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Multilevel converters have gained significant popularity in medium-voltage and high-power applications due to their numerous advantages over traditional two-level converters. These advantages include reduced harmonic distortion, improved efficiency, and lower stress on power semiconductors. Selective harmonic elimination (SHE) is a modulation method that can be employed with multilevel converters to achieve high-quality output voltage waveforms. In this work, an extension of Broyden's method, known as the Quasi-Modified Newton Method, is implemented for selective harmonic elimination and accurate calculation of switching angles for a wide range of modulation indices. The proposed method is applied to cascaded H bridge inverters operating at levels 5, 7, and 9. The method offers simplicity, reduced computational burden, and faster convergence, making it easily implementable, reducing total harmonic distortion (THD), and reducing RMSE and MAD errors. The paper includes simulation and experimental results that validate the accuracy and effectiveness of the proposed approach., (© 2024. The Author(s).)

Background: Human herpesvirus 6B (HHV-6B) frequently reactivates following allogeneic stem cell transplant (alloHCT). Consensus guidelines note that haploidentical alloHCT may represent a high-risk population for which there is little evidence; this warrants further investigation., Methods: In this single-center retrospective study, we evaluated 188 consecutive adult patients receiving haploidentical alloHCT between 11/2014 and 11/2020 and compared outcomes between patients with HHV-6B reactivation receiving targeted antiviral therapy and those who were clinically observed., Results: Of the 58 included patients, 21 (36.2%) received antiviral therapy for HHV-6B reactivation with foscarnet (n = 19) or ganciclovir (n = 2). There were no differences in patient or disease characteristics between treated and observed patients. Treated patients were more likely to have high-level DNAemia (85.7% vs 40.5%; P < .001) and had higher peak viral quantitative measurements (median log 10 , 4.65 vs 3.84; P < .001). The median time to clearance from plasma (interquartile range) was 13 (7.25-20.00) days for all patients and was not significantly different between groups. There were no differences in episodes of encephalitis, grade III/IV acute graft-vs-host disease (GVHD), or time to neutrophil or platelet engraftment among treated vs observed patients. Day 100 nonrelapse mortality was not significantly different in the multivariate analysis; however, the presence of central nervous system symptoms was strongly associated with worse survival (hazard ratio, 4.11; 95% CI, 1.27-13.34; P = .018)., Conclusions: We did not observe a difference in clinical outcomes between the treated and observed groups of patients with HHV-6B reactivation following haploidentical alloHCT. With the rising use of haploidentical transplant and post-transplant cyclophosphamide GVHD prevention platforms, prospective studies are needed to further characterize the risk and outcomes associated with HHV-6B reactivation and therapy., Competing Interests: Potential conflicts of interest. G.H., Y.P., E.E., G.D., Y.P., O.K., A.B., A.J.F., F.K., A.S.M., L.O., L.P., M.N., F.P., and J.K. report no conflicts of interest. M.A. reports a consulting or advisory role with BMS and Janssen and speakers’ bureau membership with Janssen Oncology; H.E. reports a consulting or advisory role with Sanofi and Humanigen and research funding from BMS; D.K.H. reports a consulting or advisory role with BMS, Janssen, Pfizer, and Karyopharm and research funding from Janssen and Karyopharm; C.L.F. reports a consulting or advisory role with BMS, Seattle Genetics, Celgene, AbbVie, Sanofi, Incyte, Amgen, ONK Therapeutics, and Janssen and has received research funding from BMS, Janssen, and Roche/Genentech; M.D.J. reports a consultancy or advisory role for Kite/Gilead and Myeloid Therapeutics and received research funding from Kite/Gilead, Incyte, and Loxo@Lilly; F.L. reports a consulting or advisory role with Novartis, Celgene, Calibr, Alimera Sciences, Gerson Lehrman Group, EcoR1 Capital, Amgen, Bluebird Bio, BMS, Iovance Biotherapeutics, Legend Biotech, Cowen, Kite, a Gilead company, Umoja Biopharma, Takeda, Sana Biotechnology, Daiichi Sankyo/UCB Japan, Bristol Myers Squibb/Celgene, Janssen, A2 Biotherapeutics, Miltenyi Biotec, Caribou Biosciences, Takeda, and Umoja Biopharma and research funding from Kite, a Gilead company (Inst), Alimera Sciences (Inst), Novartis (Inst), Bluebird Bio (Inst), and Bristol Myers Squibb/Celgene (Inst); A.L. provides consultancy fees from, receives honoria from, and is a member of the scientific advisory board for Sanofi; H.D.L. has a membership on the board of directors of the advisory committee at BioLineRx; A.M. reports research funding from Novartis; T.N. reports research funding from Novartis and Karyopharm and is on the speakers’ bueau at Medexus Pharmaceuticals; J.P. reports a consulting and advisory board membership with Syndax, CTI Biopharma, Amgen, Regeneron, and Incyte and has received clinical trial funding from Novartis, Amgen, Takeda, Janssen, Johnson and Johnson, Pharmacyclics, AbbVie, CTI Biopharma, and BMS; O.C. reports a consulting or advisory role for Legend Biotech USA Inc. and Bristol Myers Squibb and being a member of the speakers’ bureau for Bristol Myers Squibb; N.B. provides consulting for and receives research funding from Orca Bio, CareDx Pharma, CRISPR, Sanofi, CTI BioPharma, Medexus Pharmaceuticals, and Magenta; R.F. receives research funding from Gilead., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Chimeric antigen receptor (CAR) T-cell therapy has transformed survival outcomes in patients with relapsed and refractory large B-cell lymphoma (LBCL), but it is associated with a variety of side effects. This study examined changes in patient-reported quality of life (QoL) and toxicities, as well as risk factors for worse QoL and toxicities, in the first year after treatment. Patients with LBCL completed questionnaires assessing QoL and toxicity severity before infusion, and 90, 180, and 360 days after infusion. Mixed models were used to examine changes in QoL and toxicities over time, and clinical moderators of change in QoL and toxicities. Patients reported improvements in physical functioning and fatigue in the year after treatment (P values <.01), but there were no changes in pain, anxiety, or depression over time. Patients with active disease at day 90 reported more physical dysfunction at all postinfusion timepoints (Ps ≤ .01) compared to patients who responded to treatment. Similarly, patients with active disease at day 90 reported worsening depression over time, such that at day 360, depressive symptoms were worse for patients with active disease than patients without active disease (P = .02). Patients treated with 4+ lines of prior therapy reported worsening pain and anxiety over time, such that at day 360, both pain and anxiety were significantly worse for patients previously treated with 4 of more lines of therapy than patients treated with fewer lines of therapy (Ps ≤ .01). Regarding toxicities, patients reported decreasing overall toxicity burden up to day 180, with subsequent worsening at day 360 (P = .02). Most patients reported at least one or two grade 2 toxicities at each timepoint. Patients demonstrated unchanging or improved QoL after treatment with CAR T-cell therapy, but active disease and greater prior lines of therapy were associated with worse QoL outcomes over time. Toxicity severity also improved during the first 6 months post-treatment, but worsened thereafter, particularly among patients with active disease after treatment., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The locked segment is critical for determining the stability of locked segment-type landslides. Research indicates that the volume expansion point marks the transition from the secondary creep stage to the tertiary creep stage in a landslide's evolution, and also separates the stable crack growth stage from the unstable crack growth stage in the locked segment. Identifying the volume expansion point is essential for early warning and predicting locked segment-type landslides. A series of instruments (resistance strain gauges, acoustic emission system, piezoelectric acceleration sensors, etc.) were used to conduct physical model tests of the landslide with retaining-wall-like locked segment under external load on the landslide's trailing edge. The evolution process of this landslide was analyzed through changes in slope shape and stress response characteristics. The experimental results reveal the failure mechanism of the landslide with retaining-wall-like locked segment: the upper part of the landslide thrusts and slides, the middle part squeezes and uplifts, the retaining-wall-like locked segment produces a locking effect, and compression-shear fracture of the retaining-wall-like locked segment leads to landslide failure. Based on the deformation and acoustic emission characteristics of the locked segment, a method for identifying the volume expansion point was established. This point was used as the onset of acceleration point in the inverse velocity method to predict the failure time of the locked segment-type landslides, incorporating the three-stage creep model and Fukumoto's theory., (© 2024. The Author(s).)

Nodal peripheral T cell lymphomas (PTCLs) are challenging subsets of non-Hodgkin lymphomas characterized by their heterogeneity and aggressive clinical behavior. Given the mixed outcomes reported in previous studies, the efficacy of autologous hematopoietic cell transplantation (auto-HCT) as a consolidation strategy following initial chemotherapy response remains uncertain. This study aims to evaluate the impact of upfront auto-HCT consolidation on overall survival (OS) and event-free survival (EFS) among patients with nodal PTCL who achieved a complete or partial response to initial chemotherapy. A retrospective cohort study was conducted at Moffitt Cancer Center, involving 123 patients with nodal PTCL treated between February 2005 and February 2021. Patients were stratified into 2 groups based on whether they received auto-HCT as part of their initial treatment strategy. Kaplan-Meier method and Cox proportional hazard models were used for statistical analysis to compare OS and EFS between groups. Patients undergoing auto-HCT after first response demonstrated significantly longer median OS (12.3 versus 4.3 yr; P = .035) and EFS (6.2 versus 2.2 yr; P = .003) compared to those who did not. Multivariate analyses indicated that auto-HCT at first response and younger age at diagnosis were favorable prognostic factors. The findings suggest that upfront auto-HCT consolidation can significantly improve long-term outcomes in patients with nodal PTCL, supporting the strategy of early auto-HCT consideration and referral following initial chemotherapy response. These results underscore the importance of integrating upfront auto-HCT into the treatment paradigm for nodal PTCL, emphasizing early referral to transplantation services to optimize patient outcomes., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

On 9 October 2022, the Large High Altitude Air Shower Observatory (LHAASO) reported the observation of the very early TeV afterglow of the brightest-of-all-time gamma-ray burst 221009A, recording the highest photon statistics in the TeV band ever obtained from a gamma-ray burst. We use this unique observation to place stringent constraints on the energy dependence of the speed of light in vacuum, a manifestation of Lorentz invariance violation (LIV) predicted by some quantum gravity (QG) theories. Our results show that the 95% confidence level lower limits on the QG energy scales are E&#95;{QG,1}>10 times the Planck energy E&#95;{Pl} for the linear LIV effect, and E&#95;{QG,2}>6×10^{-8}E&#95;{Pl} for the quadratic LIV effect. Our limits on the quadratic LIV case improve previous best bounds by factors of 5-7.

In this Letter we try to search for signals generated by ultraheavy dark matter at the Large High Altitude Air Shower Observatory (LHAASO) data. We look for possible γ rays by dark matter annihilation or decay from 16 dwarf spheroidal galaxies in the field of view of the LHAASO. Dwarf spheroidal galaxies are among the most promising targets for indirect detection of dark matter that have low fluxes of astrophysical γ-ray background while having large amount of dark matter. By analyzing more than 700 days of observational data at LHAASO, no significant dark matter signal from 1 TeV to 1 EeV is detected. Accordingly we derive the most stringent constraints on the ultraheavy dark matter annihilation cross section up to EeV. The constraints on the lifetime of dark matter in decay mode are also derived.

Background: The incidence of cholelithiasis has been on the rise in recent years, but the choice of procedure is controversial., Aim: To investigate the efficacy of laparoscopic cholecystectomy (LC) combined with endoscopic papillary balloon dilation (EPBD) in patients with gallbladder stones (GS) with common bile duct stones (CBDS)., Methods: The clinical data of 102 patients with GS combined with CBDS were selected for retrospective analysis and divided into either an LC + EPBD group ( n = 50) or an LC + endoscopic sphincterotomy (EST) group ( n = 52) according to surgical methods. Surgery-related indexes, postoperative recovery, postoperative complications, and expression levels of inflammatory response indexes were compared between the two groups., Results: Total surgical time, stone free rate, rate of conversion to laparotomy, and successful stone extraction rate did not differ significantly between the LC + EPBD group and LC + EST group. Intraoperative hemorrhage, time to ambulation, and length of hospitalization in the LC + EPBD group were lower than those of the LC + EST group ( P < 0.05). The rate of total complications of the two groups was 9.80% and 17.65%, respectively, and the difference was not statistically significant. No serious complications occurred in either group. At 48 h postoperatively, the expression levels of interleukin-6, tumor necrosis factor-α, high-sensitivity C-reactive protein, and procalcitonin were lower in the LC + EPBD group than in the LC + EST group ( P < 0.05). At 3 d postoperatively, the expression levels of aspartate transaminase, alanine transaminase, and total bilirubin were lower in the LC + EPBD group than in the LC + EST group ( P < 0.05)., Conclusion: LC combined with EPBD and LC combined with EST are both effective procedures for the treatment of GS with CBDS, in which LC combined with EPBD is beneficial to shorten the patient's hospitalization time, reduce the magnitude of elevated inflammatory response indexes, and promote postoperative recovery., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Two novel lanthanide mercury materials, [Gd(IA)3(H3O)2Hg3Br6]n·2nCl (1) and [La(IA)3(H3O)2Hg3Br6]n·2nCl (2) (IA = isonicotinic anion), have been prepared under solvothermal conditions and characterized by single-crystal X-ray diffraction techniques. They are isomorphic and characterized by a three-dimensional (3-D) framework structure. The lanthanide ions are bound by eight oxygen atoms to exhibit a square antiprismatic geometry. The solid-state photoluminescence experiment discovers that compound 1 shows a strong emission in the red region. Compound 1 possesses CIE (Commission Internationale de I'Éclairage) chromaticity coordinates of 0.7347 and 0.2653. Its CCT (correlated color temperature) is 6514 K. Compound 2 displays yellow photoluminescence and it has CIE chromaticity coordinates of 0.4411 and 0.5151. The CCT of compound 2 is 3633 K. Solid-state UV/Vis diffuse reflectance spectra revealed that their semiconductor band gaps are 2.16 eV and 2.85 eV, respectively.

The structural characteristics of fucoidans exhibit species and regional diversity. Previous studies have demonstrated that Laminaria japonica - and Ascophyllum nodosum -derived fucoidans have type I and type II fucosyl chains, respectively. These chemical differences may contribute to distinct hypolipidemic effects and mechanisms of action. Chemical analysis demonstrated that the percentage contents of sulfate, glucuronic acid, and galactose were higher in L. japonica -derived fucoidans than those of A. nodosum -derived fucoidans. In hyperlipidemic apolipoprotein E-deficient mice, both A. nodosum - and L. japonica -derived fucoidans significantly decreased the plasma and hepatic levels of total cholesterol and triglyceride, leading to the reduction of atherosclerotic plaques. Western blotting experiments demonstrated that these fucoidans significantly enhanced the expression and levels of scavenger receptor B type 1, cholesterol 7 alpha-hydroxylase A1, and peroxisome proliferator-activated receptor (PPAR)-α, contributing to circulating lipoprotein clearance and fatty acid degradation, respectively. Differentially, L. japonica -derived fucoidan significantly increased the LXR/ATP-binding cassette G8 signaling pathway in the small intestine, as revealed by real-time quantitative PCR, which may lead to further cholesterol and other lipid excretion. Collectively, these data are useful for understanding the hypolipidemic mechanisms of action of seaweed-derived fucoidans, and their potential application for the prevention and/or treatment of atherosclerotic cardiovascular diseases.

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15  PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.

This study proposes a novel honey bee dancing (HBD) maximum power point tracking (MPPT) algorithm inspired by the foraging behavior of honey bees. When a bee finds nectar, it returns to the honeycomb and dances to inform others about the location of the nectar. Other bees then fly towards the location and gather the nectar. The proposed HBD algorithm uses five bees searching for the nectar who communicate with each other about the location and the quantity of nectar by dancing. Finally, the five bees found the location of the most nectar which is represented by the maximum power point. The proposed HBD algorithm applies to uniform irradiance condition (UIC) and partial shaded condition (PSC). It is then compared with the PV panel output power and load relationship (OPLR) algorithm and perturb and observe (P&O) algorithm. Experimental verification has been performed under both the UIC and PSC. At the UIC's irradiance level of 200 W/m 2 , the PV module's output power for the proposed HBD algorithm, OPLR algorithm, and P&O algorithm are 120 W, 118 W, and 94.5 W, respectively, with efficiencies of 99 %, 97 %, and 78 %. Additionally, under the PSC with an irradiance level of 600 W/m 2 , the PV module's output power for the proposed HBD algorithm, OPLR algorithm, and P&O algorithm are 218 W, 189.2 W, and 74.8 W, respectively, with efficiencies of 99 %, 86 %, and 34 %, and convergence times of 4.7 ms, 6.5 ms, and 6 ms, respectively. It is evident from the results that the solar MPPT performance of the proposed HBD algorithm is better than the OPLR algorithm and P&O algorithm. This method ingeniously combines the foraging behavior of bees with solar power generation to produce the maximum natural power. This approach does not require the development of photovoltaic (PV) panel specification data, complex calculations, and additional temperature meters and heliographs. It is highly efficient and has significant economic benefits., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: With advancements in the development of endoscopic technologies, the endoscopic submucosal dissection (ESD) has been one of the gold-standard therapies for early gastric cancer., Aim: To investigate the efficacy and safety ESD in the treatment of early gastric cancer and precancerous lesions in the elderly patients., Methods: Seventy-eight elderly patients with early gastric cancer and precancerous lesions admitted to the Third Affiliated Hospital of Qiqihar Medical University were selected and classified into two groups according to the different surgical therapies they received between January 2021 and June 2022. Among them, 39 patients treated with ESD were included in an experimental group, and 39 patients treated with endoscopic mucosal resection (EMR) were included in a control group. We compared the basic intraoperative conditions, postoperative short-term recovery, long-term recovery effects and functional status of gastric mucosa between the two groups; the basic intraoperative conditions included lesion resection, intraoperative bleeding and operation time; the postoperative short-term recovery assessment indexes were length of hospital stay and incidence of surgical complications; and the long-term recovery assessment indexes were the recurrence rate at 1 year postoperatively and the survival situation at 1 year and 3 years postoperatively; and we compared the preoperative and predischarge serum pepsinogen I (PG I) and PG II levels and PG I/PG II ratio in the two groups before surgery and discharge., Results: The curative resection rate and the rate of en bloc resection were higher in the experimental group than in the control group. The intraoperative bleeding volume was higher in the experimental group than in the control group. The operation time was longer in the experimental group than that in the control group, and the rate for base residual focus was lower in the experimental group than that of the control group, and the differences were all statistically significant (all P < 0.05). The length of hospital stay was longer in the experimental group than in the control group, and the incidence of surgical complications, 1-year postoperative recurrence rate and 3-year postoperative survival rate were lower in the experimental group than in the control group, and the differences were statistically significant (all P < 0.05). However, the difference in the 1-year postoperative survival rate was not statistically significant between the two groups ( P > 0.05). Before discharge, PG I and PG I/PG II ratio were elevated in both groups compared with the preoperative period, and the above indexes were higher in the experimental group than those in the control group, and the differences were statistically significant (both P < 0.05). Moreover, before discharge, PG II level was lower in both groups compared with the preoperative period, and the level was lower in the experimental group than in the control group, and the differences were all statistically significant (all P < 0.05)., Conclusion: Compared with EMR, ESD surgery is more thorough. It reduces the rate of base residual focus, recurrence rate, surgical complications, and promotes the recovery of gastric cells and glandular function. It is safe and suitable for clinical application., Competing Interests: Conflict-of-interest statement: The authors report having no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

High-purity 1T'-WS 2 film has been experimentally synthesized [ Nature Materials , 20 , 1113-1120 (2021)] and theoretically predicted to be a two-dimensional (2D) superconducting material with Dirac cones [ arXiv :2301.11425]. In the present work, we further study the superconducting properties of monolayer 1T'-WS 2 by applying biaxial tensile strain. It is shown that the superconducting critical temperature T c firstly increases and then decreases with respect to tensile strains, with the highest superconducting critical temperature T c of 7.25 K under the biaxial tensile strain of 3%. In particular, we find that Dirac cones also exist in several tensile strained cases. Our studies show that monolayer 1T'-WS 2 may provide a good platform for understanding the superconductivity of 2D Dirac materials.

Background: Tongue diagnosis is a crucial traditional Chinese medicine (TCM) inspection method for TCM syndrome differentiation and treatment., Objective: The primary research focus was on tongue image characteristic parameters of patients with non-small cell lung cancer (NSCLC). Analysis of the tongue image parameters of various pathological stages of NSCLC provides technical support for establishing an integrated Chinese and Western auxiliary diagnosis and efficacy evaluation medicine system for lung cancer that integrates tongue image features., Methods: Tongue image characteristics of 309 patients with NSCLC and 206 controls were collected and analyzed clinically. The T-test or rank sum test and logistic regression analysis were applied to analyze the characteristics of tongue image indicators of different pathological stages of NSCLC., Results: There were differences in tongue image characteristics in the NSCLC group compared to the control group. The tongue quality and brightness of the tongue coating in the NSCLC group increased, the red component was reduced, the tongue coating thickened, and the yellow component increased compared to the healthy control group. A comparison of tongue image indexes of NSCLC in different pathological stages showed that stage IV had lower TB-b and higher TB-a than stage I. In addition, stage IV had lower TB-b than stage II + III, showing an increase in the blue and red components of the tongue in stage IV and the appearance of cyanotic tongue features., Conclusion: The tongue image characteristics of NSCLC patients differed from those of the control group. Tongue imaging indicators can reflect the characteristics of tongue images of patients with NSCLC. The tongue image characteristics of patients with stage IV lung cancer are bluish and purple compared with those with stage I, II, and III. It is suggested that the tongue's image characteristics can be used as a reference for the pathological classification of NSCLC and judgment of the disease process.

Background: Trastuzumab constitutes the fundamental component of initial therapy for patients with advanced human epidermal growth factor receptor 2 (HER-2)-positive gastric cancer (GC). However, the efficacy of this treatment is hindered by substantial challenges associated with both primary and acquired drug resistance. While S-phase kinase associated protein 2 (Skp2) overexpression has been implicated in the malignant progression of GC, its role in regulating trastuzumab resistance in this context remains uncertain. Despite the numerous studies investigating Skp2 inhibitors among small molecule compounds and natural products, there has been a lack of successful commercialization of drugs specifically targeting Skp2., Aim: To discover a Skp2 blocker among currently available medications and develop a therapeutic strategy for HER2-positive GC patients who have experienced progression following trastuzumab-based treatment., Methods: Skp2 exogenous overexpression plasmids and small interfering RNA vectors were utilized to investigate the correlation between Skp2 expression and trastuzumab resistance in GC cells. Q-PCR, western blot, and immunohistochemical analyses were conducted to evaluate the regulatory effect of thioridazine on Skp2 expression. A cell counting kit-8 assay, flow cytometry, a amplex red glucose/glucose oxidase assay kit, and a lactate assay kit were utilized to measure the proliferation, apoptosis, and glycolytic activity of GC cells in vitro. A xenograft model established with human GC in nude mice was used to assess thioridazine's effectiveness in vivo ., Results: The expression of Skp2 exhibited a negative correlation with the sensitivity of HER2-positive GC cells to trastuzumab. Thioridazine demonstrated the ability to directly bind to Skp2, resulting in a reduction in Skp2 expression at both the transcriptional and translational levels. Moreover, thioridazine effectively inhibited cell proliferation, exhibited antiapoptotic properties, and decreased the glucose uptake rate and lactate production by suppressing Skp2/protein kinase B/mammalian target of rapamycin/glucose transporter type 1 signaling pathways. The combination of thioridazine with either trastuzumab or lapatinib exhibited a more pronounced anticancer effect in vivo, surpassing the efficacy of either monotherapy., Conclusion: Thioridazine demonstrates promising outcomes in preclinical GC models and offers a novel therapeutic approach for addressing trastuzumab resistance, particularly when used in conjunction with lapatinib. This compound has potential benefits for patients with Skp2-proficient tumors., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Symptoms of hypocalcemia are reported in up to 50% of patients undergoing leukapheresis procedures. There is no set standard of practice for administering calcium supplementation in the prevention or treatment of hypocalcemia symptoms. The goal of this descriptive, retrospective study was to determine the prevalence of baseline hypocalcemia and symptomatic hypocalcemia during leukapheresis with acid citrate dextrose solution A and to identify patient characteristics associated with symptomatic hypocalcemia. Three percent of patients were found to have hypocalcemia before leukapheresis with 35% experiencing hypocalcemia symptoms during leukapheresis. Older age, higher albumin levels, and longer procedure time were associated with increased risk of hypocalcemia symptoms., (© 2023 Wiley Periodicals LLC.)

Microplastics (MPs) are abundant in aquaculture water, including in bioflocs aquaculture systems. Compared with other aquaculture systems, biofloc technology systems have the richest microbes and are beneficial to cultivated organisms. Therefore, this study provides a comprehensive assessment of the potential effects of MPs on aquaculture organisms in bioflocs systems. Here, Nile Tilapia (Oreochromis niloticus) were exposed to MPs (polystyrene; 32-40 μm diameter) with 0, 80 items/L (30 μg/L), and 800 items/L (300 μg/L) for 28 days in a bioflocs aquaculture system. The results showed that the MPs generally had no apparent effect on water quality, tilapia growth, or digestive enzyme activity. However, MPs accumulated the most in the liver (5.65 ± 0.74 μg/mg) and significantly increased the hepato-somatic index of tilapia and reduced the crude protein and lipid of tilapia muscle (p < 0.05). The levels of the antioxidant enzymes catalase and glutathione S-transferase increased significantly in response to MPs (p < 0.05). In contrast, MPs did not affect the content of glutathione, glutathione peroxidase, oxidized glutathione, and malondialdehyde, or the enzyme activity of Na + /K + -ATPase. Moreover, using an improved integrated biomarker response index, growth performance was found to be less responsive to MPs than to oxidative stress and digestive activity. Exposure to MPs did not significantly influence the microbial communities of the bioflocs and tilapia guts (p < 0.05). These results suggest that MPs barely affected tilapia in the bioflocs system. This study contributes to the evaluation of the ecological risk of MPs in aquaculture systems and a better understanding of the integrated response of cultivated vertebrates to MPs in biofloc technology systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°10  TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60  TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.

Cinnamigones A-C, three undescribed highly oxidized guaiane-type sesquiterpenes were isolated from the fruits of Cinnamomum migao. Cinnamigone A (1), structurally artemisinin-like, is a natural 1,2,4-trioxane caged endoperoxide with an unprecedented tetracyclic 6/6/7/5 ring system. Compounds 2-3 are classic guaiane sesquiterpene featuring different epoxy units. Guaiol (4) is considered to be the precursor of 1-3 in the biosynthesis pathway hypothesis. The planar structures and configurations of cinnamigones A-C were elucidated by spectral analysis, HRESIMS, X-ray crystallography and ECD calculations. Evaluation of the neuroprotective activity of 1-3 on N-methyl-ᴅaspartate (NMDA) toxicity was demonstrated that compounds 1-2 exhibited moderate neuroprotective activity against NMDA-induced neurotoxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Some gamma-ray bursts (GRBs) have a tera-electron volt (TeV) afterglow, but the early onset of this has not been observed. We report observations with the Large High Altitude Air Shower Observatory (LHAASO) of the bright GRB 221009A, which serendipitously occurred within the instrument's field of view. More than 64,000 photons >0.2 TeV were detected within the first 3000 seconds. The TeV flux began several minutes after the GRB trigger and then rose to a peak ~10 seconds later. This was followed by a decay phase, which became more rapid ~650 seconds after the peak. We interpret the emission using a model of a relativistic jet with half-opening angle of ~0.8°. This is consistent with the core of a structured jet and could explain the high isotropic energy of this GRB.

The Energy Recovery Ventilator (ERV) is proven efficient for residential ventilation applications. Yet, certain drawbacks, including a more confined space due to descended ceiling, a lengthy accompanying duct system, and over-ventilation issues that result in extensive energy consumption, need to be addressed. In this study, a novel Chain Recooling Energy Recovery Ventilator (CR-ERV) system is proposed to replace the typical ERV system design to solve the shortcomings above. By conducting an experiment on a three-bedroom condo in a hot and humid climate, it was found that compared to the natural ventilation strategy, the proposed system can help reduce the mean indoor carbon dioxide (CO 2 ) concentration from 976 to 677 ppm and PM 2.5 concentration from 6.4 to 4.1 μg/m 3 , representing a 29% and 34% reduction, respectively. From the regulatory perspective, only 64.4% of the natural-ventilated hours have a CO 2 concentration below the 1000 ppm limit per the local air quality Act. This fraction can be improved to 99% after adopting the proposed ventilation system. All these benefits come at the cost of a slight 2.3% increase in electricity consumption. In summary, the proposed system is proven efficient, and its implementation is fairly straightforward and economical; thus might be worth integrating into future residential building projects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The destruction of the locked-segment type landslide is often accompanied by the destruction of the locked segment with cumulative effects. Investigating the failure mode and instability mechanism of locked-segment type landslides is crucial. The study uses physical models to examine the evolution of locked-segment type landslides with retaining-walls. It utilizes a variety of instruments (tilt sensors, micro earth pressure sensors, pore water pressure sensors, strain gauges, and others) to conduct physical model tests of locked-segment type landslide with retaining-wall and to reveal the tilting deformation and evolution mechanism of retaining-wall locked landslide under the condition of rainfall. The results showed that the regularity of tilting rate, tilting acceleration, strain, and stress change in the retaining-wall locked segment is consistent with the landslide evolution process, indicating that tilting deformation can be used as the criterion of landslide instability and that the locked segment plays a vital role in controlling the landslide stability. The tertiary creep stages of tilting deformation are divided into initial, medium, and high tertiary creep stages using an improved angle tangent method. This establishes the failure criterion for locked-segment type landslides with tilting angles of 0.34°, 1.89°, and 4.38°. In addition, the tilting deformation curve of a locked-segment type landslide with a retaining-wall is utilized to predict the landslide instability by the reciprocal velocity method., (© 2023. The Author(s).)

Objective: To explore the difference in the protective effects of intraperitoneal injection of exogenous melatonin of daytime or nighttime on bone loss in ovariectomized (OVX) rats., Methods: After bilateral ovariectomy and sham surgery, 40 rats were randomly divided into four groups: sham operation group (Sham), ovariectomy (OVX), and daytime melatonin injection group (OVX + DMLT, 9:00, 30 mg/kg/d) and nighttime injection of melatonin (OVX + NMLT, 22:00, 30 mg/kg/d). After 12 weeks of treatment, the rats were sacrificed. The distal femur, blood and femoral marrow cavity contents were saved. The rest of the samples were tested by Micro-CT, histology, biomechanics and molecular biology. Blood was used for bone metabolism marker measurements. CCK-8, ROS, and Cell apoptosis are performed using MC3E3-T1 cells., Results: Compared with treatment at night, the bone mass of the OVX rats was significantly increased after the daytime administration. All microscopic parameters of trabecular bone increased, only Tb.Sp decreased. Histologically, the bone microarchitecture of the OVX + DMLT was also more dense than the bone microarchitecture of the OVX + LMLT. In the biomechanical experiment, the femur samples of the day treatment group were able to withstand greater loads and deformation. In molecular biology experiments, bone formation-related molecules increased, while bone resorption-related molecules decreased. After treatment with melatonin administration at night, the expression of MT-1β was significantly decreased. In cell experiments, the MC3E3-T1 cells treated with low-dose MLT had higher cell viability and greater efficiency in inhibiting ROS production than the MC3E3-T1 cells treated with high-dose MLT, which in turn more effectively inhibited apoptosis., Conclusion: Daytime administration of melatonin acquires better protective effects on bone loss than night in OVX rats., (© 2023. The Author(s).)

Radical gastrectomy for gastric cancer results in various post-operative complications, and the influencing factors are complicated. The diagnosis, treatment and prevention of common complications have been reported in many literatures. However, there are few reports on the prevention and treatment of rare complications. Rare complications after radical gastrectomy are often overlooked due to their low incidence. In addition, there are few guidelines and expert consensus regarding to the rare complications. Therefore, clinicians may lack experience in the diagnosis, treatment and prevention of rare complications after radical gastrectomy. Based on the literature review and the author's experience, this article systematically reviews seven rare complications after radical gastrectomy (duodenal stump fistula, pancreatic fistula, chyle leakage, esophagomediastinal fistula, internal hernia, gastroparesis, and intussusception). This article aims to provide a comprehensive reference for the diagnosis, treatment and prevention of rare complications after radical gastrectomy for gastric cancer patients.

Parkinson's disease (PD) is a prevalent type of neurodegenerative disease. There is mounting evidence that the gut microbiota is involved in the pathogenesis of PD. Sodium butyrate (NaB) can regulate gut microbiota and improve brain functioning in neurological disorders. Hence, we examined whether the neuroprotective function of NaB on PD was mediated by the modulation of gut microbial dysbiosis and revealed its possible mechanisms. Mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days to construct the PD model. NaB gavage was given 2 h after the daily MPTP injections for 21 days. NaB improved the motor functioning of PD mice, increased striatal neurotransmitter levels, and reduced the death of dopaminergic neurons. The 16S rRNA sequencing analysis revealed that NaB restored the gut microbial dysbiosis. NaB also attenuated the intestinal barrier's disruption and reduced serum, colon, and striatal pro-inflammatory cytokines, along with inhibiting the overactivation of glial cells, suggesting an inhibitory effect on inflammation from NaB throughout the gut-brain axis of the PD mice. Mechanistic studies revealed that NaB treatment suppressed the TLR4/MyD88/NF-kB pathway in the colon and striatum. In summary, NaB had a neuroprotective impact on the PD mice, likely linked to its regulation of gut microbiota to inhibit gut-brain axis inflammation.

Background: It is known that autophagy is essential for cell survival under stress conditions. Inorganic phosphate (Pi) is an essential nutrient for cell growth and Pi-limitation can trigger autophagy and lipid accumulation in oleaginous yeasts, yet protein (de)-phosphorylation and related signaling events in response to Pi limitation and the molecular basis linking Pi-limitation to autophagy and lipid accumulation remain elusive., Results: Here, we compared the proteome and phosphoproteome of Rhodotorula toruloides CGMCC 2.1389 under Pi-limitation and Pi-repletion. In total, proteome analysis identified 3,556 proteins and the phosphoproteome analysis identified 1,649 phosphoproteins contained 5,659 phosphosites including 4,499 pSer, 978 pThr, and 182 pTyr. We found Pi-starvation-induced autophagy was regulated by autophagy-related proteins, but not the PHO pathway. When ATG 9 was knocked down, the engineered strains produced significantly less lipids under Pi-limitation, suggesting that autophagy required Atg9 in R . toruloides and that was conducive to lipid accumulation., Conclusion: Our results provide new insights into autophagy regulation under Pi-limitation and lipid accumulation in oleaginous yeast, which should be valuable to guide further mechanistic study of oleaginicity and genetic engineering for advanced lipid producing cell factory., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Liu, Liu, Zhang, Jiao, Ye, Zhao and Zhang.)

Idecabtagene vicleucel (ide-cel) was FDA-approved in March 2021 for the treatment of relapsed/refractory multiple myeloma after 4 lines of therapy. On the KarMMa trial, grade ≥ 3 cytopenias and infections were common. We sought to characterize cytopenias and infections within 100 days after ide-cel in the standard-of-care (SOC) setting. This multi-center retrospective study included 52 patients who received SOC ide-cel; 47 reached day-90 follow-up. Data were censored at day 100. Grade ≥ 3 cytopenia was present among 65% of patients at day 30 and 40% of patients at day 90. Granulocyte colony stimulating factor (G-CSF) was administered to 88%, packed red blood cell transfusions to 63%, platelet transfusions to 42%, thrombopoietin (TPO) agonists to 21%, intravenous immunoglobulin to 13%, and CD34+ stem cell boosts to 8%. At day 100, 19% and 13% of patients had ongoing use of TPO agonists and G-CSF, respectively. Infections occurred in 54% of patients and were grade ≥ 3 in 23%. Earlier infections in the first 30 days were typically bacterial (68%) and severe (50%). Later infections between days 31 and 100 were 50% bacterial and 42% viral; only 13% were grade ≥ 3. On univariate analysis, high pre-CAR-T marrow myeloma burden (≥ 50%), circulating plasma cells at pre-lymphodepletion (LD), and grade ≥ 3 anemia at pre-LD were associated with grade ≥ 3 cytopenia at both days 30 and 90. Longer time from last bridging treatment to LD was the only significant risk factor for infection., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

The kilometer square array (KM2A) of the large high altitude air shower observatory (LHAASO) aims at surveying the northern γ-ray sky at energies above 10 TeV with unprecedented sensitivity. γ-ray observations have long been one of the most powerful tools for dark matter searches, as, e.g., high-energy γ rays could be produced by the decays of heavy dark matter particles. In this Letter, we present the first dark matter analysis with LHAASO-KM2A, using the first 340 days of data from 1/2-KM2A and 230 days of data from 3/4-KM2A. Several regions of interest are used to search for a signal and account for the residual cosmic-ray background after γ/hadron separation. We find no excess of dark matter signals, and thus place some of the strongest γ-ray constraints on the lifetime of heavy dark matter particles with mass between 10^{5} and 10^{9}  GeV. Our results with LHAASO are robust, and have important implications for dark matter interpretations of the diffuse astrophysical high-energy neutrino emission.

Theoretically and experimentally, MXenes consisting of Mo and C have aroused much interest due to superconductivity in their films and even monolayer forms. Here, based on first-principles calculations, we systematically calculate the electronic structure, phonon dispersion, and electron-phonon coupling (EPC) of monolayer Mo 2 C (both T- and H-phases), Mo 3 C 2 , and Mo 3 C 3 . The results show that H-Mo x C y ( x = 2 or 3, y = 1-3) always have lower total energies than their corresponding T phase and other configurations. All these two-dimensional (2D) molybdenum carbides are metals and some of them display weak phonon-mediated superconductivity at different superconducting transition temperatures ( T c ). The Mo 4d-orbitals play a critical role in their electronic properties and the Mo atomic vibrations play a dominant role in their low-frequency phonons, EPC, and superconductivity. By comparison, we find that increasing the Mo content can enhance the EPC and T c . Besides, we further explore the impact of strain engineering on their superconducting related physical quantities. With increasing biaxial stretching, the phonon dispersions are gradually softened to form some soft modes, which can trigger some peaks of α 2 F ( ω ) in the low-frequency region and evidently increase the EPC λ . The T c of H-Mo 2 C can be increased up to 11.79 K. Upon further biaxial stretching, charge density waves may appear in T-Mo 2 C, H-Mo 3 C 2 , and H-Mo 3 C 3 .

Background: Aloe polysaccharide (AP) is a type of an active macromolecule of Aloe vera, which contributes to its function. However, whether AP possesses anti-osteoporosis properties is unknown., Methods: Adipose-derived stromal cells were treated with different concentrations of AP. Early and late osteogenesis were, respectively, evaluated by ALP and Alizarin Red S staining. The effect of AP on the processes of adipogenesis inhibition in ADSCs was analyzed by oil red O staining. Western blot was used to assess the expression of osteogenic and adipogenic related factors. Then, Noggin was administered to further confirm the mechanism by which AP promotes the osteogenesis of ADSCs. Finally, 40 female SD rats were classified into a bilateral laparotomy group (Sham group) and three bilateral ovariectomy groups: OVX group, OVX + AP group, and OVX + AP + Noggin group. The bilateral rat femurs were collected to perform micro-CT scanning, HE, Masson trichrome, and Oil red O staining., Results: The results indicated that AP could increase ALP expression and calcium deposition. Through molecular mechanisms, AP promotes the protein expression of COL1A1, OPN, and ALP in ADSCs, but downregulates the expression of PPARγ. Also, AP directs ADSCs' fate by stimulating the BMP2/Smads signaling pathway. In vivo, the rat AP-treated had more trabecular bone than the OVX rat, indicating partial protection from cancellous bone loss after treatment with AP., Conclusion: Our results show that AP may promote osteogenesis of ADSCs through BMP-2/Smads signaling pathway and inhibits lipogenic differentiation. Thus, AP might be a promising alternative medicine to treat postmenopausal osteoporosis., (© 2022. The Author(s).)

Objectives: Flow cytometry (FC) is a critical diagnostic approach for guiding targeted chemotherapy and cellular immunotherapy for relapsed and refractory lymphoma patients. The aim of the study was to investigate the value of ultrasound-guided fine needle aspiration (FNA) to improve the quality of FC specimens in relapsed and refractory diffuse large B-cell lymphoma (R/R DLBCL)., Methods: Twenty patients with R/R DLBCL after standard treatment were included. The primary lesions of all cases were confirmed by pathology. FNA and core needle biopsy (CNB) were both used for ultrasound-guided puncture, the specimens obtained by FNA are directly examined by FC, and the specimens by CNB were subjected to FC after grinding. The accuracy of FC with the two methods were evaluated using histopathology as the gold standard., Results: Of the 20 R/R DLBCL cases, 19 were diagnosed as DLBCL pathologically and one was diagnosed as inflammatory granuloma. Among the specimens obtained by CNB, 14 cases examined by FC after grinding showed abnormal mature B cells, five cases were missed, all cases are not misdiagnosed. Among the specimens obtained by FNA, 18 cases showed FC-confirmed abnormal mature B cells, one case was missed, all cases are not misdiagnosed. The sensitivity, specificity, and accuracy of FC with CNB and FNA were 73.68 % (14/19) vs 94.73 % (18/19), 100 % (1/1) vs 100 % (1/1), and 75 % (15/20) vs 97.14 % (19/20), respectively. The sensitivity of the two puncture methods of FC of DLBCL was statistically different (p < 0.001)., Conclusion: Sampling with ultrasound-guided FNA is of great value to improve the quality of FC specimens. FNA can significantly improve the sensitivity and accuracy of FC diagnosis in R/R DLBCL., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Traumatic posterior atlantoaxial dislocation without fracture of the odontoid process is extremely rare. Only 24 cases have been documented since the first patient was reported by Haralson and Boyd in 1969. Although various treatment strategies are reported, no consensus has been yielded., Observations: A 58-year-old man experienced loss of consciousness and breathing difficulties after being struck by a car from behind. An immediate computed tomography scan showed subarachnoid hemorrhage, a posterior atlantoaxial dislocation without C1-2 fracture, and a right tibiofibular fracture. After the patient's respiration and hemodynamics were stabilized, closed reduction was attempted. However, this strategy failed due to unbearable neck pain and quadriplegia, resulting in surgical intervention with transoral odontoidectomy and posterior occipitocervical fusion. The patient developed postoperative central nervous system infection. After anti-infective and drainage treatment, the infection was controlled. At 1-year follow-up, the patient did not complain of special discomfort and was generally in good condition., Lessons: The authors report their experience with transoral odontoidectomy and concomitant posterior occipitocervical fusion in a case of posterior atlantoaxial dislocation without related fracture. Although these procedures are highly feasible and effective, particular attention should be paid to their complications, such as postoperative infection.

Objective: To summarize the experience in diagnosis and treatment of 45, X Turner syndrome (TS) with gonadal Y chromosome mosaicism and bilateral gonadoblastoma (Gb) secreting human chorionic gonadotrophin(HCG). Methods: A female patient aged 5 years and 3 months was admitted to the hospital with a complaint of "enlarged breasts for 27 months, and elevated blood β-HCG for 8 months". The clinical data were summarized, and related literature up to March 2022 with the key words"Turner syndrome" "Gonadoblastoma" "Y chromosome" "human chorionic gonadotropin" "precocious" in PubMed, CNKI and Wanfang databases were reviewed. Results: The girl went to the local hospital for 2-month breast development at age of 3 years, and was found with a heart murmur diagnosed with "pulmonary venous malformation and atrial septal defect (secondary foramen type)". Surgical correction was performed. She experienced the progressive breast development, rapid linear growth and markedly advanced skeletal age, which cannot be explained by partial activation in the hypothalamic-pituitary-gonadal axis determined at the age of 3 years and 7 months in local hospital. Then whole-exome sequencing revealed chromosome number abnormality 45, X, which was confirmed by Karyotyping. At the age of 4 years and 6 months, serum β-HCG was found to be elevated (24.9 U/L) with no lesion found at the local hospital. On physical examination, she was found with breast development, pubic hair development and clitoromegaly with elevated serum testosterone (1.96 μg/L) and β-HCG (32.3 U/L). Sex determining region Y(SRY) gene was negative in peripheral blood sample. Thoracic and abdominal CT, head and pelvic magnetic resonance imaging were normal. Exploratory laparotomy confirmed the presence of a left adnexal tumor and a right fibrous streak gonad. During surgery, simultaneous samples of bilateral gonadal and peripheral venous blood were obtained and serum β-HCG, estradiol and testosteron concentrations was higher to lower from left gonadal venous blood, right gonadal venous blood, to peripheral venous blood. Bilateral gonadectomy was performed. Histopathology revealed bilateral gonadoblastomas. SRY was positive in bilateral gonadal tissues. After surgery, serum E 2 , testerone and β-HCG returned to normal. So far 4 cases of HCG-secreting gonadoblastoma had been reported worldwide. The phenotypes of the 4 cases were all female, with virilization or amenorrhea, and the preoperative peripheral blood β-HCG concentrations were 74.4, 5.0, 40 456.0, and 42.4 U/L, respectively. Conclusions: There is a high risk of Gb in TS with Y chromosome components. Gb is infrequently presented with breast development, and Gb associated with HCG secretion is rare. Karyotyping should be performed in a phenotypic female with masculinization, and virilization in TS indicates the presence of Y chromosome material with concurrent androgen secreting tumors.

Intrauterine adhesion (IUA) is one of the most common diseases of the reproductive system in women. It is often accompanied by serious clinical problems that damage reproductive function, such as menstrual disorder, infertility, or recurrent abortion. The clinical effect of routine treatment is not ideal, and the postoperative recurrence rate is still very high. Therefore, exploring the pathological mechanism of IUA and finding new strategies for the effective prevention and treatment of IUA are needed. The main pathological mechanism of IUA is endometrial fibrosis and scar formation. Noncoding RNA (ncRNA) plays an important role in the fibrosis process, which is one of the latest research advances in the pathophysiology of IUA. Moreover, the exosomal miRNAs derived from mesenchymal stem cells can be used to improve IUA. This paper reviewed the role of ncRNAs in IUA pathogenesis, summarized the core pathways of endometrial fibrosis regulated by ncRNAs, and finally introduced the potential of ncRNAs as a therapeutic target., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu and Wang.)

Research has connected Parkinson's disease (PD) with impaired intestinal barrier. The activation of G-protein-coupled receptor 109A (GPR109A) protects the intestinal barrier by inhibiting the NF-κB signaling pathway. Sodium butyrate (NaB), which is a GPR109A ligand, may have anti-PD effects. The current study's objective is to demonstrate that NaB or monomethyl fumarate (MMF, an agonist of the GPR109A) can treat PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) via repairing the intestinal barrier. Male C57BL/6J mice were divided into four groups randomly: control, MPTP + vehicle, MPTP + NaB, and MPTP + MMF. Modeling mice received MPTP (20 mg/kg/day, i.p.) for a week, while control mice received sterile PBS. Then, four groups each received two weeks of sterile PBS (10 mL/kg/day, i.g.), sterile PBS (10 mL/kg/day, i.g.), NaB (600 mg/kg/day, i.g.), or MMF (100 mg/kg/day, i.g.). We assessed the expression of tight junction (TJ) proteins (occludin and claudin-1), GPR109A, and p65 in the colon, performed microscopic examination via HE staining, quantified markers of intestinal permeability and proinflammatory cytokines in serum, and evaluated motor symptoms and pathological changes in the substantia nigra (SN) or striatum. According to our results, MPTP-induced defected motor function, decreased dopamine and 5-hydroxytryptamine levels in the striatum, decreased tyrosine hydroxylase-positive neurons and increased activated microglia in the SN, and systemic inflammation were ameliorated by NaB or MMF treatment. Additionally, the ruined intestinal barrier was also rebuilt and NF-κB was suppressed after the treatment, with higher levels of TJ proteins, GPR109A, and decreased intestinal permeability. These results show that NaB or MMF can remedy motor symptoms and pathological alterations in PD mice by restoring the intestinal barrier with activated GPR109A. We demonstrate the potential for repairing the compromised intestinal barrier and activating GPR109A as promising treatments for PD.

Objective: To investigate the daily variation of LPR and the significance of 48-hour oropharyngeal pH monitoring in the diagnosis of LPRD. Methods: 72 subjects with suspected LPRD who were treated in our department from June 2018 to June 2021 were included. All patients were hospitalized to complete continuous 48-hour oropharyngeal Dx-pH monitoring. The consistency of Ryan index and W index and the correlation of various reflux parameters between the first and second 24-hour were compared. SPSS 24.0 was used for statistical analysis. Results: All 72 subjects successfully completed 48-hour oropharyngeal Dx-pH monitoring. Ryan index was positive in 11 cases (15.2%) in the first 24-hour, in 17 cases (23.6%) in the second 24-hour, in 5 cases (6.9%) both first and second, and in 23 cases (31.9%) in either 24-hour, Kappa =0.211 ( P =0.064), 18 cases (25%) had inconsistent results of the first 24-hour and the second 24-hour, and there was no significant difference in the positive rate between the first and second ( P =0.234). The number of positive cases in 48-hour monitoring increased by 109.1% compared with 24-hour monitoring.For W index, 49 cases (68.1%) were positive in the first 24-hourf 53 cases (73.6%) were positive in the second 24-hour, 42 cases (58.3%) were positive both first and second, and 58 cases (80.6%) were positive in either 24-hour, Kappa =0.477 ( P <0.001), 16 cases (22.2%) had inconsistent results of the first and second, and there was no significant difference in the positive rate between the first and second ( P =0.804). The number of positive cases in 48-hour monitoring increased by 18.4% compared with 24-hour monitoring. There was no significant difference in all the reflux parameters of first and second ( P >0.05). The correlation comparison showed that the correlation of various reflux parameters in the upright position was lower than that in the supine position. Conclusion: Laryngeal reflux has daily variability. Extending the monitoring time of Dx-pH to 48-hour can help reduce the missed diagnosis caused by daily variability; the use of W index can reduce the influence of daily variability on the diagnostic results of LPRD.

Objectives: The metagenomic next-generation sequencing (mNGS) test is useful for rapid and accurate detection and identification of pathogenic microorganisms. The aim of the present study was to investigate the factors associated with in-hospital mortality in pneumocystis pneumonia (PCP) patients with mNGS-assisted diagnosis., Methods: Our study enrolled 154 patients with mNGS-positive PCP from August 2018 to February 2022 at the First Affiliated Hospital of Zhengzhou University respectively. Patients were divided into the survivor group (n=98) and the death group (n=56) according to whether in-hospital death occurred. Baseline characteristics, patients' pre-hospital symptoms and patients' CT imaging performance during hospitalization were carefully compared between the two groups. Risk factors for the occurrence of in-hospital death were sought by selecting indicators that were significantly different between the two groups for modelling and performing multiple logistic regression analysis., Results: Compared with the in-hospital death patients, the survivors were younger and had higher levels of albumin (ALB) (age: 50.29 ± 14.63 years vs 59.39 ± 12.27 years, p<0.001; ALB: 32.24 ± 5.62 g/L vs 29.34 ± 5.42g/L, p=0.002; respectively), while the levels of lactate dehydrogenase (LDH) and C-reactive protein CRP were lower (LDH: 574.67 ± 421.24 U/L vs 960.80 ± 714.94 U/L, p=0.001; CRP: 54.97 ± 55.92 mg/L vs80.45 ± 73.26 mg/L, p= 0.018; respectively). Multiple logistic regression analysis revealed that age, the baseline LDH and CRP levels were all positively associated with high in-hospital mortality [age: OR(95%CI): 1.115 (1.062-1.172), p<0.001; LDH: OR(95%CI): 1.002 (1.001-1.003), p<0.001; CRP: OR(95%CI): 1.008 (1.000-1.017), p=0.045; respectively] while the platelet counts was negatively associated with it [OR(95%CI): 0.986 (0.979-0.992), p<0.001]., Conclusions: Old age, high baseline levels of LDH and CRP and low platelet counts were risk factors of the in-hospital mortality in mNGS positive PCP patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hou, Liu, Tan, Cao, Wang, Yao and Zhao.)

Background Aims: This white paper was developed to provide leukapheresis guidance for the collection of mononuclear cells from adult and pediatric patients who are destined for immune effector cell (IEC) therapies for commercial and research applications. Currently, there is considerable variability in leukapheresis processes and limited published information regarding best practices relevant to new cellular therapies, especially IECs. Herein the authors address critical leukapheresis questions in five domains to help guide consistent collection processes and ensure high-quality products. The first four domains are onboarding, pre-collection, collection and post-collection, with protocol feasibility, preparation, care and follow-up of the patient/donor at each step, respectively, and technical considerations during collection. The fifth domain of quality assurance focuses on ensuring product potency, purity, safety and auditing., Methods: The American Society for Apheresis (ASFA) Clinical Applications Committee (IEC Therapy Subcommittee) was charged by the society's board of directors with working collaboratively with other ASFA committees and organizations, including the Foundation for the Accreditation of Cellular Therapy, Association for the Advancement of Blood and Biotherapies, American Society for Transplantation and Cellular Therapy, National Marrow Donor Program and International Society for Cell & Gene Therapy, to develop guidelines regarding leukapheresis collection of cells destined for the manufacture of IEC therapies. After a review of the literature and discussion with members of the involved committees and various institutions, a draft guidance was created and circulated for comment and revision., Results: Critical aspects of apheresis that could affect the quality and quantity of the leukapheresis product were identified. These areas were then discussed and reviewed. After consensus, the best practice guidelines were proposed and accepted., Conclusions: In the current era of rapid growth of IEC therapies, it is important to address critical leukapheresis steps to provide high-quality products and more consistent practices and to eliminate redundant efforts., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Objective: To Summarize the safety, clinical outcome and technical evolution of laparoscopic gastric cancer surgery. Methods: A retrospective cohort study was carried out. Clinical data of 3012 patients who underwent laparoscopic radical gastrectomy for gastric cancer from January 2010 to March 2022 at Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University were retrospectively collected and analyzed. Case inclusion criteria were gastric malignancies confirmed by pathology, without distant metastasis by examination before operation and exploration during operation, patients undergoing laparoscopic radical gastrectomy, intact function of important organs and with complete data. Exclusion criteria were patients who underwent emergency gastric cancer resection due to gastric bleeding, perforation or obstruction, etc., tumor found to invade adjacent organs such as pancreas or transverse colon during the operation, conversion to open surgery during the operation, those who had other malignant tumors (except thyroid cancer) within 5 years, and those had severe cardiopulmonary, liver, or kidney insufficiency before surgery. Outcomes included: (1) baseline information of patients; (2) trend of the quantity of laparoscopic radical gastrectomy year by year; (3) evolution of the mode of digestive tract reconstruction; (4) periopertive outcome short-term complication was defined as complication occurring within 30 days after operation and classified accordiny to the clavien-Dindo criteria; and (5) 5-year overall survival. SPSS software was used for statistical analysis. Continuous variables that obeyed the normal distribution were expressed in the form of Mean±SD. Days of hospital stay that did not follow a normal distribution were expressed as median ( Q 1 , Q 3 ), and the Mann-Whiney U test was used for comparison. Discrete variables were expressed as cases (%), and chi-square test or rank sum test was used for comparison between groups. Linear regression analysis was used to analyze the relationship between the amount of surgery and the year of surgery. Kaplan-Meier method and log-rank test were used for survival analysis. Two-tailed P <0.05 was considered as statistically significant. Results: Among the 3012 cases, 2114 were male and 898 were female. The patients' average age at surgery was (61.1±10.7) years old. According to the number of cumulative cases, the patients were divided into three groups: early, intermediate and late, with 1004 patients in each group. The early group consisted of patients undergoing operation from January 2010 to October 2018, the intermediate group consisted of patients undergoing operation from October 2018 to January 2021, and the late group consisted of patients undergoing operation from January 2021 to March 2022. (1) General information: There were 691 (68.8%), 699 (69.6%) and 724 (72.1%) male patients in early, intermediate and late groups respectively; the average age increased from 56.6 years in 2010 to 62.8 years in March 2022. As for the tumor stage T1, T2, T3, T4, there were 49.0%, 14.4%, 23.9% and 12.6% in the early group; 47.5%, 12.9%, 26.9% and 12.6% in the intermediate group; 39.7%, 14.6%, 30.0%, and 15.6% in the late group, respectively. Patients with N0, N1, N2, N3a, N3b stage were 56.8%, 13.7%, 13.4%, 11.0%, and 5.0% in the early group; 55.7%, 12.9%, 12.8%, 11.6%, and 6.9% in the intermediate group; 51.0%, 16.1%, 12.8%, 12.5%, and 7.5% in the late group, respectively. (2) Year-by-year change in the number of gastric cancer operations: From 19 cases per year in 2010 to 786 per year in 2021, the annual number of gastric cancer operations was proportional to the year of operation (y=47.505x, R 2 =0.67). The proportion of patients with stage I disease showed a fluctuating downward trend over time, while the proportion of patients with stage III disease increased slightly, accounting for 34% until March 2022. (3) Evolution of digestive tract reconstruction methods: Except in 2010, the digestive tract reconstruction method of distal gastrectomy focused on Billroth-II+Braun anastomosis among patients undergoing laparoscopic gastric cancer surgery in other years, whose proportion had gradually increased from less than 20% in 2016 to about 70% after 2021; the gastrointestinal reconstruction methods after total gastrectomy had gradually increased in π anastomosis and overlap anastomosis since 2016, of which π anastomosis reached about 65% in 2019, and overlap anastomosis reached almost 30% in 2020; the anastomosis methods after proximal gastrectomy had been mainly double-channel anastomosis (54%) and esophagogastric anastomosis (30%) since 2016, and double-channel anastomosis accounted for up to 70% in 2019. (4) Operation time: The operation time of early, intermediate and late group was (193.3±49.8) min, (186.9±44.3) min and (206.7±51.4) min respectively. Intermediate group was significantly shorter than early group ( t =3.005, P =0.003), while late group was significantly longer than early group ( t =5.875, P <0.001) and intermediate group ( t =9.180, P <0.001). (5) Postoperative hospital stay: The median length of hospital stay for gastric cancer patients in early, intermediate and late groups was 9 (8, 11) d, 8 (7, 10) d, and 8 (7.5, 10) d respectively. The postoperative hospital stay of intermediate group and late group was significantly shorter than that of early group ( Z =-12.467, Z =-5.981, both P <0.001), but there was no significant difference between intermediate group and late group ( Z =0.415, P =0.678). (6) Postoperative complication: The morbidity of short-term complication in early, intermediate and late group was 20.4% (205/1004), 16.2% (163/1004), and 16.2% (162/1004) respectively, and above morbidity of intermediate group and late group was significantly lower than that of early group (χ 2 =5.869, P =0.015; χ 2 =6.165, P =0.013), while there was no significant difference between intermediate group and late group (χ 2 =0.004, P =0.952). The morbidity of short-term complication of grade IIIor higher was 8.0% (80/1004), 7.6% (76/1004), and 4.9% (49/1004) in early, intermediate and late group respectively, and above morbidity of late group was significantly lower than that of early and intermediate group (χ 2 =7.965, P =0.005; χ 2 =6.219, P =0.013), while there was no significant difference between intermediate group and early group (χ 2 =0.111, P =0.739). (7) Survival analysis: The follow-up deadline for survival data was December 31, 2021, and the median follow-up time was 29.5 months. The overall 5-year survival rate of all the patients was 74.7%. The 5-year survival rates of stage I, II and III patients were 92.0%, 77.2%, and 40.3% respectively and 5-year survival rates of patients with stage IA, IB, IIA, IIB, IIIA, IIIB and IIIC were 93.2%, 87.8%, 81.1%, 72.7%, 46.2%, 37.1%, and 34.0% respectively. Conclusions: The number of laparoscopic gastric cancer operation in our center is increasing year by year. With the maturity of laparoscopic technology, the morbidity of complication in laparoscopic gastric cancer surgery is decreasing.

Background: Anastomotic devices, including linear staplers (LSs) and circular staplers (CSs), have been widely used after laparoscopic gastric surgery. However, it is controversial whether linear stapling is superior to circular stapling for anastomosis. Thus, we conducted a meta-analysis to compare the aspects of postoperative complications, particularly anastomotic stricture and anastomotic leakage, on the use of the two techniques to assist clinical decision-making., Methods: We conducted a systematic search using Embase, PubMed, and Cochrane Library to evaluate studies that compared LSs and CSs after laparoscopic gastric surgery., Results: Pooled analysis suggested that patients who received LSs had fewer postoperative complications (P = 0.019), and anastomotic complications (P < 0.001), stricture (P = 0.001), and bleeding (P = 0.005). The subgroup analyses showed that LSs caused fewer anastomotic complications (P < 0.001), anastomotic strictures (P < 0.001), and postoperative hemorrhage (P = 0.007) in patients with gastric cancer than CS. In addition, LSs caused fewer incidences of overall morbidity (P = 0.042), anastomotic strictures (P = 0.023), postoperative hemorrhage (P < 0.001), wound infection (P < 0.001), and shorter length of hospital stay (P = 0.048) in patients with obesity. Furthermore, the subgroup analyses showed that the use of LS resulted in lower overall morbidity (P = 0.042), anastomotic stricture (P = 0.023), wound infection (P < 0.001), length of hospital stay (P = 0.048), and postoperative hemorrhage (P < 0.001) when applied in gastrojejunostomy, while LSs resulted in fewer anastomotic complications (P < 0.001), anastomotic stricture (P = 0.016) than CS when applied in esophagojejunostomy., Conclusion: Compared with CSs, LSs yielded a lower incidence of overall morbidity, anastomotic complications, anastomotic stricture, bleeding, and wound infection, indicating that linear stapling is safer and more efficient than circular stapling when performing anastomosis after laparoscopic gastric surgery.

Gaudichaudione H (GH), a caged polyprenylated xanthone from Garcinia plants, showed anti-cancer and anti-inflammatory effects in vitro. However, the in vivo toxicity of this compound has never been reported. The present study was aimed to address the toxic effects of Gaudichaudione H using zebrafish embryos and larvae as an in vivo test model. The zebrafish embryos were treated with GH having different concentrations (0, 0.28, 0.38 and 0.57 μg/mL). The results revealed that GH induces significant embryonic mortality, decreased heartbeat, cardiotoxicity, cardiovascular defects, increased apoptosis and decreased hemoglobinization in zebrafish embryos and larvae. According to transcriptome analysis, 1841 genes were significantly differentially expressed (1185 down-regulated and 656 up-regulated) after GH treatment. The main functions of these genes were related to iron metabolism pathways. The toxicity of GH on zebrafish embryonic development and cardiovascular may due to large amounts of downregulated genes involved in metabolic pathways and DEGs related to 'Iron ion binding' and 'Heme binding' functions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Chimeric antigen receptor T (CAR-T) cell successes have encouraged continued clinical study. Apheresis collection of starting material for CAR-T cell therapy product manufacturing is critical but described approaches suggest variability and clinical guidelines are currently lacking. The goal of this study was to gather and assess variability in apheresis collection descriptions in publicly available CAR T-cell therapy clinical trials., Study Design: We searched clinicaltrials.gov (a publicly available clinical trial database) for "chimeric antigen receptor T cells" on July 01, 2020 and studies accessed July 30, 2020-August 15, 2020. Data collected included date posted, study characteristics, apheresis mentions (number, location, and context), laboratory parameters and transfusion allowances. Apheresis context was analyzed using a qualitative inductive approach of grounded theory method with open coding. Text was classified into 37 context codes, grouped into 12 categories, and then consolidated into patient, procedure, product, and miscellaneous themes., Results: Apheresis was mentioned 1044 times in 322 (51.9%) of 621 total studies. Laboratory parameters mentioned included white blood cells (100 studies), absolute neutrophil count (220 studies), absolute lymphocyte count (102 studies), CD3 + cell (38 studies), hemoglobin (233 studies, 54 studies specified transfusion allowance), and platelet (269 studies, 48 studies specified transfusion allowance)., Conclusions: Apheresis collection of CAR-T cell products is not well-defined in clinical study descriptions and the context is inconsistent. Laboratory parameters useful for apheresis collection are variably present and do not consistently align with current practices. Further exploration, and clinical guideline development will encourage alignment of apheresis collections for CAR-T cell products., (© 2022 Wiley Periodicals LLC.)

Deuterium permeation through vanadium membranes in a wide range of pressures and the temperature range ~250-550 °C was experimentally investigated. Measurements on the same material were carried out in three laboratories with different features for an extended characterization and for cross-check validation. A unified equation for deuterium permeability in pure vanadium (99%) was provided as Φ=1.27×10-4·e-8667/T mol m -1 s -1 Pa -0.5 , which represents a significant progress for the characterization of the transport properties in this material, given the spread of data, which can currently be found in the literature. Adsorption and recombination rate constants were also measured for hydrogen and deuterium at low pressure for the same range of temperatures. Finally, the influence of the surface roughness was examined by measuring samples with different surface finish.

Instability failure in rock mass engineering is closely related to expansion of joint fissures. In this study, uniaxial compression tests and acoustic emission (AE) measurements were carried out simultaneously on specimens of soft rock-like material with different fracture angles and connectivity values to better understand their influence on the deformation and failure of the material. The stress-strain curve and AE signal of fractured soft rock-like material are similar to those of intact soft rock-like; specifically, they exhibit a compaction, elastic deformation, stable fracture development, and unstable fracture development. The main differences between fractured and intact material occur during post-peak failure stage. Under the combined influence of fracture angle and connectivity, the uniaxial compressive strength of fractured soft rock-like material ([Formula: see text]) is lower than that of the intact soft rock-like material (f cu ), and can be described by the relationship [Formula: see text], where [Formula: see text] is the strength reduction coefficient, fitted as [Formula: see text]. In this equation, x is the fracture angle ([Formula: see text]) and y is the fracture connectivity (%). Under uniaxial compression, the main types of secondary cracks were wing cracks and secondary coplanar cracks. The specimen with a fracture angle of 30° mainly underwent tensile failure under loading, whereas those with fracture angles of 45° and 60°mainly experienced shear failure under high-connectivity conditions (45%)., (© 2022. The Author(s).)