The association between STH infections and the gut microbiota of the colonized human hosts has been established, but few studies explored the gut microbiota of the parasites. This preliminary study aimed to characterize the microbiota of the STH parasite for further understanding the STH parasite-host relationship. The gut microbial genomic DNA from four adult A. lumbricoides worms recovered from a six-year-old indigenous Negrito boy living in an STH-endemic village in Perak, Peninsular Malaysia was extracted and sequenced for the V3-V4 region of the 16S rRNA. The microbiota profiles of these worms were characterized and compared with the gut microbiota of their human host, including the profiles from four STH-positive and three STH-negative individuals from the same tribe and village. The gut microbial structure of A. lumbricoides was found to be differed significantly from their human host. The worms contained lower gut bacterial abundance and diversity than human. This difference was evident in the beta diversity analysis which showed a clear separation between the two sample types. While both Firmicutes (52.3%) and Bacteroidetes (36.6%) are the predominant phyla followed by Proteobacteria (7.2%) in the human gut, the microbiota of Ascaris gut is highly dominated by Firmicutes, constituting 84.2% relative abundance (mainly from the genus Clostridium), followed by Proteobacteria (11.1%), Tenericutes (1.8%) and Bacteroidetes (1.5%). The parasites were also found to alter the microbial structure of the human gut following infection based on the relatively higher bacterial abundance in STH-positive versus STH-negative participants. Further studies with a greater number of Ascaris adults and human hosts are needed to confirm the gut microbiota profiles.

Daily low-intensity pulsed ultrasound stimulation mitigates joint degradation and pain in a post-traumatic osteoarthritis rat model.

Objectives: The aim of this study was to investigate the effects of low-intensity pulsed ultrasound (LIPUS) in a post-traumatic osteoarthritis (OA) rat model and in vitro. Methods: Thirty-eight male, four-month-old Sprague Dawley rats were randomly assigned to Sham, Sham â€‹+ â€‹US, OA, and OA â€‹+ â€‹US. Sham surgery was performed to serve as a negative control, and anterior cruciate ligament transection was used to induce OA. Three days after the surgical procedures, Sham â€‹+ â€‹US and OA â€‹+ â€‹US animals received daily LIPUS treatment, while the rest of the groups received sham ultrasound (US) signals. Behavioral pain tests were performed at baseline and every week thereafter. After 31 days, the tissues were collected, and histological analyses were performed on knees and innervated dorsal root ganglia (DRG) neurons traced by retrograde labeling. Furthermore, to assess the activation of osteoclasts by LIPUS treatment, RAW264.7 â€‹cells were differentiated into osteoclasts and treated with LIPUS. Results: Joint degradation in cartilage and bone microarchitecture were mitigated in OA â€‹+ â€‹US compared to OA. OA â€‹+ â€‹US showed improvements in behavioral pain tests. A significant increase of large soma-sized DRG neurons was located in OA compared to Sham. In addition, a greater percentage of large soma-sized innervated neurons were calcitonin gene-related peptide-positive. Daily LIPUS treatment suppressed osteoclastogenesis in vitro, which was confirmed via histological analyses and mRNA expression. Finally, lower expression of netrin-1, a sensory innervation-related protein, was found in the LIPUS treated cells. Conclusion: Our findings demonstrate that early intervention using LIPUS treatment has protective effects from the progression of knee OA, including reduced tissue degradation, mitigated pain characteristics, improved subchondral bone microarchitecture, and less sensory innervation. Furthermore, daily LIPUS treatment has a suppressive effect on osteoclastogenesis, which may be linked to the suppression of sensory innervation in OA. The translational potential of this article: This study presents a new potential for early intervention in treating OA symptoms through the use of LIPUS, which involves the suppression of osteoclastogenesis and the alteration of DRG profiles. This intervention aims to delay joint degradation and reduce pain.

Protocol for preparation of highly durable superhydrophobic bulks with hierarchical porous structures.

Superhydrophobic surfaces face challenges in comprehensive durability when used in extreme outdoor environments. Here, we present a protocol for preparing nanocomposite bulks with hierarchical structures using the template technique. We describe steps for using hybrid nanoparticles of polytetrafluoroethylene and multi-walled carbon nanotube to fill inside and dip on the polyurethane (PU) foam. We then detail procedures for its removal by sintering treatment. The extra accretion layer on the PU foam surface was highlighted to construct hierarchical porous structures. For complete details on the use and execution of this protocol, please refer to Wu et al.1.

Comprehensive evaluation of rare case: From diagnosis to treatment of a sigmoid Schwannoma: A case report.

BACKGROUND: Schwannomas are uncommon tumors originating from Schwann cells, forming the neural sheath. They account for approximately 2%-6% of all mesenchymal tumors and are most commonly identified in peripheral nerve trunks, with rarity in the gastrointestinal tract. Among gastrointestinal locations, the stomach harbors the majority of nerve sheath tumors, while such occurrences in the sigmoid colon are exceptionally infrequent. CASE SUMMARY: This study presented a clinical case involving a 60-year-old female patient who, during colonoscopy, was diagnosed with a submucosal lesion that was later identified as a nerve sheath tumor. The patient underwent surgical resection, and the diagnosis was confirmed through immunohistochemistry. This study highlighted an exceptionally uncommon occurrence of a nerve sheath tumor in the sigmoid colon, which was effectively managed within our department. Additionally, a comprehensive review of relevant studies was conducted. CONCLUSION: The preoperative diagnosis of nerve sheath tumors poses challenges, as the definitive diagnosis still relies on pathology and immunohistochemistry. Although categorized as benign, these tumors have the potential to demonstrate malignant behavior. Consequently, the optimal treatment approach entails the complete surgical excision of the tumor, ensuring the absence of residual lesions at the margins.

Efficacy of bortezomib, cyclophosphamide, and dexamethasone for newly diagnosed POEMS syndrome patients.

Background: Due to the rarity of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, the best first-line treatment has not been established, although there are several options in guidelines. The preferred treatments vary according to the preference of the physician and anecdote. Objectives: First, to analyze the efficacy of a new treatment mode in POEMS syndrome that uses the four-cycle treatment as the induction regimen, followed by sequential transplantation as the consolidation regimen for transplantation-eligible patients, or received another two-cycle treatment for transplantation-ineligible patients. Second, to compare the efficacy and safety of regimens with a proteasome inhibitor (bortezomib-cyclophosphamide-dexamethasone, BCD) or without a proteasome inhibitor (cyclophosphamide-dexamethasone ± thalidomide, CD ± T). Design: We conducted a retrospective study using real-world data from Capital Medical University, Xuanwu Hospital. Methods: A total of 34 newly diagnosed POEMS syndrome patients met Dispenzieri's diagnostic criteria, and those who completed at least four cycles of treatment from July 2013 to March 2021 were included. Results: The overall vascular endothelial growth factor (VEGF) response rate of this new treatment mode was 100%. The cumulative VEGF complete remission (CRV) rate was 67.9%, and the cumulative complete hematological response (CRH) rate was 55.6%. During the median 49-month follow-up, the 5-year-overall survival (OS) rate was 90.7%, the 3-year-progression-free survival (PFS) rate was 78.4%, and the 5-year-PFS rate was 73.8%. The BCD regimen achieved a 75% CRV rate (median time from diagnosis to CRV = 130 days) and 66.7% CRH rate (median time from diagnosis to CRH = 218 days). In addition, the VEGF response was less than the partial remission (PRV) after four-cycle induction treatment, which, together with a decrease on the Overall Neurological Limitation Scale of less than three points 1 year after consolidation treatment, was an independent poor prognostic factor. Conclusion: Bortezomib was well-tolerated by patients with POEMS syndrome. Compared with CD ± T regimen, BCD as the induction regimen achieved better VEGF response and earlier hematological remission. Autologous stem cell transplantation used as consolidation therapy further improved the neurological and hematological remission rates, resulting in better OS and PFS.

Tracking of Stem Cells in Chronic Liver Diseases: Current Trends and Developments.

Stem cell therapy holds great promise for future clinical practice for treatment of advanced liver diseases. However, the fate of stem cells after transplantation, including the distribution, viability, and the cell clearance, has not been fully elucidated. Herein, recent advances regarding the imaging tools for stem cells tracking mainly in chronic liver diseases with the advantages and disadvantages of each approach have been described. Magnetic resonance imaging is a promising clinical imaging modality due to non-radioactivity, excellent penetrability, and high spatial resolution. Fluorescence imaging and radionuclide imaging demonstrate relatively increased sensitivity, with the latter excelling in real-time monitoring. Reporter genes specialize in long-term tracing. Nevertheless, the disadvantages of low sensitivity, radiation, exogenous gene risk are inevitably present in each of these means, respectively. In this review, we aim to comprehensively evaluate the current state of methods for tracking of stem cell, highlighting their strengths and weaknesses, and providing insights into their future potential. Multimodality imaging strategies may overcome the inherent limitations of single-modality imaging by combining the strengths of different imaging techniques to provide more comprehensive information in the clinical setting.

Sevoflurane anesthesia reduces the expression of inflammatory response genes and ß-site amyloid precursor protein-cleaving enzyme in hippocampi of diabetic mice.

Diabetes and inhaled anesthesia are associated with an increased likelihood of developing postoperative cognitive dysfunction in humans and animal models, but the mechanisms are unclear. This study aimed to investigate the effect and mechanism of sevoflurane anesthesia on cognitive function in diabetic (DM) mice. Spontaneously diabetic db/db and control db/m mice were subject to sevoflurane anesthesia or allowed to breathe air, respectively. The Morris water maze test as spatial learning and novel object recognition test as recognition memory were performed. The expression of inflammatory cytokines and neurotoxicity-related genes in the hippocampus of four groups was measured using real-time PCR. The expression level of neurotoxicity and neuroprotection-related proteins in DM mice hippocampus were estimated using Western blot assay. It is found that DM mice developed cognitive impairment; however, the cognitive impairment was not exacerbated in sevoflurane-exposed mice. Sevoflurane anesthesia led to a decrease in mRNA levels of inflammatory cytokines in DM mice hippocampi, including interleukin 17 (IL-17), C-C motif chemokine (CCL20), CCL7 as well as high mobility group box 1 and beta-site amyloid-ß cleaving enzyme 1; and no effect was observed on the expression of neurotoxicity genes, including amyloid precursor protein, choline O-acetyltransferase, tumor necrosis factor, alpha-induced protein 1, B-cell lymphoma 2 and estrogen receptor 2. In addition, we observed elevated phosphorylation of cAMP response element-binding protein in DM mice exposed to sevoflurane anesthesia. In conclusion, sevoflurane did not exacerbate DM-associated cognitive impairment.

ADP-dependent glucokinase controls metabolic fitness in prostate cancer progression.

BACKGROUND: Cell metabolism plays a pivotal role in tumor progression, and targeting cancer metabolism might effectively kill cancer cells. We aimed to investigate the role of hexokinases in prostate cancer (PCa) and identify a crucial target for PCa treatment. METHODS: The Cancer Genome Atlas (TCGA) database, online tools and clinical samples were used to assess the expression and prognostic role of ADP-dependent glucokinase (ADPGK) in PCa. The effect of ADPGK expression on PCa cell malignant phenotypes was validated in vitro and in vivo. Quantitative proteomics, metabolomics, and extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) tests were performed to evaluate the impact of ADPGK on PCa metabolism. The underlying mechanisms were explored through ADPGK overexpression and knockdown, co-immunoprecipitation (Co-IP), ECAR analysis and cell counting kit-8 (CCK-8) assays. RESULTS: ADPGK was the only glucokinase that was both upregulated and predicted worse overall survival (OS) in prostate adenocarcinoma (PRAD). Clinical sample analysis demonstrated that ADPGK was markedly upregulated in PCa tissues vs. non-PCa tissues. High ADPGK expression indicates worse survival outcomes, and ADPGK serves as an independent factor of biochemical recurrence. In vitro and in vivo experiments showed that ADPGK overexpression promoted PCa cell proliferation and migration, and ADPGK inhibition suppressed malignant phenotypes. Metabolomics, proteomics, and ECAR and OCR tests revealed that ADPGK significantly accelerated glycolysis in PCa. Mechanistically, ADPGK binds aldolase C (ALDOC) to promote glycolysis via AMP-activated protein kinase (AMPK) phosphorylation. ALDOC was positively correlated with ADPGK, and high ALDOC expression was associated with worse survival outcomes in PCa. CONCLUSIONS: In summary, ADPGK is a driving factor in PCa progression, and its high expression contributes to a poor prognosis in PCa patients. ADPGK accelerates PCa glycolysis and progression by activating ALDOC-AMPK signaling, suggesting that ADPGK might be an effective target and marker for PCa treatment and prognosis evaluation.