Efficacy and Safety of Pemafibrate, a Novel Selective PPARα Modulator in Chinese Patients with Dyslipidemia: A Double-Masked, Randomized, Placebo- and Active-Controlled Comparison Trial.

AIMS: Pemafibrate substantially lowers serum triglyceride (TG) levels and increases high-density lipoprotein cholesterol (HDL-C) levels primarily in Japan, but it has not been evaluated in China. We aimed to confirm the efficacy and safety of pemafibrate in Chinese patients with hypertriglyceridemia and low HDL-C levels by comparing placebo and fenofibrate. METHODS: A multicenter, double-masked trial was conducted in China involving 344 patients with high TG and low HDL-C levels randomly assigned to one of four groups: pemafibrate 0.2 mg/d, pemafibrate 0.4 mg/d, fenofibrate 200 mg/d, or placebo for 12 weeks. The primary endpoint was the percentage change in fasting TG levels. RESULTS: The percentage change in TG levels from baseline was -34.1%, -44.0%, -30.5%, and 6.5% in the pemafibrate 0.2 mg/d, pemafibrate 0.4 mg/d, fenofibrate 200 mg/d, and placebo groups, respectively. Pemafibrate 0.4 mg/d significantly reduced TG levels compared with that in both placebo (p＜0.0001) and fenofibrate groups (p=0.0083). Significant improvements in HDL-C, remnant cholesterol, and apolipoprotein A1 levels were also observed with both doses of pemafibrate than with the placebo. Pemafibrate showed significantly smaller changes in alanine aminotransferase, aspartate aminotransferase, and serum creatinine levels than those with fenofibrate. CONCLUSIONS: In Chinese patients, pemafibrate exhibited superior efficacy in improving TG levels and enhanced hepatic and renal safety compared to fenofibrate. Thus, pemafibrate may represent a promising therapeutic option for dyslipidemia in Chinese patients.

Combined healthy lifestyles and risk of depressive symptoms: A baseline survey in China.

BACKGROUND: Little evidence exists about whether a combination of healthy lifestyle factors is associated with a lower risk of depressive symptoms among Chinese population. We aimed to investigate the association between combined healthy lifestyle factors and risk of depressive symptoms. METHODS: We conducted a baseline survey from July 2021 to December 2023, including 53,642 Chinese adults from general population. A healthy lifestyle score was constructed based on six lifestyle factors (physical activity, smoking status, alcohol consumption, diet, sleep duration, and body mass index). Logistic regression models were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) adjusted for confounding variables. RESULTS: Each additional healthy lifestyle score was associated with a 20 % lower risk of having depressive symptoms (OR (95 % CI): 0.80 (0.78-0.81)). Compared with individuals with ≤2 healthy lifestyle factors, individuals with all the six healthy lifestyle factors had a 58 % reduced risk of having depressive symptoms (0.42 (0.37-0.47)). After stratification by gender, education and urbanization, the significant inverse association with healthy lifestyle score was stronger in women, individuals with high education, and urban residents. Besides, the significant negative association between healthy lifestyle score and depressive symptoms remained for different severity of depressive symptoms. LIMITATIONS: Given the cross-sectional nature of data, we cannot make causal inferences. CONCLUSIONS: Our study indicated that adherence to healthy lifestyle factors was associated with a reduced risk of having depressive symptoms among Chinese adults. The observed associations were modified by gender, education and urbanization. These findings warrant further verification in interventional studies.

Source and level of dietary iron influence semen quality by affecting inflammation, oxidative stress and iron utilization levels in boars.

BACKGROUND: Boars fed a mixed form of inorganic and organic iron in excess of the NRC recommended levels still develop anemia, which suggested that the current level and form of iron supplementation in boar diets may be inappropriate. Therefore, 56 healthy Topeka E line boars aged 15-21 months were randomly divided into 5 groups: basal diet supplemented with 96 mg/kg ferrous sulfate (FeSO4) and 54 mg/kg glycine chelated iron (Gly-Fe, control); 80 mg/kg or 115 mg/kg Gly-Fe; 80 mg/kg or 115 mg/kg methionine hydroxyl analogue chelated iron (MHA-Fe, from Calimet-Fe) for 16 weeks. The effects of dietary iron supplementation with different sources and levels on semen quality in boars were investigated. RESULTS: 1) Serum Fe and hemoglobin concentrations were not affected by reduced dietary iron levels in the 80 mg/kg or 115 mg/kg Gly-Fe and MHA-Fe groups compared with the control group (P > 0.05). 2) Serum interleukin-6 (IL-6) and sperm malondialdehyde (MDA) levels in the 80 mg/kg or 115 mg/kg MHA-Fe groups were lower than those in the control group (P < 0.05), and higher serum superoxide dismutase levels and lower MDA levels in the 115 mg/kg MHA-Fe group (P < 0.05). 3) Boars in the 80 mg/kg or 115 mg/kg Gly-Fe and MHA-Fe groups had lower serum hepcidin (P < 0.01), ferritin (P < 0.05), and transferrin receptor (P < 0.01) concentrations, and boars in the 115 mg/kg MHA-Fe group had higher seminal plasma Fe concentrations compared with the control group. 4) Boars in the 80 mg/kg and 115 mg/kg MHA-Fe groups had lower abnormal sperm rate and in situ oscillating sperm ratio compared to the control group at weeks 12 and/or 16 of the trial. However, the effect of Gly-Fe on improving semen quality in boars was not evident. 5) Serum IL-6 level was positively correlated with hepcidin concentration (P < 0.05), which in turn was significantly positively correlated with abnormal sperm rate (P < 0.05). Furthermore, significant correlations were also found between indicators of iron status and oxidative stress and semen quality parameters. CONCLUSIONS: Dietary supplementation with 80 mg/kg or 115 mg/kg MHA-Fe did not induce iron deficiency, but rather reduced serum inflammatory levels and hepcidin concentration, alleviated oxidative stress, increased body iron utilization, and improved semen quality in adult boars.

Vitamin C Alleviates the Risk of Gestational Diabetes Mellitus Associated With Exposure to Metals.

Background: Exposure to heavy metals has been suggested to increase the risk of gestational diabetes mellitus (GDM) through the oxidative stress pathway. The study is aimed at examining whether vitamin C could modify the association between exposure to heavy metals and risk of GDM. Methods: We conducted a case-control study in Taiyuan, China, with 776 GDM cases and 776 controls. Data on vitamin C intake from diet and supplements were collected through questionnaires. Concentrations of metals in participants' blood were measured using inductively coupled plasma-mass spectrometry (ICP-MS). Unconditional logistic regression models were applied to estimate effect modification of vitamin C on the association between heavy metals and GDM. Results: Women with higher blood levels of mercury (Hg) (odds ratio (OR) = 2.36, 95% confidence interval (CI): 1.43, 3.92 and 2.04, 95% CI: 1.20, 3.46 for the second and third vs. the first tertile) and arsenic (As) (OR = 2.46, 95% CI: 1.37, 4.43 and 2.16, 95% CI: 1.12, 4.17 for the second and third vs. the first tertile) exposure were associated with increased risk of GDM among women without vitamin C supplement use and having dietary vitamin C intake < 85 mg/day. We found no significant association with metals among women who took vitamin C supplements and/or dietary vitamin C ≥ 85 mg/day. Significant interactions were observed between vitamin C and exposures to metals (i.e., Hg and As) on the risk of GDM (P interaction = 0.048 and 0.045, respectively). Conclusions: Our study, for the first time, suggests that vitamin C supplement use or higher dietary vitamin C intake during preconception and early pregnancy could alleviate the risk of GDM associated with exposure to As and Hg. The results warrant further investigation.

[Expression of the D930020B18Rik gene in the mouse testis during spermatogenesis: Characteristics and potential role].

OBJECTIVE: To investigate the expression pattern of the D930020B18Rik gene in the testis of the mouse in different stages of development and its possible role in spermatogenesis. METHODS: Using gene expression profile microarray, we identified highly expressed D930020B18Rik in the mouse testis and analyzed the expression pattern of the gene by qPCR, immunohistochemistry, Western blot and immunofluorescence staining, and verified its function and molecular mechanism using bioinformatics analysis, dual-luciferase reporter assay and cell cycle synchronization. RESULTS: The expression of the D930020B18Rik gene remained low in the testis of the mouse and mainly localized in the cytoplasm of spermatogonia during the first 2 postnatal weeks (PNW), increased from the 3rd PNW to sexual maturity, localized in the cytoplasm of spermatogonia and the nuclei of round and elongated spermatids, but was absent in the nuclei of mature sperm. Phylogenetic analysis showed that the D930020B18Rik protein sequence was highly conserved in mammals. Gene set enrichment analysis indicated that D930020B18Rik and its homologous protein might be involved in regulating spermatogenesis of mammals by participating in nucleoplasmic condensation (normalized enrichment score ï¼»NESï¼½ = 1.652, P < 0.01, false discovery rate ï¼»FDRï¼½ = 0.153), meiosis (NES = 1.960, P < 0.01, FDR = 0.001) and formation of microtubule cytoskeleton during mitosis (NES = 1.903, P < 0.01, FDR = 0.009). Dual-luciferase reporter assay revealed that the transcription factors klf5 and foxo1 could identify and bind D930020B18Rik promoters and perform the function of positive or negative transcriptional regulation. CONCLUSION: The D930020B18Rik gene is expressed in the mouse testis in a time- and location-specific manner, highly associated with spermiogenesis, mainly localized in the nuclei of germ cells, and may be involved in the meiosis of spermatocytes and spermiogenesis.

Investigating functional mechanisms in the Co-biodegradation of lignite and guar gum under the influence of salinity.

The biodegradation of guar gum by microorganisms sourced from coalbeds can result in low-temperature gel breaking, thereby reducing reservoir damage. However, limited attention has been given to the influence of salinity on the synergistic biodegradation of coal and guar gum. In this study, biodegradation experiments of guar gum and lignite were conducted under varying salinity conditions. The primary objective was to investigate the controlling effects and mechanisms of salinity on the synergistic biodegradation of lignite and guar gum. The findings revealed that salinity had an inhibitory effect on the biomethane production from the co-degradation of lignite and guar gum. The biomethane production declined with increasing salinity levels, decreasing from 120.9 mL to 47.3 mL. Even under 20 g/L salt stress conditions, bacteria in coalbeds could effectively break the gel and the viscosity decreased to levels below 5 mPa s. As salinity increased, the removal rate of soluble chemical oxygen demand (SCOD) decreased from 55.63% to 31.17%, and volatile fatty acids (VFAs) accumulated in the digestion system. High salt environment reduces the intensity of each fluorescence peak. Alterations in salinity led to changes in microbial community structure and diversity. Under salt stress, there was an increased relative abundance of Proteiniphilum and Methanobacterium, ensuring the continuity of anaerobic digestion. Hydrogentrophic methanogens exhibited higher salt tolerance compared to acetoclastic methanogens. These findings provide experimental evidence supporting the use of guar gum fracturing fluid in coalbeds with varying salinity levels.

Investigation of the Rapid Emergence of Colistin Resistance in a Newborn Infected with KPC-2-Producing Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae.

OBJECTIVES: Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKp) poses a significant threat to public health. This study reports an infection related to hv-CRKp in a premature infant and reveals its colistin resistance and evolutionary mechanisms within the host. METHODS: Three KPC-producing CRKp strains were isolated from a patient with sepsis and CRKp osteoarthritis who had been receiving colistin antimicrobial therapy. The minimum inhibitory concentrations (MICs) of ceftazidime, ceftazidime-avibactam (CAZ-AVI), meropenem, imipenem, tigecycline, amikacin, minocycline, sulfamethoxazole/trimethoprim, ciprofloxacin, levofloxacin, aztreonam, cefepime, cefoperazone/sulbactam, piperacillin/tazobactam, and colistin were determined using the microbroth dilution method. The whole-genome sequencing analysis was conducted to determine the sequence types (STs), virulence genes, and antibiotic resistance genes of the three CRKp strains. RESULTS: Whole-genome sequencing revealed that all three CRKp strains belonged to the ST11 clone and carried a plasmid encoding blaKPC-2. The three strains all possessed the iucABCDiutA virulence cluster, peg-344 gene, and rmpA/rmpA2 genes, defining them as hv-CRKp. Further experiments and whole-genome analysis revealed that a strain of K. pneuomniae had developed resistance to colistin. The mechanism found to be responsible for colistin resistance was a deletion mutation of approximately 9000 bp including the mgrB gene. CONCLUSION: This study characterizes colistin resistance of the ST11 clone hv-CRKp during colistin treatment and its rapid evolution within the host.

A review on 4D cone-beam CT (4D-CBCT) in radiation therapy: Technical advances and clinical applications.

Cone-beam CT (CBCT) is the most commonly used onboard imaging technique for target localization in radiation therapy. Conventional 3D CBCT acquires x-ray cone-beam projections at multiple angles around the patient to reconstruct 3D images of the patient in the treatment room. However, despite its wide usage, 3D CBCT is limited in imaging disease sites affected by respiratory motions or other dynamic changes within the body, as it lacks time-resolved information. To overcome this limitation, 4D-CBCT was developed to incorporate a time dimension in the imaging to account for the patient's motion during the acquisitions. For example, respiration-correlated 4D-CBCT divides the breathing cycles into different phase bins and reconstructs 3D images for each phase bin, ultimately generating a complete set of 4D images. 4D-CBCT is valuable for localizing tumors in the thoracic and abdominal regions where the localization accuracy is affected by respiratory motions. This is especially important for hypofractionated stereotactic body radiation therapy (SBRT), which delivers much higher fractional doses in fewer fractions than conventional fractionated treatments. Nonetheless, 4D-CBCT does face certain limitations, including long scanning times, high imaging doses, and compromised image quality due to the necessity of acquiring sufficient x-ray projections for each respiratory phase. In order to address these challenges, numerous methods have been developed to achieve fast, low-dose, and high-quality 4D-CBCT. This paper aims to review the technical developments surrounding 4D-CBCT comprehensively. It will explore conventional algorithms and recent deep learning-based approaches, delving into their capabilities and limitations. Additionally, the paper will discuss the potential clinical applications of 4D-CBCT and outline a future roadmap, highlighting areas for further research and development. Through this exploration, the readers will better understand 4D-CBCT's capabilities and potential to enhance radiation therapy.

Effects of basic amino acids on heterocyclic amines and quality characteristics of fried beef patties at low NaCl level.

The impact of basic amino acids (Lysine, Arginine, Histidine) on the formation of total heterocyclic amines (HAs) was investigated in fried beef patties at 1% NaCl level. Different levels of basic amino acids (0.1%, 0.5%, 1%) significantly inhibited the formation of the total and individual HAs at 1% NaCl, and the inhibitory effect was more effective than 3% NaCl (6.19 ng/g, 26.93% inhibition) (P < 0.05). Lys at 1% reduced total HAs the most (2.46 ng/g, 70.88% inhibition), followed by 1% His (2.79 ng/g, 67.03% inhibition) and 1% Arg (3.43 ng/g, 59.51% inhibition). Compared to the 3% NaCl, the quality characteristics (moisture content, frying loss, texture profile, and color) of the fried beef patties were significantly improved when basic amino acids were added at 1% NaCl (P < 0.05). The lipid oxidation of fried beef patties was significantly inhibited by 1% Arg and 1% Lys at 1% NaCl level (P < 0.05). The results indicated that basic amino acids could inhibit the formation of total HAs while maintaining the quality of meat products at low NaCl condition.

Mapping recommendations towards an Asian Code Against Cancer (ACAC) as part of the World Code Against Cancer Framework: an Asian National Cancer Centers Alliance (ANCCA) initiative.

This paper outlines the process undertaken by Asian National Cancer Centers Alliance (ANCCA) members in working towards an Asian Code Against Cancer (ACAC). The process involves: (i) identification of the criteria for selecting the existing set of national recommendations for ACAC (ii) compilation of existing national codes or recommendations on cancer prevention (iii) reviewing the scientific evidence on cancer risk factors in Asia and (iv) establishment of one or more ACAC under the World Code Against Cancer Framework. A matrix of national codes or key recommendations against cancer in ANCCA member countries is presented. These include taking actions to prevent or control tobacco consumption, obesity, unhealthy diet, physical inactivity, alcohol consumption, exposure to occupational and environmental toxins; and to promote breastfeeding, vaccination against infectious agents and cancer screening. ANCCA will continue to serve as a supportive platform for collaboration, development, and advocacy of an ACAC jointly with the International Agency for Research on Cancer/World Health Organization (IARC/WHO).

Hydrogels containing KYNA promote angiogenesis and inhibit inflammation to improve the survival rate of multi-territory perforator flaps.

BACKGROUND: A new spray adhesive (KYNA-PF127) was established through the combination of thermosensitive hydrogel (Pluronic F127) and KYNA, aimed to investigate the effect of KYNA-PF127 on multi-territory perforator flaps and its possible molecular mechanism. MATERIALS AND METHODS: 36 SD male rats with 250-300 g were randomly divided into 3 groups (n = 12): control group, blank glue group and KYNA-PF127 group. KYNA-PF127 hydrogel was prepared and characterized for its morphology and properties using scanning electron microscopy. CCK-8 assay, scratch wound assay, transwell assay, tube formation assay and Ki67 staining were used to study the effect of KYNA-PF127 on the proliferation, migration, and tube formation of HUVECs. VEGF and FGF2 were measured by qPCR to evaluate the angiogenesis capacity of HUVECs in vitro. In vivo, the effect of each group on the survival area of the cross-zone perforator flap was evaluated, and angiogenesis was evaluated by HE and immunofluorescence (CD31 and MMP-9). The effect of inflammation on skin collagen fibers was assessed by Masson. Immunohistochemistry (SOD1, IL-1ß, TNF-α) was used to evaluate the effects of oxidative stress and inflammatory factors on multi-territory flaps. RESULTS: KYNA-PF127 has good sustained release and biocompatibility at 25% concentration. KYNA-PF127 promoted the proliferation, migration, and angiogenesis of HUVECs in vitro. In vivo, the survival area of multi-territory perforator flaps and angiogenic capability have increased after KYNA-PF127 intervention. KYNA-PF127 could effectively reduce the oxidative stress and inflammation of multi-territory perforator flaps. CONCLUSION: KYNA-PF127 promotes angiogenesis through its antioxidant stress and anti-inflammatory effects, and shows potential clinical value in promoting the survival viability and drug delivery of multi-territory perforator flaps.

Expansion and transmission dynamics of high risk carbapenem-resistant Klebsiella pneumoniae subclones in China: An epidemiological, spatial, genomic analysis.

AIMS: Carbapenem-resistant Klebsiella pneumonia (CRKP) is a global threat that varies by region. The global distribution, evolution, and clinical implications of the ST11 CRKP clone remain obscure. METHODS: We conducted a multicenter molecular epidemiological survey using isolates obtained from 28 provinces and municipalities across China between 2011 and 2021. We integrated sequences from public databases and performed genetic epidemiology analysis of ST11 CRKP. RESULTS: Among ST11 CRKP, KL64 serotypes exhibited considerable expansion, increasing from 1.54% to 46.08% between 2011 and 2021. Combining our data with public databases, the phylogenetic and phylogeography analyses indicated that ST11 CRKP appeared in the Americas in 1996 and spread worldwide, with key clones progressing from China's southeastern coast to the inland by 2010. Global phylogenetic analysis showed that ST11 KL64 CRKP has evolved to a virulent, resistant clade with notable regional spread. Single-nucleotide polymorphism (SNP) analysis identified BMPPS (bmr3, mltC, pyrB, ppsC, and sdaC) as a key marker for this clade. The BMPPS SNP clade is associated with high mortality and has strong anti-phagocytic and competitive traits in vitro. CONCLUSIONS: The high-risk ST11 KL64 CRKP subclone showed strong expansion potential and survival advantages, probably owing to genetic factors.

Natural Amino Acid-Bearing Carbamate Prodrugs of Daidzein Increase Water Solubility and Improve Phase II Metabolic Stability for Enhanced Oral Bioavailability.

Daidzein (DAN) is an isoflavone, and it is often found in its natural form in soybean and food supplements. DAN has poor bioavailability owing to its extremely low water solubility and first-pass metabolism. Herein, we hypothesized that a bioactivatable natural amino acid-bearing carbamate prodrug strategy could increase the water solubility and metabolic stability of DAN. To test our hypothesis, nine amino acid prodrugs of DAN were designed and synthesized. Compared with DAN, the optimal prodrug (daidzein-4'-O-CO-N-isoleucine, D-4'-I) demonstrated enhanced water solubility and improved phase II metabolic stability and activation to DAN in plasma. In addition, unlike the passive transport of DAN, D-4'-I maintained high permeability via organic anion-transporting polypeptide 2B1 (OATP2B1)-mediated transport. Importantly, D-4'-I increased the oral bioavailability by 15.5-fold, reduced the gender difference, and extended the linear absorption capacity in the pharmacokinetics of DAN in rats. Furthermore, D-4'-I exhibited dose-dependent protection against liver injury. Thus, the natural amino acid-bearing carbamate prodrug strategy shows potential in increasing water solubility and improving phase II metabolic stability to enhance the oral bioavailability of DAN.

Retagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.

AIM: To evaluate the efficacy and safety of retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin. MATERIALS AND METHODS: This multicentre, phase 3 trial consisted of a 16-week, randomized, double-blind, placebo-controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once-daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add-on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16. RESULTS: At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was -0.82% (95% CI, -1.05% to -0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2-hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported. CONCLUSIONS: Retagliptin 100 mg QD as an add-on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated.

Perioperative complications of minor and major reinterventions for peripheral arterial disease.

INTRODUCTION: Patients with peripheral arterial disease (PAD) frequently require reinterventions after lower-extremity revascularization (LER) to maintain perfusion. Current Society for Vascular Surgery guidelines define reinterventions as major or minor based on the magnitude of the procedure. While prior studies have compared primary LER procedures of different magnitudes, similar studies for reinterventions have not been performed. The objective of this study is to compare perioperative outcomes associated with major and minor reinterventions. METHODS: Patients undergoing LER for PAD at a tertiary care center from 2013 to 2017 were included. A retrospective review of electronic medical records was performed, and reinterventions were categorized as major or minor based on the procedure magnitude. Minor reinterventions included endovascular procedures and open revision with patch angioplasty, while major reinterventions were characterized by open surgical or endovascular LER with catheter-directed thrombolysis (CDT). Perioperative outcomes following LER were captured and compared for major and minor reinterventions. An additional subgroup analysis was performed comparing outcomes associated with major reinterventions stratified into open major surgical reinterventions and CDT. RESULTS: This study included 713 patients over a mean follow-up of 2.5 years. A total of 291 patients underwent 696 ipsilateral reinterventions (range = 1-12 reinterventions). Most reinterventions were minor (72.1%, N = 502) and 27.9% (N = 194) were major. Patients receiving reinterventions had an average age of 67.2 ± 11.5 and most were white (73.5%) males (60.1%) initially treated for claudication (58.2%) and CLTI (41.8%). There was significantly higher post-operative bleeding (9.8% vs 3.4%, p = .001), arterial thrombosis (3.1% vs 1.0%, p = .047), and acute renal failure (6.2% vs 2.4%, p = .014) after major reinterventions than minor. Additionally, major reinterventions had significantly higher return to the OR (17.0% vs 11.3%, p = .046) and longer hospital stays (7.5 vs 4.3 days, p = <.0001). Overall, major reinterventions were associated with significantly increased perioperative morbidity (37.6% vs 19.7%, p ≤ .001) with no difference in perioperative mortality. In the subgroup analysis, open reinterventions resulted in significantly longer hospital stays (8.6 days vs 5.5 days, p ≤ .001) and more wound infections than CDT (11.0% vs 0%, p = .017). However, there was no other significant difference in morbidity or mortality following treatment with open surgical reinterventions or CDT. CONCLUSIONS: In this study, major reinterventions after LER were associated with greater perioperative morbidity than minor reinterventions, with no difference in mortality. Major reinterventions performed via open surgery and CDT had similar morbidity and mortality.

Study on the mechanism of action of methane production by co-fermentation of sludge and lignite.

To improve the methanogenic efficiency of lignite anaerobic fermentation and explore innovative approaches to sludge utilization, a co-fermentation technique involving lignite and sludge was employed for converting biomass into biomethane. Volatile suspended solids were introduced as a native enrichment of the sludge and mixed with lignite for fermentation. The synergistic fermentation mechanism between sludge and lignite for biomethane production was analyzed through biochemical methane potential experiments, measurement of various parameters pre- and post-fermentation, observation of bacterial population changes during the peak of reaction, carbon migration assessment, and evaluation of rheological characteristics. The results showed that the addition of sludge in the anaerobic fermentation process improved the microorganisms' ability to degrade lignite and bolstered biomethane production. Notably, the maximum methane production recorded was 215.52 mL/g-volatile suspended solids, achieved at a sludge to coal ratio of 3:1, with a synergistic growth rate of 25.37%. Furthermore, the removal rates of total suspended solids, and total chemical oxygen demand exhibited an upward trend with an increasing percentage of sludge in the mixture. The relative abundance and activity of the methanogens population were found to increase with an appropriate ratio of sludge to lignite. This observation confirmed the migration of carbon between the solid-liquid-gas phases, promoting enhanced system affinity. Additionally, the changes in solid-liquid phase parameters before and after the reaction indicated that the addition of sludge improved the system's degradation capacity. The results of the study hold significant implications in realizing the resource utilization of sludge and lignite while contributing to environmental protection endeavors.

Characterization of a pangolin SARS-CoV-2-related virus isolate that uses the human ACE2 receptor.

Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins, showing a potential threat to humans. Here we report the infectivity and pathogenicity of the SARS-CoV-2-related virus, PCoV-GX/P2V, which was isolated from a Malayan pangolin (Manis javanica). PCoV-GX/P2V could grow in human hepatoma, colorectal adenocarcinoma cells, and human primary nasal epithelial cells. It replicated more efficiently in cells expressing human angiotensin-converting enzyme 2 (hACE2) as SARS-CoV-2 did. After intranasal inoculation to the hACE2-transgenic mice, PCoV-GX/P2V not only replicated in nasal turbinate and lungs, but also caused interstitial pneumonia, characterized by infiltration of mixed inflammatory cells and multifocal alveolar hemorrhage. Existing population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V infection. These findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.

Neoadjuvant chemoimmunotherapy for locally advanced esophageal squamous cell carcinoma: Data from literature review and a real-world analysis.

BACKGROUND: Neoadjuvant chemoimmunotherapy (NCIT) for locally advanced esophageal squamous cell carcinoma (ESCC) is supported by increasing data, but the sample size is limited, and the findings are not completely consistent. We conducted a real-world study and a meta-analysis to evaluate the efficacy and safety of NCIT in locally advanced ESCC. METHODS: We retrospectively assessed the outcomes of patients with locally advanced ESCC who completed NICT and subsequent esophagectomy at our hospital between January 2019 and December 2022, including pathological complete response (pCR) rate, major pathological response (MPR) rate, 1-, 2-, and 3-year overall survival (OS) rates, disease control rate (DCR), objective response rate (ORR), 1-year recurrence rate, R0 resection rate and adverse events. Moreover, a meta-analysis of 27 published literatures was also conducted for comparison. RESULTS: In the analysis, 128 patients were studied, with 25% achieving pCR, 46.1% MPR, and 99.2% R0 resection. The 1-, 2-, and 3-year OS rates were 91.41% (95% CI: 85.15%-95.63%), 75.00% (95% CI: 66.58%-82.23%) and 64.84% (95% CI: 55.91%-73.07%).ORR and DCR were 31.2% (95% CI: 23.31-39.99) and 64.1% (95% CI: 55.15%-72.38%), and the 1-year recurrence rate was 26.7% (95% CI: 22.5%-38.1%). Treatment-related events occurred in 96.1% but were acceptable. In a meta-analysis of 27 studies with 1734 patients, pooled rates for pCR, MPR, ORR, DCR, and R0 resection were 29%, 52%, 71%, 97%, and 98%, respectively, with a 1-year recurrence rate of 12%. CONCLUSION: NCIT is safe and provides potential survival benefits for patients with locally advanced ESCC. However, randomized phase 3 trial data is still needed.

Organochlorine pesticides and risk of papillary thyroid cancer in U.S. military personnel: a nested case-control study.

BACKGROUND: The effects of organochlorine pesticide (OCP) exposure on the development of human papillary thyroid cancer (PTC) are not well understood. A nested case-control study was conducted with data from the U.S. Department of Defense Serum Repository (DoDSR) cohort between 2000 and 2013 to assess associations of individual OCPs serum concentrations with PTC risk. METHODS: This study included 742 histologically confirmed PTC cases (341 females, 401 males) and 742 individually-matched controls with pre-diagnostic serum samples selected from the DoDSR. Associations between categories of lipid-corrected serum concentrations of seven OCPs and PTC risk were evaluated for classical PTC and follicular PTC using conditional logistic regression, adjusted for body mass index category and military branch to compute odds ratios (OR) and 95% confidence intervals (CIs). Effect modification by sex, birth cohort, and race was examined. RESULTS: There was no evidence of associations between most of the OCPs and PTC, overall or stratified by histological subtype. Overall, there was no evidence of an association between hexachlorobenzene (HCB) and PTC, but stratified by histological subtype HCB was associated with significantly increased risk of classical PTC (third tertile above the limit of detection (LOD) vs.