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

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

Remote sensing monitoring and potential distribution analysis of Spartina alterniflora in coastal zone of Guangxi.

In recent years, the continuous expansion of Spartina alterniflora (S. alterniflora) has caused serious damage to coastal wetland ecosystem. Mapping the coverage of S. alterniflora by remote sensing and analyzing its growth pattern pose great importance in controlling the expansion and maintaining the biodiversity of coastal wetlands in Guangxi. This study aimed to use harmonic regression to fit time series data of vegetation indices based on Landsat images, and the phenological features were extracted as the input of random forest model to distinguish S. alterniflora in coastal zone of Guangxi from 2009 to 2020. The influence of natural environmental factors on the distribution of S. alterniflora was evaluated by Maxent model, and the potential distribution was analyzed. The results showed that: (1) Based on the time series data of characteristic indices fitted by harmonic regression, the extraction of phenological features of S. alterniflora identification effect exhibited high accuracy (in the result of 2009, Overall Accuracy [OA] = 97.33%, Kappa = 0.95). (2) During 2009-2020, the S. alterniflora in coastal zone of Guangxi kept proliferating and expanding from east to west. The total area of S. alterniflora continued to increase while the growth rate showed a trend that increased first and then decreased. (3) The Maxent model shows good accuracy in simulating the habitat of S. alterniflora, with a potential distribution area of 14,303.39 hm2. The findings will be beneficial to the understanding of dynamic changes of S. alterniflora in coastal zone of Guangxi and provide a scientific reference for other coastal wetland studies on S. alterniflora expansion.

Structure-Prediction-Oriented Synthesis of Thiophosphates as Promising Infrared Nonlinear Optical Materials.

Oriented synthesis of functional materials is a focus of attention in material science. As one of the most important function materials, infrared nonlinear optical materials with large second harmonic generation effects and broad optical bandgap are in urgent need. In this work, directed by the theoretical structure prediction, the first series of non-centrosymmetric (NCS) alkali-alkaline earth metal [PS4]-based thiophosphates LiCaPS4 (Ama2), NaCaPS4 (P21), KCaPS4 (Pna21), RbCaPS4 (Pna21), CsCaPS4 (Pna21) were successfully synthesized. Comprehensive characterizations reveal that ACaPS4 could be regarded as promising IR NLO materials, exhibiting wide bandgap (3.77-3.86 eV), moderate birefringence (0.027-0.064 at 1064 nm), high laser-induced damage threshold (LIDT, ~10 × AGS), and suitable phase-matching second harmonic generation responses (0.4-0.6 × AGS). Structure-properties analyses illustrate that the Ca-S bonds show non-ignorable covalent feature, and [PS4] together with [CaSn] units play dominant roles to determine the bandgap and SHG response. This work indicates that Li-, Na- and K- analogs may be promising infrared nonlinear optical material candidates, and this is the first successful case of "prediction to synthesis" involving infrared (IR) nonlinear optical (NLO) crystals in the thiophosphate system and may provide a new avenue to the design and oriented synthesis of high-performance function materials in the future.

Improved Lignin Conversion to High-Value Aromatic Monomers through Phase Junction CdS with Coexposed Hexagonal (100) and Cubic (220) Facets.

Photocatalysis has the potential for lignin valorization to generate functionalized aromatic monomers, but its application has been limited by the slow conversion rate and the low selectivity to desirable aromatic products. In this work, we designed the phase junction CdS with coexposed hexagonal (100) and cubic (220) facets to improve the photogenerated charge carriers' transfer efficiency from (100) facet to (220) facet and the hydrogen transfer efficiency for an enhanced conversion rate of lignin to aromatic monomers. Water is found as a sufficient external hydrogen supplier to increase the yields of aromatic monomers. These innovative designs in the reaction system promoted complete conversion of PP-ol to around 94% of aromatic monomers after 1 h of visible light irradiation, which shows the highest reaction rate and selectivity of target products in comparison with previous works. PP-one is a byproduct from the overoxidation of PP-ol and is usually difficult to be further cleaved to acetophenone and phenol as the desirable aromatic monomers. TEA was first identified in this study as a sacrificial electron donor, a hydrogen source, and a mediator to enhance the cleavage of the Cß-O bonds in PP-one. With the assistance of TEA, PP-one can be completely cleaved to desirable aromatic monomer products, and the reaction time is reduced from several hours to 10 min of visible light irradiation.

Cost-Effective Whole Transcriptome Sequencing Landscape and Diagnostic Potential Biomarkers in Active Tuberculosis.

Tuberculosis (TB) is a prevalent and severe infectious disease that poses a significant threat to human health. However, it is frequently disregarded as there are not enough quick and accurate ways to diagnose tuberculosis. Here, we develop a strategy for tuberculosis detection to address the challenges, including an experimental strategy, namely, Double Adapter Directional Capture sequencing (DADCSeq), an easily operated and low-cost whole transcriptome sequencing method, and a computational method to identify hub differentially expressed genes as well as the diagnosis of TB based on whole transcriptome data using DADCSeq on peripheral blood mononuclear cells (PBMCs) from active TB and latent TB or healthy control. Applying our approach to create a robust and stable TB multi-mRNA risk probability model (TBMMRP) that can accurately distinguish active and latent TB patients, including active TB and healthy controls in clinical cohorts, this diagnostic biomarker was successfully validated by several independent cross-platform cohorts with favorable performance in differentiating active TB from latent TB or active TB from healthy controls and further demonstrated superior or similar diagnostic accuracy compared to previous diagnostic markers. Overall, we develop a low-cost and effective strategy for tuberculosis diagnosis; as the clinical cohort increases, we can expand to different disease kinds and learn new features through our disease diagnosis strategy.

ROS-induced imbalance of the miR-34a-5p/SIRT1/p53 axis triggers chronic chondrocyte injury and inflammation.

Osteoarthritis is a chronic degenerative disease based on the degeneration and loss of articular cartilage. Inflammation and aging play an important role in the destruction of the extracellular matrix, in which microRNA (miRNA) is a key point, such as miRNA-34a-5p. Upregulation of miRNA-34a-5p was previously reported in a rat OA model, and its inhibition significantly suppressed interleukin (IL)-1ß-induced apoptosis in rat chondrocytes. However, Oxidative stress caused by reactive oxygen species (ROS) can exacerbate the progression of miRNA regulated OA by mediating inflammatory processes. Thus, oxidative stress effects induced via tert-butyl hydroperoxide (tBHP) in human chondrocytes were assessed in the current research by evaluating mitochondrial ROS production, mitochondrial cyclooxygenase (COX) activity, and cell apoptosis. We also analyzed the activities of antioxidant enzymes including glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD). Additionally, inflammatory factors, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, and IL-24, which contribute to OA development, were detected by enzyme-linked immunosorbent assay (ELISA). The results of this study indicated that miR-34a-5p/silent information regulator 1 (SIRT1)/p53 axis was involved in the ROS-induced injury of human chondrocytes. Moreover, dual-luciferase assay revealed that SIRT1 expression was directly regulated by miR-34a-5p, indicating the presence of a positive feedback loop in the miR-34a-5p/SIRT1/p53 axis that plays an important role in cell survival. However, ROS disrupted the miR-34a-5p/SIRT1/p53 axis, leading to the development of OA, and articular injection of SIRT1 agonist, SRT1720, in a rat model of OA effectively ameliorated OA progression in a dose-dependent manner. Our study confirms that miRNA-34a-5p could participate in oxidative stress responses caused by ROS and further regulate the inflammatory process via the SIRT1/p53 signaling axis, ultimately affecting the onset of OA, thus providing a new treatment strategy for clinical treatment of OA.

The Impact of Sequential Therapies after First-Line Systemic Therapies in Unresectable Hepatocellular Carcinoma.

Background: The therapeutic options for hepatocellular carcinoma (HCC) have greatly expanded recently, and current first-line therapies include sorafenib, lenvatinib, and atezolizumab-bevacizumab. The aim of this study was to investigate the therapeutic efficacy of sequential systemic treatments after progressing to the first-line agent in patients with unresectable HCC. Methods: Data were collected from subjects with HCC, BCLC stage B or C, who received first-line sorafenib, lenvatinib, or atezolizumab-bevacizumab from September 2020 to December 2022. The patients who progressed after first-line therapy were evaluated according to individual clinical status in order to decide whether or not to accept sequential therapy. The clinical baseline characteristics and overall survival (OS) of enrolled patients were collected and further analyzed. Results: Among the 127 enrolled patients, percentage of sequential therapy was 67.9%, 21.6%, and 37.5% in those with tumor progression after first-line sorafenib, lenvatinib, or atezolizumab-bevacizumab, respectively. Acceptance of sequential therapy (HR 0.46, p = 0.041) and presentation of ALBI grade I (HR 0.36, p = 0.002) had a significantly positive impact on OS. Pre-treatment ALBI grade had a significant impact on the decision to accept sequential therapy in patients with progressed HCC. Conclusions: The patients who were able to undergo sequential therapy had a better survival outcome compared to those who received only one agent, and the pre-treatment ALBI level might be regarded as a cornerstone tool to assess survival outcomes in patients undergoing treatment for HCC.

Identification of CFH and FHL2 as biomarkers for idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal disease of unknown etiology with a poor prognosis, characterized by a lack of effective diagnostic and therapeutic interventions. The role of immunity in the pathogenesis of IPF is significant, yet remains inadequately understood. This study aimed to identify potential key genes in IPF and their relationship with immune cells by integrated bioinformatics analysis and verify by in vivo and in vitro experiments. Methods: Gene microarray data were obtained from the Gene Expression Omnibus (GEO) for differential expression analysis. The differentially expressed genes (DEGs) were identified and subjected to functional enrichment analysis. By utilizing a combination of three machine learning algorithms, specific genes associated with idiopathic pulmonary fibrosis (IPF) were pinpointed. Then their diagnostic significance and potential co-regulators were elucidated. We further analyzed the correlation between key genes and immune infiltrating cells via single-sample gene set enrichment analysis (ssGSEA). Subsequently, a single-cell RNA sequencing data (scRNA-seq) was used to explore which cell types expressed key genes in IPF samples. Finally, a series of in vivo and in vitro experiments were conducted to validate the expression of candidate genes by western blot (WB), quantitative real-time PCR (qRT-PCR), and immunohistochemistry (IHC) analysis. Results: A total of 647 DEGs of IPF were identified based on two datasets, including 225 downregulated genes and 422 upregulated genes. They are closely related to biological functions such as cell migration, structural organization, immune cell chemotaxis, and extracellular matrix. CFH and FHL2 were identified as key genes with diagnostic accuracy for IPF by three machine learning algorithms. Analysis using ssGSEA revealed a significant association of both CFH and FHL2 with diverse immune cells, such as B cells and NK cells. Further scRNA-seq analysis indicated CFH and FHL2 were specifically upregulated in human IPF tissues, which was confirmed by in vitro and in vivo experiments. Conclusion: In this study, CFH and FHL2 have been identified as novel potential biomarkers for IPF, with potential diagnostic utility in future clinical applications. Subsequent investigations into the functions of these genes in IPF and their interactions with immune cells may enhance comprehension of the disease's pathogenesis and facilitate the identification of therapeutic targets.

Fecal Carriage of Multidrug-Resistant Organisms Increases the Risk of Hepatic Encephalopathy in Cirrhotic Patients: Insights from Gut Microbiota and Metabolite Features.

Background: Impact of fecal colonization by multidrug-resistant organisms (MDROs) on changes in gut microbiota and associated metabolites, as well as its role in cirrhosis-associated outcomes, has not been thoroughly investigated. Methods: Eighty-eight cirrhotic patients and 22 healthy volunteers were prospectively enrolled with analysis conducted on plasma metabolites, fecal MDROs, and microbiota. Patients were followed for a minimum of one year. Predictive factors for cirrhosis-associated outcomes were identified using Cox proportional hazards regression models, and risk factors for fecal MDRO carriage were assessed using logistic regression model. Correlations between microbiota and metabolic profiles were evaluated through Spearman's rank test. Results: Twenty-nine (33%) cirrhotic patients exhibited MDRO carriage, with a notably higher rate of hepatic encephalopathy (HE) in MDRO carriers (20.7% vs. 3.2%, p = 0.008). Cox regression analysis identified higher serum lipopolysaccharide levels and fecal MDRO carriage as predictors for HE development. Logistic regression analysis showed that MDRO carriage is an independent risk factor for developing HE. Microbiota analysis showed a significant dissimilarity of fecal microbiota between cirrhotic patients with and without MDRO carriage (p = 0.033). Thirty-two metabolites exhibiting significantly different expression levels among healthy controls, cirrhotic patients with and without MDRO carriage were identified. Six of the metabolites showed correlation with specific bacterial taxa expression in MDRO carriers, with isoaustin showing significantly higher levels in MDRO carriers experiencing HE compared to those who did not. Conclusion: Fecal MDRO carriage is associated with altered gut microbiota, metabolite modulation, and an elevated risk of HE occurrence within a year.

Brief psychotic disorder related to areca nut use: a case report.

Background: Areca Nut (AN) is the fourth most commonly abused drug after nicotine, ethanol, and caffeine, due to its psychoactive properties provided by bioactive substances. Although previous studies have demonstrated AN's anxiolytic-like activity and potential benefits in ameliorating symptoms of depression and schizophrenia, there remains limited awareness regarding its association with brief psychotic disorder. Case presentation: This case report presents the clinical profile of a 30-year-old male patient with a history of betel nut chewing for the past 2 years, who exhibited sudden onset delusions, hallucinations, and disorganized speech and behavior upon increasing the dosage of betel nut consumption. The patient displayed a positive response to antipsychotic treatment, and symptoms resolved upon discontinuation of betel nut consumption. However, one month after discharge, the patient experienced a recurrence of auditory hallucinations upon resuming betel nut chewing. Through counseling and support, the importance of abstaining from betel nut use and maintaining medication compliance was emphasized, resulting in no recurrence of psychotic symptoms during the six-month follow-up. Conclusions: This case report highlights the related role of betel nut with brief psychotic disorder, especially when the chewing dosage is abruptly increased. It underscores the importance of considering betel nut as a potential precipitant related to acute psychiatric disorders in clinical settings.

Structural optimization of Moracin M as novel selective phosphodiesterase 4 inhibitors for the treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and high mortality lung disease. Although the antifibrotic drugs pirfenidone and nintedanib could slow the rate of lung function decline, the usual course of the condition is inexorably to respiratory failure and death. Therefore, new approaches and novel therapeutic drugs for the treatment of IPF are urgently needed. And the selective PDE4 inhibitor has in vivo and in vitro anti-fibrotic effects in IPF models. But the clinical application of most PDE4 inhibitors are limited by their unexpected and severe side effects such as nausea, vomiting, and diarrhea. Herein, structure-based optimizations of the natural product Moracin M resulted in a novel a novel series of 2-arylbenzofurans as potent PDE4 inhibitors. The most potent inhibitor L13 has an IC50 of 36 ± 7 nM with remarkable selectivity across the PDE families and administration of L13·citrate (10.0 mg/kg) exhibited comparable anti-pulmonary fibrosis effects to pirfenidone (300 mg/kg) in a bleomycin-induced IPF mice model, indicate that L13 is a potential lead for the treatment of IPF.

Tuning the optoelectronic properties of emerging solar absorbers through cation disorder engineering.

Chalcogenide solar absorbers, such as AgBiS2 and kesterites, have gained a resurgence of interest recently, owing to their high stability compared to metal-halide compounds, as well as their rising efficiencies in photovoltaic devices. Although their optical and electronic properties are conventionally tuned through the composition and structure, cation disorder has increased in prominence as another important parameter that influences these properties. In this minireview, we define cation disorder as the occupation of a cation crystallographic site with different species, and the homogeneity of this cation disorder as how regular the alternation of species in this site is. We show that cation disorder is not necessarily detrimental, and can lead to increases in absorption coefficient and reductions in bandgap, enabling the development of ultrathin solar absorbers for lightweight photovoltaics. Focusing on kesterites and ABZ2 materials (where A = monovalent cation, B = divalent cation, and Z is a chalcogenide anion), we discuss how the degree and homogeneity of cation disorder influences the optical properties, charge-carrier transport and photovoltaic performance of these materials, as well as how cation disorder could be tuned and quantified. We finish with our perspectives on the important questions moving forward in making use of cation disorder engineering as a route to achieve more efficient solar absorbers.

Ketogenic diet time-dependently prevents NAFLD through upregulating the expression of antioxidant protein metallothionein-2.

BACKGROUND & AIMS: The past few decades have witnessed a rapid growth in the prevalence of nonalcoholic fatty liver disease (NAFLD). While the ketogenic diet (KD) is considered for managing NAFLD, the safety and efficacy of the KD on NAFLD has been a controversial topic. Here, we aimed to investigate the effect of KD of different durations on metabolic endpoints in mice with NAFLD and explore the underlying mechanisms. METHODS: NAFLD mice were fed with KD for 1, 2, 4 and 6 weeks, respectively. The blood biochemical indexes (blood lipids, AST, ALT and etc.) and liver fat were measured. The LC-MS/MS based proteomic analysis was performed on liver tissues. Metallothionein-2 (MT2) was knocked down with adeno-associated virus (AAV) or small interfering RNA (siRNA) in NAFLD mice and AML-12 cells, respectively. H&E, BODIPY and ROS staining were performed to examine lipid deposition and oxidative stress. Furthermore, MT2 protein levels, nucleus/cytoplasm distribution and DNA binding activity of peroxisome proliferators-activated receptors α (PPARα) were evaluated. RESULTS: KD feeding for 2 weeks showed the best improvement on NAFLD phenotype. Proteomic analysis revealed that MT2 was a key candidate for different metabolic endpoints of NAFLD affected by different durations of KD feeding. MT2 knockdown in NAFLD mice blocked the effects of 2 weeks of KD feeding on HFD-induced steatosis. In mouse primary hepatocytes and AML-12 cells, MT2 protein levels were induced by ß-hydroxybutyric acid (ß-OHB). MT2 Knockdown blunted the effects of ß-OHB on alleviating PA-induced lipid deposition. Mechanistically, 2 weeks of KD or ß-OHB treatment reduced oxidative stress and upregulated the protein levels of MT2 in nucleus, which subsequently increased its DNA binding activity and PPARα protein expression. CONCLUSIONS: Collectively, these findings indicated that KD feeding prevented NAFLD in a time dependent manner and MT2 is a potential target contributing to KD improvement on steatosis.

Physical frailty, genetic predisposition, and incident dementia: a large prospective cohort study.

Physical frailty and genetic factors are both risk factors for increased dementia; nevertheless, the joint effect remains unclear. This study aimed to investigated the long-term relationship between physical frailty, genetic risk, and dementia incidence. A total of 274,194 participants from the UK Biobank were included. We applied Cox proportional hazards regression models to estimate the association between physical frailty and genetic and dementia risks. Among the participants (146,574 females [53.45%]; mean age, 57.24 years), 3,353 (1.22%) new-onset dementia events were recorded. Compared to non-frailty, the hazard ratio (HR) for dementia incidence in prefrailty and frailty was 1.396 (95% confidence interval [CI], 1.294-1.506, P < 0.001) and 2.304 (95% CI, 2.030-2.616, P < 0.001), respectively. Compared to non-frailty and low polygenic risk score (PRS), the HR for dementia risk was 3.908 (95% CI, 3.051-5.006, P < 0.001) for frailty and high PRS. Furthermore, among the participants, slow walking speed (HR, 1.817; 95% CI, 1.640-2.014, P < 0.001), low physical activity (HR, 1.719; 95% CI, 1.545-1.912, P < 0.001), exhaustion (HR, 1.670; 95% CI, 1.502-1.856, P < 0.001), low grip strength (HR, 1.606; 95% CI, 1.479-1.744, P < 0.001), and weight loss (HR, 1.464; 95% CI, 1.328-1.615, P < 0.001) were independently associated with dementia risk compared to non-frailty. Particularly, precise modulation for different dementia genetic risk populations can also be identified due to differences in dementia risk resulting from the constitutive pattern of frailty in different genetic risk populations. In conclusion, both physical frailty and high genetic risk are significantly associated with higher dementia risk. Early intervention to modify frailty is beneficial for achieving primary and precise prevention of dementia, especially in those at high genetic risk.

Degradation of reactive red (B-3BF) dye wastewater using UV irradiation (254/185 nm) with sodium persulfate in a pilot UV device.

Two low-pressure ultraviolet (UV) lamps at 185/254 nm with sodium persulfate in a pilot UV device were utilized for the degradation of reactive red (B-3BF) dye wastewater compared with two UV lamps at 185/185 nm and two UV lamps at 254/254 nm. The degradation performances of UV irradiation (254/185 nm) with sodium persulfate under different degradation times, flow rates, initial pH, initial Na2S2O8 concentrations and initial dye concentrations were investigated. The experimental results illustrated that the degradation percentage of B-3BF dye could reduce to 90.42% with the energy consumption of 85.1 kWh/kg and the residual dye concentration of 1.92 mg/L by UV irradiation (254/185 nm) with initial Na2S2O8 concentration of 1.5 mmol/L and initial dye concentration of 20 mg/L. In addition, degradation performance of B-3BF dye wastewater by UV irradiation (254/185 nm) with sodium persulfate was more effective than those of UV irradiation (254/254 nm) and UV irradiation (185/185 nm). Therefore UV irradiation (254/185 nm) with sodium persulfate was promising for the degradation of B-3BF dye wastewater.

Oxytocin infusion dose-response to maintain uterine tone in obese elective cesarean patients: a randomized controlled trial.

Background: For cesarean delivery (CD), the 90% effective dosage (ED90) of oxytocin for a first bolus has been established. It is not yet known how much oxytocin to inject into obese women undergoing elective discectomy to keep their uterine tone (UT) appropriate. We hypothesized that patients who are overweight need a greater dose of oxytocin infusion; thus, we aimed to determine how the dose-response curve for oxytocin infusion changes following an initial 1 international unit (IU) bolus in obese women undergoing elective CD. Methods: One hundred parturients with a body mass index (BMI) greater than 30 kg/m2 were randomly assigned to receive an infusion rate of 14, 18, 22, or 26 IU/h of oxytocin. When the uterine palpation is as hard as touching the forehead or tip of the nose, it is considered sufficient UT according to the criteria used by obstetricians. The median effective dose (ED50) and ED90 values were determined using probit analysis. Results: We found the ED50 and ED90 values for the infusion dose of oxytocin were around 11.0 IU/h and 19.1 IU/h, respectively. Each group had a different number of parturients who needed rescued oxytocin: 14 IU/h for six, 18 IU/h for three, one for 22 IU/h, and none for 26 IU/h. The correlation between the frequency of rescued oxytocin administration and the amount of oxytocin infusion needed to avoid uterine atony was statistically significant (p = 0.02). Conclusion: The present research showed that the most effective dosage of oxytocin infusion for obese parturients undergoing elective CD is 19.1 IU/h, following an initial loading dose of 1 IU. Patients with obesity should receive a greater dosage of prophylactic oxytocin, and further studies comparing patients with and without obesity (with higher BMI) are required. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=159951, identifier ChiCTR2200059582.

Mitigating treatment failure of pulmonary pre-extensively drug-resistant tuberculosis: The role of new and repurposed drugs.

BACKGROUND: Pre-extensively drug-resistant tuberculosis (pre-XDR-TB), defined as multidrug-resistant TB (MDR-TB) with additional resistance to any fluoroquinolone (FQ) is difficult to treat. We assessed whether the use of new or repurposed drugs (bedaquiline, delamanid, linezolid, carbapenem, clofazimine, pretomanid) mitigated treatment failure of pre-XDR-TB. METHODS: MDR-TB patients managed in the Taiwan MDR-TB consortium between July 2009-December 2019 were eligible. Treatment outcomes at 30 months were assessed. Logistic regression models were constructed to investigate factors associated with treatment outcomes. RESULTS: 109 patients with FQ-resistant MDR-TB and 218 patients with FQ-susceptible MDR-TB were included. 60 (55.1%) patients with FQ-resistant MDR-TB and 63 (28.9%) patients with FQ-susceptible MDR-TB have been treated with new or repurposed drugs (p < 0.01). Of the 218 patients with FQ-susceptible MDR-TB, 187 (85.8%) had treatment success, 30 (13.8%) died, no treatment failure, and 1 (0.5%) was loss-to-follow-up; of the 109 patients with FQ-resistant MDR-TB, 78 (71.6%) had treatment success, 21 (19.3%) died, 9 (8.3%) had treatment failure, and 1 (0.9%) was loss-to-follow-up (p < 0.01). The use of new or repurposed drugs was not associated with treatment outcomes among patients with FQ-susceptible MDR-TB. No patients with FQ-resistant MDR-TB treated with ≥2 new or repurposed drugs within 6 months of treatment initiation had treatment failure (p = 0.03). Patients with FQ-resistant MDR-TB treated with 1 new or repurposed drugs was more likely to have treatment failure as compared with patients not treated with new or repurposed drugs (adjOR 7.06, 95% CI 1.72-29.06). CONCLUSIONS: Proper use of new or repurposed anti-TB drugs can mitigate treatment failure in FQ-resistant MDR-TB.

Interceed combined with bone marrow mesenchymal stem cells improves endometrial receptivity of intrauterine adhesion.

Background: This study aimed to investigate the impact of intrauterine adhesions (IUA) therapy and endometrial receptivity by implanting autologous bone marrow mesenchymal stem cells (BMSCs) into the Interceed and subsequently placing them in the uterine cavity of rats. Methods: Fifty rats were divided into 5 groups according to the random number table method (10 rats in each group). Following the development of the IUA model through mechanical injury, the animals were categorized into different treatment groups: the IUA model (intrauterine perfusion of saline), Interceed therapy (intrauterine placement of Interceed), BMSCs therapy (intrauterine perfusion of BMSCs), BMSCs + Interceed therapy (intrauterine placement of BMSCs + Interceed), and a control group (intrauterine perfusion of saline). The Hematoxylin-eosin (HE) staining technique was employed to identify and assess the pathological alterations in the endometrium. Additionally, it facilitated the quantification of endometrial glands and the determination of endometrial thickness. Masson staining was used to detect fibrosis in rat uterus. The number of microvascular density (MVD) was detected by immunohistochemistry (IHC). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were used to detect the levels of leukemia inhibitory factor (LIF), integrin ανß3, and vascular endothelial growth factor (VEGF) in uterine tissue. Male and female rats were combined in cages for reproductive and conception evaluation. Results: In comparison to the control, the number of endometrial glands in the IUA model was significantly reduced, and the degree of endometrial thinning and fibrosis was significantly increased (p < 0.05). Compared with the IUA model, the number of endometrial glands did not exhibit any significant alterations in endometrial thickness and MVD number. The expressions of LIF, integrin ανß3, and VEGF in the uterine tissue were not significantly improved with Interceed therapy, resulting in no significant improvement in the pregnancy rate (p > 0.05). The number of endometrial glands, endometrial thickness, and MVD in the BMSCs therapy group were significantly increased. Moreover, the expressions of LIF, integrin ανß3, and VEGF in uterine tissue exhibited a significant increase, leading to a comparatively higher pregnancy rate (p < 0.05). In the BMSCs + Interceed therapy group, the number of endometrial glands, endometrial thickness, and MVD were significantly increased, and the expressions of LIF, integrin ανß3, and VEGF in uterine tissue were significantly increased as well, along with a corresponding rise in the pregnancy rate (p < 0.05). Conclusion: The intrauterine placement of Interceed combined with BMSCs in IUA rats can thicken the damaged endometrium, increase the number of glands, promote endometrial angiogenesis, improve endometrial receptivity, and increase the rate of pregnancy in IUA rats.

The immune landscape of sepsis and using immune clusters for identifying sepsis endotypes.

Background: The dysregulated immune response to sepsis still remains unclear. Stratification of sepsis patients into endotypes based on immune indicators is important for the future development of personalized therapies. We aimed to evaluate the immune landscape of sepsis and the use of immune clusters for identifying sepsis endotypes. Methods: The indicators involved in innate, cellular, and humoral immune cells, inhibitory immune cells, and cytokines were simultaneously assessed in 90 sepsis patients and 40 healthy controls. Unsupervised k-means cluster analysis of immune indicator data were used to identify patient clusters, and a random forest approach was used to build a prediction model for classifying sepsis endotypes. Results: We depicted that the impairment of innate and adaptive immunity accompanying increased inflammation was the most prominent feature in patients with sepsis. However, using immune indicators for distinguishing sepsis from bacteremia was difficult, most likely due to the considerable heterogeneity in sepsis patients. Cluster analysis of sepsis patients identified three immune clusters with different survival rates. Cluster 1 (36.7%) could be distinguished from the other clusters as being an "effector-type" cluster, whereas cluster 2 (34.4%) was a "potential-type" cluster, and cluster 3 (28.9%) was a "dysregulation-type" cluster, which showed the lowest survival rate. In addition, we established a prediction model based on immune indicator data, which accurately classified sepsis patients into three immune endotypes. Conclusion: We depicted the immune landscape of patients with sepsis and identified three distinct immune endotypes with different survival rates. Cluster membership could be predicted with a model based on immune data.