Psychometric validation of the Chinese version of the dry eye-related quality-of-life score questionnaire.

AIM: To psychometrically validate the Chinese version of the dry eye-related quality-of-life score questionnaire (DEQS-CHN) among Chinese patients with dry eye. METHODS: This study involved 231 participants, including 191 with dry eye disease (DED) comprising the dry eye disease group, and 40 healthy participants forming the control group. Participants were required to complete the DEQS-CHN, and Chinese dry eye questionnaire and undergo clinical tests including the fluorescein breakup time (FBUT), corneal fluorescein staining (CFS), and Schirmer I test. To assess the internal consistency and retest reliability, Cronbach's α and the intraclass correlation coefficient (ICC) were employed. Content validity was assessed by item-level content validity index (ICV) and an average scale-level content validity index (S-CVI/Ave). Construct validity was assessed by confirmatory factor analysis. The concurrent validity was assessed by calculating correlations between DEQS-CHN and Chinese dry eye questionnaire. Discriminative validity was evaluated through non-parametric tests, with receiver operating characteristic (ROC) curve serving as conclusive indicators of the questionnaire's distinguishing capability. RESULTS: The Cronbach's α coefficients for frequency and degree of ocular symptoms, impact on daily life, and summary score were 0.736, 0.704, 0.811, 0.818, 0.861, and 0.860, respectively, and the ICC were 0.611, 0.677, 0.715, 0.769, 0.711, and 0.779, respectively. All I-CVI scores ranged from 0.833 to 1.000, with an S-CVI/Ave of 0.956. Confirmatory factor analysis results exhibited a well-fitting model consistent with the original questionnaire [χ 2/df=2.653, incremental fit index (IFI)=0.924, comparative fit index (CFI)=0.924, Tucker-Lewis index (TLI)=0.909, and root mean square error of approximation (RMSEA)=0.065]. There was a moderate positive correlation between the DEQS-CHN and the Chinese dry eye questionnaire (r 2=0.588). The dry eye group demonstrated significantly higher scores compared to the control group, and the area under the curve (AUC) value was 0.8092. CONCLUSION: The DEQS-CHN has been demonstrated as a valid and reliable instrument for assessing the impact of dry eye disease on the quality of life among Chinese individuals with DED.

Enhanced water stability of MOFs via multiple hydrogen bonds and their application in water harvesting.

A mechanism based on multiple hydrogen bonds was proposed to describe the great water stability of some hydrated Cu paddle-wheel-based MOFs, which was demonstrated through density functional theory (DFT) calculations and single-crystal X-ray diffraction (SCXRD) of water-loaded MOFs. This mechanism endowed Cu-TDPAT with exceptional water stability and outstanding atmospheric water harvesting capability.

Talin2 binds to non-muscle myosin IIa and regulates cell attachment and fibronectin secretion.

Talin2 is localized to large focal adhesions and is indispensable for traction force generation, invadopodium formation, cell invasion as well as metastasis. Talin2 has a higher affinity toward ß-integrin tails than talin1. Moreover, disruption of the talin2-ß-integrin interaction inhibits traction force generation, invadopodium formation and cell invasion, indicating that a strong talin2-ß-integrin interaction is required for talin2 to fulfill these functions. Nevertheless, the role of talin2 in mediation of these processes remains unknown. Here we show that talin2 binds to the N-terminus of non-muscle myosin IIA (NMIIA) through its F3 subdomain. Moreover, talin2 co-localizes with NMIIA at cell edges as well as at some cytoplasmic spots. Talin2 also co-localizes with cortactin, an invadopodium marker. Furthermore, overexpression of NMIIA promoted the talin2 head binding to the ß1-integrin tail, whereas knockdown of NMIIA reduced fibronectin and matrix metalloproteinase secretion as well as inhibited cell attachment on fibronectin-coated substrates. These results suggest that talin2 binds to NMIIA to control the secretion of extracellular matrix proteins and this interaction modulates cell adhesion.

Chronic prostatitis/chronic pelvic pain syndrome induces metabolomic changes in expressed prostatic secretions and plasma.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.

Uveal melanoma distant metastasis prediction system: A retrospective observational study based on machine learning.

Uveal melanoma (UM) patients face a significant risk of distant metastasis, closely tied to a poor prognosis. Despite this, there is a dearth of research utilizing big data to predict UM distant metastasis. This study leveraged machine learning methods on the Surveillance, Epidemiology, and End Results (SEER) database to forecast the risk probability of distant metastasis. Therefore, the information on UM patients from the SEER database (2000-2020) was split into a 7:3 ratio training set and an internal test set based on distant metastasis presence. Univariate and multivariate logistic regression analyses assessed distant metastasis risk factors. Six machine learning methods constructed a predictive model post-feature variable selection. The model evaluation identified the multilayer perceptron (MLP) as optimal. Shapley additive explanations (SHAP) interpreted the chosen model. A web-based calculator personalized risk probabilities for UM patients. The results show that nine feature variables contributed to the machine learning model. The MLP model demonstrated superior predictive accuracy (Precision = 0.788; ROC AUC = 0.876; PR AUC = 0.788). Grade recode, age, primary site, time from diagnosis to treatment initiation, and total number of malignant tumors were identified as distant metastasis risk factors. Diagnostic method, laterality, rural-urban continuum code, and radiation recode emerged as protective factors. The developed web calculator utilizes the MLP model for personalized risk assessments. In conclusion, the MLP machine learning model emerges as the optimal tool for predicting distant metastasis in UM patients. This model facilitates personalized risk assessments, empowering early and tailored treatment strategies.

Total synthesis of the hexasaccharide arabinan domain of mycobacterial arabinogalactan.

The hexasaccharide arabinan domain of Mycobacterial Arabinogalactan was provided with the versatile methodology toward ß-selective arabinofuranosylation directed by B(C6F5)3, demonstrating the effectiveness of the ß-arabinofuranosylation strategy. Derivatization of the amino moiety at the reducing end are essential prerequisites for elucidating the biosynthetic pathway and conjugating of this compound to a protein carrier for vaccine generation.

B(C6F5)3-Catalyzed Stereoselective 1,2-cis Arabinofuranosylation with a Conformationally Constrained Donor.

Compared with stereoselective glycosylation methods mainly addressed on the preparation of pyranose glycosides, the furanosylation has been more limited, especially for the 1,2-cis arabinofuranosylation. Herein, we report a novel stereoselective 1,2-cis-arabinofuranosylation strategy using a conformationally restricted 3,5-O-xylylene-protected arabinofuranosyl donor on activation with B(C6F5)3 for desired targets in moderate to excellent yields and ß-stereoselectivity. The effectiveness of the 1,2-cis-arabinofuranosylation strategy was demonstrated successfully with various acceptors, including carbohydrate alcohols.

Hyperactivation of succinate dehydrogenase promotes pyroptosis of macrophage via ROS-induced GSDMD oligomerization in acute liver failure.

Acute liver failure (ALF) is a life-threatening disease with high mortality. Given excessive inflammation is one of the major pathogenesis of ALF, candidates targeting inflammation could be beneficial in the condition. Now the effect of hyperactivated succinate dehydrogenase (SDH) on promoting inflammation in lipopolysaccharide (LPS)-treated macrophages has been studied. However, its role and mechanism in ALF is not well understood. Here intraperitoneal injection of D-galactosamine and LPS was conducted in male C57BL/6 J mice to induce the ALF model. Dimethyl malonate (DMM), which inhibited SDH activity, was injected intraperitoneally 30 min before ALF induction. Macrophage pyroptosis was induced by LPS plus adenosine triphosphate (ATP). Pyroptosis-related molecules and proteins including GSDMD oligomer were examined by ELISA and western blot techniques, respectively. ROS production was assessed by fluorescence staining. The study demonstrated SDH activity was increased in liver macrophages from ALF mice. Importantly, DMM administration inhibited ROS, IL-1ß, and pyroptosis-associated proteins levels (NLRP3, cleaved caspase-1, GSDMD-N, and GSDMD oligomers) both in the ALF model and in macrophages stimulated with LPS plus ATP. In vitro, ROS promoted pyroptosis by facilitating GSDMD oligomerization. Additionally, when ROS levels were increased through the addition of H2O2 to the DMM group, the levels of GSDMD oligomers were reverted. In conclusion, SDH hyperactivation promotes macrophage pyroptosis by ROS-mediated GSDMD oligomerization, suggesting that targeting this pathway holds promise as a strategy for treating ALF and other inflammatory diseases.

High-Performance Monolithic 3D Integrated Complementary Inverters Based on Monolayer n-MoS2 and p-WSe2.

Herein, the structure of integrated M3D inverters are successfully demonstrated where a chemical vapor deposition (CVD) synthesized monolayer WSe2 p-type nanosheet FET is vertically integrated on top of CVD synthesized monolayer MoS2 n-type film FET arrays (2.5 × 2.5 cm) by semiconductor industry techniques, such as transfer, e-beam evaporation (EBV), and plasma etching processes. A low temperature (below 250 °C) is employed to protect the WSe2 and MoS2 channel materials from thermal decomposition during the whole fabrication process. The MoS2 NMOS and WSe2 PMOS device fabricated show an on/off current ratio exceeding 106 and the integrated M3D inverters indicate an average voltage gain of ≈9 at VDD = 2 V. In addition, the integrated M3D inverter demonstrates an ultra-low power consumption of 0.112 nW at a VDD of 1 V. Statistical analysis of the fabricated inverters devices shows their high reliability, rendering them suitable for large-area applications. The successful demonstration of M3D inverters based on large-scale 2D monolayer TMDs indicate their high potential for advancing the application of 2D TMDs in future integrated circuits.

Metabolic adaptations of Microbacterium sediminis YLB-01 in deep-sea high-pressure environments.

The deep-sea environment is an extremely difficult habitat for microorganisms to survive in due to its intense hydrostatic pressure. However, the mechanisms by which these organisms adapt to such extreme conditions remain poorly understood. In this study, we investigated the metabolic adaptations of Microbacterium sediminis YLB-01, a cold and stress-tolerant microorganism isolated from deep-sea sediments, in response to high-pressure conditions. YLB-01 cells were cultured at normal atmospheric pressure and 28 ℃ until they reached the stationary growth phase. Subsequently, the cells were exposed to either normal pressure or high pressure (30 MPa) at 4 ℃ for 7 days. Using NMR-based metabolomic and proteomic analyses of YLB-01 cells exposed to high-pressure conditions, we observed significant metabolic changes in several metabolic pathways, including amino acid, carbohydrate, and lipid metabolism. In particular, the high-pressure treatment stimulates cell division and triggers the accumulation of UDP-glucose, a critical factor in cell wall formation. This finding highlights the adaptive strategies used by YLB-01 cells to survive in the challenging high-pressure environments of the deep sea. Specifically, we discovered that YLB-01 cells regulate amino acid metabolism, promote carbohydrate metabolism, enhance cell wall synthesis, and improve cell membrane fluidity in response to high pressure. These adaptive mechanisms play essential roles in supporting the survival and growth of YLB-01 in high-pressure conditions. Our study offers valuable insights into the molecular mechanisms underlying the metabolic adaptation of deep-sea microorganisms to high-pressure environments. KEY POINTS: • NMR-based metabolomic and proteomic analyses were conducted on Microbacterium sediminis YLB-01 to investigate the significant alterations in several metabolic pathways in response to high-pressure treatment. • YLB-01 cells used adaptive strategies (such as regulated amino acid metabolism, promoted carbohydrate metabolism, enhanced cell wall synthesis, and improved cell membrane fluidity) to survive in the challenging high-pressure environment of the deep sea. • High-pressure treatment stimulated cell division and triggered the accumulation of UDP-glucose, a critical factor in cell wall formation, in Microbacterium sediminis YLB-01 cells.

Imaging features, clinical characteristics and neonatal outcomes of pregnancy luteoma: A case series and literature review.

INTRODUCTION: This study aimed to investigate the imaging features, clinical characteristics and neonatal outcomes of pregnancy luteoma. MATERIAL AND METHODS: We retrospectively analyzed patients with pregnancy luteoma admitted to the First Affiliated Hospital of Sun Yat-sen University between January 2003 and December 2022. We recorded their imaging features, clinical characteristics and neonatal outcomes. Additionally, we reviewed relevant studies in the field. RESULTS: In total, 127 cases were identified, including eight from our hospital and 119 from the literature. Most patients (93/127, 73.23%) were of reproductive age, 20-40 years old, and 66% were parous. Maternal hirsutism or virilization (such as deepening voice, acne, facial hair growth and clitoromegaly) was observed in 29.92% (38/127), whereas 59.06% of patients (75/127) were asymptomatic. Abdominal pain was reported in 13 patients due to compression, torsion or combined ectopic pregnancy. The pregnancy luteomas, primarily discovered during the third trimester (79/106, 74.53%), varied in size ranging from 10 mm to 20 cm in diameter. Seventy-five cases were incidentally detected during cesarean section or postpartum tubal ligation, and 39 were identified through imaging or physical examination during pregnancy. Approximately 26.61% of patients had bilateral lesions. The majority of pregnancy luteomas were solid and well-defined (94/107, 87.85%), with 43.06% (31/72) displaying multiple solid and well-circumscribed nodules. Elevated serum androgen levels (reaching values between 1.24 and 1529 times greater than normal values for term gestation) were observed in patients with hirsutism or virilization, with a larger lesion diameter (P < 0.001) and a higher prevalence of bilateral lesions (P < 0.001). Among the female infants born to masculinized mothers, 68.18% (15/22) were virilized. Information of imaging features was complete in 22 cases. Ultrasonography revealed well-demarcated hypoechoic solid masses with rich blood supply in 12 of 19 cases (63.16%). Nine patients underwent magnetic resonance imaging (MRI) or computed tomography (CT), and six exhibited solid masses, including three with multi-nodular solid masses. CONCLUSIONS: Pregnancy luteomas mainly manifest as well-defined, hypoechoic and hypervascular solid masses. MRI and CT are superior to ultrasonography in displaying the imaging features of multiple nodules. Maternal masculinization and solid masses with multiple nodules on imaging may help diagnose this rare disease.

Safety evaluation of human umbilical cord-mesenchymal stem cells in type 2 diabetes mellitus treatment: A phase 2 clinical trial.

BACKGROUND: Progressive pancreatic ß cell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus (T2DM). Recently, mesenchymal stem cell (MSC) transplantation has emerged as a new therapeutic method due to its ability to promote the regeneration of pancreatic ß cells. However, current studies have focused on its efficacy, and there are few clinical studies on its safety. AIM: To evaluate the safety of human umbilical cord (hUC)-MSC infusion in T2DM treatment. METHODS: An open-label and randomized phase 2 clinical trial was designed to evaluate the safety of hUC-MSC transplantation in T2DM in a Class A hospital. Ten patients in the placebo group received acellular saline intravenously once per week for 3 wk. Twenty-four patients in the hUC-MSC group received hUC-MSCs (1 × 106 cells/kg) intravenously once per week for 3 wk. Diabetic clinical symptoms and signs, laboratory findings, and imaging findings were evaluated weekly for the 1st mo and then at weeks 12 and 24 post-treatment. RESULTS: No serious adverse events were observed during the 24-wk follow-up. Four patients (16.7%) in the hUC-MSC group experienced transient fever, which occurred within 24 h after the second or third infusion; this did not occur in any patients in the placebo group. One patient from the hUC-MSC group experienced hypoglycemic attacks within 1 mo after transplantation. Significantly lower lymphocyte levels (weeks 2 and 3) and thrombin coagulation time (week 2) were observed in the hUC-MSC group compared to those in the placebo group (all P < 0.05). Significantly higher platelet levels (week 3), immunoglobulin levels (weeks 1, 2, 3, and 4), fibrinogen levels (weeks 2 and 3), D-dimer levels (weeks 1, 2, 3, 4, 12, and 24), and neutrophil-to-lymphocyte ratios (weeks 2 and 3) were observed in the hUC-MSC group compared to those in the placebo group (all P < 0.05). There were no significant differences between the two groups for tumor markers (alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 199) or blood fat. No liver damage or other side effects were observed on chest X-ray. CONCLUSION: Our study suggested that hUC-MSC transplantation has good tolerance and high safety in the treatment of T2DM. It can improve human immunity and inhibit lymphocytes. Coagulation function should be monitored vigilantly for abnormalities.

Fc-competent multispecific PDL-1/TIGIT/LAG-3 antibodies potentiate superior anti-tumor T cell response.

The landscape of current cancer immunotherapy is dominated by antibodies targeting PD-1/PD-L1 and CTLA-4 that have transformed cancer therapy, yet their efficacy is limited by primary and acquired resistance. The blockade of additional immune checkpoints, especially TIGIT and LAG-3, has been extensively explored, but so far only a LAG-3 antibody has been approved for combination with nivolumab to treat unresectable or metastatic melanoma. Here we report the development of a PDL1 × TIGIT bi-specific antibody (bsAb) GB265, a PDL1 × LAG3 bsAb GB266, and a PDL1 × TIGIT × LAG3 tri-specific antibody (tsAb) GB266T, all with intact Fc function. In in vitro cell-based assays, these antibodies promote greater T cell expansion and tumor cell killing than benchmark antibodies and antibody combinations in an Fc-dependent manner, likely by facilitating T cell interactions (bridging) with cancer cells and monocytes, in addition to blocking immune checkpoints. In animal models, GB265 and GB266T antibodies outperformed benchmarks in tumor suppression. This study demonstrates the potential of a new generation of multispecific checkpoint inhibitors to overcome resistance to current monospecific checkpoint antibodies or their combinations for the treatment of human cancers.

Review on melanosis coli and anthraquinone-containing traditional Chinese herbs that cause melanosis coli.

Backgrounds: The incidence of melanosis coli (MC) has gradually increased annually, attracting significant attention and efforts into this field. A potential risk for MC is the long-term use of anthraquinone laxatives in patients with constipation. Most traditional cathartic drugs are made from herbs containing anthraquinone compounds. This review aims to provide guidance for the application of traditional Chinese herbs containing anthraquinones for physicians and researchers. Materials and methods: We reviewed risk factors and pathogenesis of MC, and natural anthraquinones isolated from TCM herbs. We searched Pubmed and CNKI databases for literature related to MC with keywords such as"traditional Chinese medicine", "Chinese herbs", "anthraquinones", and "melanosis coli". The literature is current to January 2023 when the searches were last completed. After the literature retrieval, the TCM herbs containing anthraquinones (including component identification and anthraquinone content determination) applied in clinical were selected. According to the collected evidence, we provide a list of herbs containing anthraquinones that could cause MC. Results: We identified 20 herbs belonging to 7 families represented by Polygonaceae, Fabaceae, Rhamnaceae, and Rubiaceae, which may play a role in the pathogenesis of MC. Among these, the herbs most commonly used include Dahuang (Rhei Radix et Rhizome), Heshouwu (Radix Polygoni Multiflori), Huzhang (Rhizoma Polygoni Cuspidati), Juemingzi (Semen Cassiae), Luhui (Aloe) and Qiancao (Rubiae Radix et Rhizoma). Conclusion: Due to a lack of awareness of the chemical composition of TCM herbs, many patients with constipation and even some TCM physicians take cathartic herbal remedies containing abundant anthraquinones to relieve defecation disturbances, resulting in long-term dependence on these herbs, which is potentially associated with most cases of MC. When such treatments are prescribed, TCM physicians should avoid long-term use in large doses to reduce their harm on colonic health. Individuals who take healthcare products containing these herbs should also be under the supervision of a doctor.

Establishment and validation of a cuproptosis-related lncRNA signature that predicts prognosis and potential targeted therapy in hepatocellular carcinoma.

BACKGROUND: Cuproptosis is a recently identified form of programmed cell death and could be a new direction for tumour therapy, and it has important clinical implications. Long non-coding RNAs (lncRNAs) can intervene in diverse biological processes and have a decisive role in hepatocellular carcinoma (HCC). However, how cuproptosis-related lncRNAs (CRLs) participate in regulating HCC has yet to be recognised. This study aimed to establish and validate a prognostic signature of CRLs and to analyse their clinical value in HCC patients. METHODS: To analyse the function of CRLs in the prognosis of HCC, RNA sequencing data, mutation data, and clinically relevant data were collected from the Cancer Genome Atlas Database (TCGA). Then, TCGA cohort was randomly divided into training and test sets. The training set was utilized to define prognostic signature of CRLs using bioinformatics methods. Subsequently, we verified the accuracy of this prognostic signature in the test set. Finally, we performed immune-related analysis, the half-maximal inhibitory concentration (IC50) prediction, gene set enrichment analysis, and tumour mutational burden (TMB) analysis. RESULTS: We established a prognostic signature for the CRLs (SNHG4, AC026412.3, AL590705.3, and CDKN2A-DT). This signature-based risk group displayed an accurate predictive ability for the survival time of patients with HCC. We observed discrepancies in immune cells, immune function, the expression level of genes related to immune checkpoints, and TMB in high- and low-risk groups. CONCLUSION: This CRLs prognostic signature could predict clinical outcomes in patients with HCC as well as the efficacy of targeted and therapy immunotherapy.

Efficacy and safety of gemcitabine and capecitabine combination for patients with previously treated advanced primary pulmonary lymphoepithelioma-like carcinoma: a retrospective single-arm cohort study.

Background: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and unique subtype of non-small cell lung cancer (NSCLC). Studies reporting on salvage treatment for pretreated PLELC are limited. Positive interactions between gemcitabine (GEM) and capecitabine (CAP) have been demonstrated in preclinical studies. In addition, the clinical benefit of the combination has been reported for other malignancies. However, the efficacy and safety of the combination for pretreated PLELC remain unclear. Therefore, we conducted this retrospective study to examine the activity and safety of gemcitabine plus capecitabine (GEM/CAP) combination for previously treated PLELC. Methods: Patients with PLELC at Sun Yat-sen University Cancer Center who received GEM combined with CAP between May 2013 and January 2021 as the second-line therapy or beyond were retrospectively enrolled. Treatment consisted of intravenous GEM (1,000 mg/m2 on days 1 and 8) and oral CAP (1,000 mg/m2 twice daily on days 1-14) every 3 weeks. Evaluation of response was performed every 2 cycles in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. Safety was assessed in accordance with Common Terminology Criteria for Adverse Events version 5.0. Clinical characteristics were collected from medical records. The survival data were obtained by medical records or telephone. Follow-ups were performed until February 3rd, 2021. Results: A total of 16 patients were enrolled in this study. There were 5, 4, 4, and 3 patients treated with GEM/CAP combination as the second-, third-, fourth-, and fifth-line settings, respectively. There were 8 patients with partial response (PR) (50.00%), 6 with stable disease (SD) (37.50%), 2 with progressive disease (PD) (12.50%), and none with complete response (CR). The objective response rate and disease control rate (DCR) were 50.00% and 87.50%, respectively. The most common hematological and nonhematological adverse events (AEs) at any grade were neutropenia (31.25%) and hand-foot syndrome (43.75%). At a median follow-up of 29.3 months with 95% confidence interval (CI) of 20.3 to 38.3 months, the median progression-free survival (PFS) was 9.3 months (95% CI: 6.5-12.1 months). The median overall survival (OS) was 41.5 months (95% CI: 3.1-79.8 months). Conclusions: This retrospective study demonstrated the potential clinical benefit of GEM in combination with CAP for pretreated PLELC. Future multicenter large-scale, prospective studies are warranted.

Multiscale simulation and experimental measurements of the elastic response for constructional steel.

The multiscale elastic response to the macroscopic stress was simulated to reveal the multi-scale correlation of elastic properties of the medium carbon steel. Based on the multiscale correlation constitutive equations derived from this constitutive model, the effective elastic constants (EECs) of medium carbon steel are predicted. In addition, the diffraction elastic constants (DECs) of the constituents of the medium carbon steel are also evaluated. And then, the simple in-situ X-ray diffraction experiments were performed for the measurements of DECs and EECs of treated 35CrMo steel during the four-point bending. Compared with the experimental measurements and different existing models, the results demonstrated that the developed constitutive model was in good agreement with the measured values of the EECs and DECs, and that the feasibility and reliability of the constitutive model used to simulate multiscale elastic response could reveal the correlation between the material and its constitutes.

The effects of Clostridium butyricum on Ira rabbit growth performance, cecal microbiota and plasma metabolome.

Clostridium butyricum (C. butyricum) can provide many benefits for animals' growth performance and gut health. In this study, we investigated the effects of C. butyricum on the growth performance, cecal microbiota, and plasma metabolome in Ira rabbits. A total of 216 Ira rabbits at 32 days of age were randomly assigned to four treatments supplemented with basal diets containing 0 (CG), 200 (LC), 400 (MC), and 600 mg/kg (HC) C. butyricum for 35 days, respectively. In comparison with the CG group, C. butyricum supplementation significantly improved the average daily gain (ADG) and feed conversion rate (FCR) at 53 and 67 days of age (P < 0.05) and digestibilities of crude protein (CP) and crude fiber (CF) at 67 days of age (P < 0.05). The cellulase activity in the HC group was higher respectively by 50.14 and 90.13% at 53 and 67 days of age, than those in the CG groups (P < 0.05). Moreover, at 67 days of age, the diet supplemented with C. butyricum significantly increased the relative abundance of Verrucomicrobia at the phylum level (P < 0.05). Meanwhile, the concentrations of different metabolites, such as amino acids and purine, were significantly altered by C. butyricum (P < 0.05). In addition, 10 different genera were highly correlated with 52 different metabolites at 53-day-old and 6 different genera were highly correlated with 18 different metabolites at 67-day-old Ira rabbits. These findings indicated that the C. butyricum supplementation could significantly improve the growth performance by modifying the cecal microbiota structure and plasma metabolome of weaned Ira rabbits.

Effectiveness and safety of human umbilical cord-mesenchymal stem cells for treating type 2 diabetes mellitus.

BACKGROUND: Progressive pancreatic ß-cell dysfunction is a fundamental part of the pathology of type 2 diabetes mellitus (T2DM). Cellular therapies offer novel opportunities for the treatment of T2DM to improve the function of islet ß-cells. AIM: To evaluate the effectiveness and safety of human umbilical cord-mesenchymal stem cell (hUC-MSC) infusion in T2DM treatment. METHODS: Sixteen patients were enrolled and received 1 × 106 cells/kg per week for 3 wk as intravenous hUC-MSC infusion. The effectiveness was evaluated by assessing fasting blood glucose, C-peptide, normal glycosylated hemoglobin A1c (HbA1c), insulin resistance index (homeostatic model assessment for insulin resistance), and islet ß-cell function (homeostasis model assessment of ß-cell function). The dosage of hypoglycemic agents and safety were evaluated by monitoring the occurrence of any adverse events (AEs). RESULTS: During the entire intervention period, the fasting plasma glucose level was significantly reduced [baseline: 9.3400 (8.3575, 11.7725), day 14 ± 3: 6.5200 (5.2200, 8.6900); P < 0.01]. The HbA1c level was significantly reduced on day 84 ± 3 [baseline: 7.8000 (7.5250, 8.6750), day 84 ± 3: 7.150 (6.600, 7.925); P < 0.01]. The patients' islet ß-cell function was significantly improved on day 28 ± 3 of intervention [baseline: 29.90 (16.43, 37.40), day 28 ± 3: 40.97 (19.27, 56.36); P < 0.01]. The dosage of hypoglycemic agents was reduced in all patients, of whom 6 (50%) had a decrement of more than 50% and 1 (6.25%) discontinued the hypoglycemic agents. Four patients had transient fever, which occurred within 24 h after the second or third infusion. One patient (2.08%) had asymptomatic nocturnal hypoglycemia after infusion on day 28 ± 3. No liver damage or other side effects were reported. CONCLUSION: The results of this study suggest that hUC-MSC infusion can improve glycemia, restore islet ß-cell function, and reduce the dosage of hypoglycemic agents without serious AEs. Thus, hUC-MSC infusion may be a novel option for the treatment of T2DM.

Transjugular intrahepatic portosystemic shunt for the prevention of rebleeding in patients with cirrhosis and portal vein thrombosis: Systematic review and meta-analysis.

Background: Transjugular intrahepatic portosystemic shunt (TIPS) has been performed on patients with cirrhosis and portal vein thrombosis (PVT) to prevent rebleeding; however, the associated evidence is scarce. Hence, the study aimed to evaluate the feasibility and efficacy of TIPS in patients with cirrhosis and PVT and promote personalized treatment in such patients. Methods: Literature was systematically obtained from PubMed, EMBASE, Cochrane Library, and Web of Science. Data from the included studies were extracted, and meta-analyses by the random effects model were used to pool data across studies. Heterogeneity was assessed using Cochran's Q and I2 statistics. The source of heterogeneity was explored using subgroup analyses and meta-regressions. Results: A total of 11 studies comprising 703 patients with cirrhosis and portal vein thrombosis (PVT: complete, 32.2%; chronic, 90.2%; superior mesenteric vein or splenic vein involvement, 55.2%; cavernous transformation, 26.8%) were included. TIPS showed feasibility in 95% of the cases (95% confidence interval [CI]: 89%-99%) with heterogeneity (I2 = 84%, p < 0.01) due to cavernous transformation. The pooled rebleeding rate was 13% (95% CI: 7%-20%) with heterogeneity (I2 = 75%, p < 0.01) explained by chronic PVT and anticoagulation (AC) therapy. Hepatic encephalopathy occurred in 32% of patients. The survival rate, portal vein recanalization rate, and shunt patency rate were 80%, 82%, and 77%, respectively. Conclusion: TIPS is feasible and effectively prevents rebleeding in patients with cirrhosis and PVT, regardless of cavernous transformation of the portal vein. Due to a potentially high risk of rebleeding and no apparent benefits of AC, post-TIPS AC must be employed cautiously. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=258765], identifier [CRD42021258765].