Contribution of FOS in neutrophils to venous thromboembolism via miR-144 based on bioinformatic prediction and validation.

The Finkel-Biskis-Jinkins Osteosarcoma (c-Fos; encoded by FOS) plays an important role in several cardiovascular diseases, including atherosclerosis and stroke. However, the relationship between FOS and venous thromboembolism (VTE) remains unknown. We identified differentially expressed genes in Gene Expression Omnibus dataset, GSE48000, comprising VTE patients and healthy individuals, and analysed them using CIBERSORT and weighted co-expression network analysis (WGCNA). FOS and CD46 expressions were significantly downregulated (FOS p = 2.26E-05, CD64 p = 8.83E-05) and strongly linked to neutrophil activity in VTE. We used GSE19151 and performed PCR to confirm that FOS and CD46 had diagnostic potential for VTE; however, only FOS showed differential expression by PCR and ELISA in whole blood samples. Moreover, we found that hsa-miR-144 which regulates FOS expression was significantly upregulated in VTE. Furthermore, FOS expression was significantly downregulated in neutrophils of VTE patients (p = 0.03). RNA sequencing performed on whole blood samples of VTE patients showed that FOS exerted its effects in VTE via the leptin-mediated adipokine signalling pathway. Our results suggest that FOS and related genes or proteins can outperform traditional clinical markers and may be used as diagnostic biomarkers for VTE.

Integrated chromosomal instability and tumor microbiome redefined prognosis-related subtypes of pancreatic cancer.

BACKGROUND: Pancreatic cancer is a common malignancy with poor prognosis and limited treatment. Here we aimed to investigate the role of host chromosomal instability (CIN) and tumor microbiome in the prognosis of pancreatic cancer patients. METHODS: One hundred formalin-fixed paraffin-embedded (FFPE) pancreatic cancer samples were collected. DNA extracted from FFPE samples were analyzed by low-coverage whole-genome sequencing (WGS) via a customized bioinformatics workflow named ultrasensitive chromosomal aneuploidy detector. RESULTS: Samples are tested according to the procedure of ultrasensitive chromosomal aneuploidy detector (UCAD). We excluded 2 samples with failed quality control, 1 patient lost to follow-up and 6 dead in the perioperative period. The final 91 patients were admitted for the following analyses. Thirteen (14.3%) patients with higher CIN score had worse overall survival (OS) than those with lower CIN score. The top 20 microbes in pancreatic cancer samples included 15 species of bacteria and 5 species of viruses. Patients with high human herpesvirus (HHV)-7 and HHV-5 DNA reads exhibited worse OS. Furthermore, we classified 91 patients into 3 subtypes. Patients with higher CIN score (n =13) had the worst prognosis (median OS 6.9 mon); patients with lower CIN score but with HHV-7/5 DNA load (n = 24) had worse prognosis (median OS 10.6 mon); while patients with lower CIN score and HHV-7/5 DNA negative (n = 54) had the best prognosis (median OS 21.1 mon). CONCLUSIONS: High CIN and HHV-7/5 DNA load were associated with worse survival of pancreatic cancer. The novel molecular subtypes of pancreatic cancer based on CIN and microbiome had prognostic value.

EcoDetect-YOLO: A Lightweight, High-Generalization Methodology for Real-Time Detection of Domestic Waste Exposure in Intricate Environmental Landscapes.

In response to the challenges of accurate identification and localization of garbage in intricate urban street environments, this paper proposes EcoDetect-YOLO, a garbage exposure detection algorithm based on the YOLOv5s framework, utilizing an intricate environment waste exposure detection dataset constructed in this study. Initially, a convolutional block attention module (CBAM) is integrated between the second level of the feature pyramid etwork (P2) and the third level of the feature pyramid network (P3) layers to optimize the extraction of relevant garbage features while mitigating background noise. Subsequently, a P2 small-target detection head enhances the model's efficacy in identifying small garbage targets. Lastly, a bidirectional feature pyramid network (BiFPN) is introduced to strengthen the model's capability for deep feature fusion. Experimental results demonstrate EcoDetect-YOLO's adaptability to urban environments and its superior small-target detection capabilities, effectively recognizing nine types of garbage, such as paper and plastic trash. Compared to the baseline YOLOv5s model, EcoDetect-YOLO achieved a 4.7% increase in mAP0.5, reaching 58.1%, with a compact model size of 15.7 MB and an FPS of 39.36. Notably, even in the presence of strong noise, the model maintained a mAP0.5 exceeding 50%, underscoring its robustness. In summary, EcoDetect-YOLO, as proposed in this paper, boasts high precision, efficiency, and compactness, rendering it suitable for deployment on mobile devices for real-time detection and management of urban garbage exposure, thereby advancing urban automation governance and digital economic development.

The role of macrophage TAM receptor family in the acute-to-chronic progression of liver disease: From friend to foe?

Hepatic macrophages, the key cellular components of the liver, emerge as essential players in liver inflammation, tissue repair and subsequent fibrosis, as well as tumorigenesis. Recently, the TAM receptor tyrosine kinase family, consisting of Tyro3, Axl and MerTK, was found to be a pivotal modulator of macrophages. Activation of macrophage TAM receptor signalling promotes the efferocytosis of apoptotic cells and skews the polarization of macrophages. After briefly reviewing the mechanisms of TAM receptor signalling in macrophage polarization, we focus on their role in liver diseases from acute injury to chronic inflammation, fibrosis and then to tumorigenesis. Notably, macrophage TAM receptor signalling seems to be a two-edged sword for liver diseases. On one hand, the activation of TAM receptor signalling inhibits inflammation and facilitates tissue repair during acute liver injury. On the other hand, continuous activation of the signalling contributes to the process of chronic inflammation into fibrosis and tumorigenesis by evoking hepatic stellate cells and inhibiting anti-tumour immunity. Therefore, targeting macrophage TAM receptors and clarifying its downstream pathways will be exciting prospects for the precaution and treatment of liver diseases, particularly at different stages or statuses.

cGAS and cancer therapy: a double-edged sword.

Cyclic guanosine monophosphate-adenosine monophosphate adenosine synthetase (cGAS) is a DNA sensor that detects and binds to cytosolic DNA to generate cyclic GMP-AMP (cGAMP). As a second messenger, cGAMP mainly activates the adapter protein STING, which induces the production of type I interferons (IFNs) and inflammatory cytokines. Mounting evidence shows that cGAS is extensively involved in the innate immune response, senescence, and tumor immunity, thereby exhibiting a tumor-suppressive function, most of which is mediated by the STING pathway. In contrast, cGAS can also act as an oncogenic factor, mostly by increasing genomic instability through inhibitory effects on DNA repair, suggesting its utility as an antitumor target. This article reviews the roles and the underlying mechanisms of cGAS in cancer, particularly focusing on its dual roles in carcinogenesis and tumor progression, which are probably attributable to its classical and nonclassical functions, as well as approaches targeting cGAS for cancer therapy.

Comparative genomic analysis of head and body/tail of pancreatic ductal adenocarcinoma at early and late stages.

Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers, can be divided into head and body/tail cancers anatomically. We previously reported a prognostic relevance of tumour location in resectable PDAC. This study aimed to further explore the mechanism underlying the molecular diversity between the head and body/tail of PDACs. We detected tumour genomes in 154 resectable (surgery) and non-resectable (biopsy) PDACs using a next-generation sequencing panel. Wilcoxon's rank test or Fisher's exact test was used for evaluating associations between clinical characteristics, mutation frequency and survival probability between the two cohorts. Compared with pancreatic head cancers, pancreatic body/tail cancers showed significantly more enriched genomic alterations in KRAS (97.1% vs 82.4%, P = 0.004) and SMAD4 (42.0% vs 21.2%, P = 0.008). At early stages (I-II), the SMAD4 mutation rate was significantly higher in pancreatic body/tail cancers than pancreatic head cancers (56.0% vs 26.5%, P = 0.021). At late stages (III-IV), pancreatic body/tail cancers presented significantly higher KRAS mutation rate (100.0% vs 75.8%, P = 0.001), higher frequency of MAPK pathway mutation (100% vs 87.8%, P = 0.040) and lower rates of druggable genomic alterations (30.8% vs 57.6%, P = 0.030) than pancreatic head cancers. Our work points out that pancreatic body/tail cancer seems to be more malignant than pancreatic head cancer at late stages.

An integrated proteomics and metabolomics approach to assess graft quality and predict early allograft dysfunction after liver transplantation: a retrospective cohort study.

BACKGROUND: Early allograft dysfunction (EAD) is a common complication after liver transplantation (LT) and is associated with poor prognosis. Graft itself plays a major role in the development of EAD. We aimed to reveal the EAD-specific molecular profiles to assess graft quality and establish EAD predictive models. METHODS: A total of 223 patients who underwent LT were enrolled and divided into training ( n =73) and validation ( n =150) sets. In the training set, proteomics was performed on graft biopsies, together with metabolomics on paired perfusates. Differential expression, enrichment analysis, and protein-protein interaction network were used to identify the key molecules and pathways involved. EAD predictive models were constructed using machine learning and verified in the validation set. RESULTS: A total of 335 proteins were differentially expressed between the EAD and non-EAD groups. These proteins were significantly enriched in triglyceride and glycerophospholipid metabolism, neutrophil degranulation, and the MET-related signaling pathway. The top 12 graft proteins involved in the aforementioned processes were identified, including GPAT1, LPIN3, TGFB1, CD59, and SOS1. Moreover, downstream metabolic products, such as lactate dehydrogenase, interleukin-8, triglycerides, and the phosphatidylcholine/phosphorylethanolamine ratio in the paired perfusate displayed a close relationship with the graft proteins. To predict the occurrence of EAD, an integrated model using perfusate metabolic products and clinical parameters showed areas under the curve of 0.915 and 0.833 for the training and validation sets, respectively. It displayed superior predictive efficacy than that of currently existing models, including donor risk index and D-MELD scores. CONCLUSIONS: We identified novel biomarkers in both grafts and perfusates that could be used to assess graft quality and provide new insights into the etiology of EAD. Herein, we also offer a valid tool for the early prediction of EAD.

Low-condensation diesel use contributes to winter haze in cold regions of China.

The application of low-condensation diesel in cold regions with extremely low ambient temperatures (-14 to -29 °C) has enabled the operation of diesel vehicles. Still, it may contribute to heavy haze pollution in cold regions during winter. Here we examine pollutant emissions from low-condensation diesel in China. We measure the emissions of elemental carbon (EC), organic carbon (OC), and elements, including heavy metals such as arsenic (As). Our results show that low-condensation diesel increased EC and OC emissions by 2.5 and 2.6 times compared to normal diesel fuel, respectively. Indicators of vehicular sources, including EC, As, lead (Pb), cadmium (Cd), chromium (Cr), nickel (Ni), and manganese (Mn), increased by approximately 20.2-162.5% when using low-condensation diesel. Seasonal variation of vehicular source indicators, observed at road site ambient environments revealed the enhancement of PM2.5 pollution by the application of low-condensation diesel in winter. These findings suggest that -35# diesel, a low-cetane index diesel, may enhance air pollution in winter, according to a dynamometer test conducted in laboratory. It raises questions about whether higher emissions are released if -35# diesel is applied to running vehicles in real-world cold ambient environments.

Molecular epidemiology and phylogenetic analysis of influenza viruses A (H3N2) and B/Victoria during the COVID-19 pandemic in Guangdong, China.

BACKGROUND: Non-pharmaceutical measures and travel restrictions have halted the spread of coronavirus disease 2019 (COVID-19) and influenza. Nonetheless, with COVID-19 restrictions lifted, an unanticipated outbreak of the influenza B/Victoria virus in late 2021 and another influenza H3N2 outbreak in mid-2022 occurred in Guangdong, southern China. The mechanism underlying this phenomenon remains unknown. To better prepare for potential influenza outbreaks during COVID-19 pandemic, we studied the molecular epidemiology and phylogenetics of influenza A(H3N2) and B/Victoria that circulated during the COVID-19 pandemic in this region. METHODS: From January 1, 2018 to December 31, 2022, we collected throat swabs from 173,401 patients in Guangdong who had acute respiratory tract infections. Influenza viruses in the samples were tested using reverse transcription-polymerase chain reaction, followed by subtype identification and sequencing of hemagglutinin (HA) and neuraminidase (NA) genes. Phylogenetic and genetic diversity analyses were performed on both genes from 403 samples. A rigorous molecular clock was aligned with the phylogenetic tree to measure the rate of viral evolution and the root-to-tip distance within strains in different years was assessed using regression curve models to determine the correlation. RESULTS: During the early period of COVID-19 control, various influenza viruses were nearly undetectable in respiratory specimens. When control measures were relaxed in January 2020, the influenza infection rate peaked at 4.94% (39/789) in December 2021, with the influenza B/Victoria accounting for 87.18% (34/39) of the total influenza cases. Six months later, the influenza infection rate again increased and peaked at 11.34% (255/2248) in June 2022; influenza A/H3N2 accounted for 94.51% (241/255) of the total influenza cases in autumn 2022. The diverse geographic distribution of HA genes of B/Victoria and A/H3N2 had drastically reduced, and most strains originated from China. The rate of B/Victoria HA evolution (3.11 × 10-3, P < 0.05) was 1.7 times faster than before the COVID-19 outbreak (1.80 × 10-3, P < 0.05). Likewise, the H3N2 HA gene's evolution rate was 7.96 × 10-3 (P < 0.05), which is 2.1 times faster than the strains' pre-COVID-19 evolution rate (3.81 × 10-3, P < 0.05). CONCLUSIONS: Despite the extraordinarily low detection rate of influenza infection, concealed influenza transmission may occur between individuals during strict COVID-19 control. This ultimately leads to the accumulation of viral mutations and accelerated evolution of H3N2 and B/Victoria viruses. Monitoring the evolution of influenza may provide insights and alerts regarding potential epidemics in the future.

Hidden pathogen risk in mature compost: Low optimal growth temperature confers pathogen survival and activity during manure composting.

Livestock manure is a major reservoir for pathogens, posing significant environmental risks if used untreated. The efficacy of composting in fully inactivating pathogens remains controversial, particularly regarding the influence of their optimal growth temperature (OGT). This study investigated the composition and dynamic changes of pathogen communities and virulence factors (VFs) during the composting of chicken, bovine, ovine, and swine manure. We identified 134 pathogens across 16 composting piles, with ten pathogens exhibited increased abundance and transcriptional activity in curing phase. They included high-risk VFs-carrying pathogens, such as Mycolicibacterium thermoresistibile and Mycolicibacterium phlei, indicating the hidden pathogen risk in mature compost. Community-scale analyses revealed a linkage of these pathogens' survival with their low OGT and an increased number of heat shock proteins (HSPs), enabling them to tolerate high temperatures and regrow. Integrating our data with prior composting studies, we found that the surviving pathogens express 42 VFs and their persistence in mature compost was a widespread issue, highlighting a greater risk of pathogen spread than previously thought. Finally, we compiled the 134 pathogens and 1009 VFs into a comprehensive Environmental Risk of Compost Pathogens (ERCP) catalog, providing a valuable resource for routine pathogen surveillance.

Cross-talk of alpha tocopherol-associated protein and JNK controls the oxidative stress-induced apoptosis in prostate cancer cells.

Excess intracellular reactive oxygen species (ROS) beyond a threshold can induce apoptosis in cancer cells. However, the signal pathways that can augment the proapoptotic function of ROS remain largely unknown. We previously identified a tumor suppressor, alpha-tocopherol-associated protein (TAP), yet little is known regarding the role of TAP in the apoptotic signaling in prostate cancer. Interestingly, we recently found that exposure of prostate cancer cells to hydrogen peroxide (H(2)O(2) ) resulted in induced apoptosis as well as increased expression of TAP. Small interfering RNA (siRNA) mediated silencing of endogenous TAP expression conferred effective protection from H(2)O(2) -induced apoptosis. Further mechanistic study showed exposure of prostate cancer cells to H(2)O(2) resulted in increased phosphorylation of both JNK and c-Jun, and TAP siRNA effectively decreased H(2)O(2) -induced JNK and c-Jun phosphorylation. Immunoprecipitation experiments revealed that JNK physically associates with TAP. Furthermore, signaling downstream of JNK to the AP-1 complex and BH-3-only subfamily were found to be regulated on changing the TAP expression status. TAP could also promote the oxidative stress-induced apoptosis effect of docetaxel. In the mice xenograft model, H(2)O(2) treatment induced TAP expression, JNK phosphorylation and apoptosis of prostate cancer. Recombinant adeno-associated virus 2 (rAAV2)-TAP injection significantly sensitizes this H(2)O(2) proapoptotic effect. Together, we have identified a novel functional mechanism that the cross-talk of TAP-JNK is involved in oxidative stress-induced apoptosis in prostate cancer cells. Disrupting the redox balance of cancer cells by this signaling may enable therapeutic selectivity and provide benefit to overcome the drug resistance of prostate cancer.

Immunotherapy for hepatocellular carcinoma recurrence after liver transplantation, can we harness the power of immune checkpoint inhibitors?

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death globally and liver transplantation (LT) can serve as the best curative treatment option. However, HCC recurrence after LT remains the major obstacle to the long-term survival of recipients. Recently, immune checkpoint inhibitors (ICIs) have revolutionized the treatment of many cancers and provided a new treatment strategy for post-LT HCC recurrence. Evidence has been accumulated with the real-world application of ICIs in patients with post-LT HCC recurrence. Notably, the use of these agents as immunity boosters in recipients treated with immunosuppressors is still controversial. In this review, we summarized the immunotherapy for post-LT HCC recurrence and conducted an efficacy and safety evaluation based on the current experience of ICIs for post-LT HCC recurrence. In addition, we further discussed the potential mechanism of ICIs and immunosuppressive agents in regulating the balance between immune immunosuppression and lasting anti-tumor immunity.

Empirical assessment of carbon emissions in Guangdong Province within the framework of carbon peaking and carbon neutrality: a lasso-TPE-BP neural network approach.

The escalating global greenhouse gas emission crisis necessitates a robust scientific carbon accounting framework and innovative development approaches. Achieving emission peaks remains the primary goal for emission reduction. Guangdong Province, a pivotal region in China, faces pressure to reduce carbon emissions. In this study, data was leveraged from the China Carbon Accounting Database (CEADS) and panel data from the "Guangdong Statistical Yearbook" spanning 1997 to 2022. Factors impacting carbon emissions were selected based on Guangdong Province's carbon reduction goals, macroeconomic development strategies, and economic-population dynamics. To address multicollinearity, lasso regression identified key factors, including population size, economic development level, energy intensity, and technology factors. A novel STIRPAT extended model, combined with the BP neural network optimized using the TPE algorithm, enhanced carbon emission predictions for Guangdong Province. Employing scenario analysis, five scenarios were generated in alignment with the planning policies of Guangdong Province, to forecast carbon emissions from 2020 to 2050. The results suggest that to achieve a win-win situation for both economic development and environmental protection, Guangdong Province should prioritize the energy-saving scenario (S2), which aligns with the "13th Five-Year Plan's" ecological and green development directives, to reach a projected carbon peak of 637.05Mt by 2030. In conclusion, recommendations for carbon reduction are proposed in the areas of low-carbon transformation for the population, sustainable economic development, and the development of low-carbon technologies.

Phylogenetic and ecophysiological novelty of subsurface mercury methylators in mangrove sediments.

Mangrove sediment is a crucial component in the global mercury (Hg) cycling and acts as a hotspot for methylmercury (MeHg) production. Early evidence has documented the ubiquity of well-studied Hg methylators in mangrove superficial sediments; however, their diversity and metabolic adaptation in the more anoxic and highly reduced subsurface sediments are lacking. Through MeHg biogeochemical assay and metagenomic sequencing, we found that mangrove subsurface sediments (20-100 cm) showed a less hgcA gene abundance but higher diversity of Hg methylators than superficial sediments (0-20 cm). Regional-scale investigation of mangrove subsurface sediments spanning over 1500 km demonstrated a prevalence and family-level novelty of Hg-methylating microbial lineages (i.e., those affiliated to Anaerolineae, Phycisphaerae, and Desulfobacterales). We proposed the candidate phylum Zixibacteria lineage with sulfate-reducing capacity as a currently understudied Hg methylator across anoxic environments. Unlike other Hg methylators, the Zixibacteria lineage does not use the Wood-Ljungdahl pathway but has unique capabilities of performing methionine synthesis to donate methyl groups. The absence of cobalamin biosynthesis pathway suggests that this Hg-methylating lineage may depend on its syntrophic partners (i.e., Syntrophobacterales members) for energy in subsurface sediments. Our results expand the diversity of subsurface Hg methylators and uncover their unique ecophysiological adaptations in mangrove sediments.

Assessing Donor Liver Quality and Restoring Graft Function in the Era of Extended Criteria Donors.

Liver transplantation (LT) is the final treatment option for patients with end-stage liver disease. The increasing donor shortage results in the wide usage of grafts from extended criteria donors across the world. Using such grafts is associated with the elevated incidences of post-transplant complications including initial nonfunction and ischemic biliary tract diseases, which significantly reduce recipient survival. Although several clinical factors have been demonstrated to impact donor liver quality, accurate, comprehensive, and effective assessment systems to guide decision-making for organ usage, restoration or discard are lacking. In addition, the development of biochemical technologies and bioinformatic analysis in recent years helps us better understand graft injury during the perioperative period and find potential ways to restore graft function. Moreover, such advances reveal the molecular profiles of grafts or perfusate that are susceptible to poor graft function and provide insight into finding novel biomarkers for graft quality assessment. Focusing on donors and grafts, we updated potential biomarkers in donor blood, liver tissue, or perfusates that predict graft quality following LT, and summarized strategies for restoring graft function in the era of extended criteria donors. In this review, we also discuss the advantages and drawbacks of these potential biomarkers and offer suggestions for future research.

Sarsasapogenin inhibits YAP1-dependent chondrocyte ferroptosis to alleviate osteoarthritis.

The involvement of chondrocyte ferroptosis in the development of osteoarthritis (OA) has been observed, and Sarsasapogenin (Sar) has therapeutic promise in a variety of inflammatory diseases. This study investigates the potential influence of Sar on the mechanism of chondrocyte ferroptotic cell death in the progression of osteoarthritic cartilage degradation. An in vivo medial meniscus destabilization (DMM)-induced OA animal model as well as an in vitro examination of chondrocytes in an OA microenvironment induced by interleukin-1ß (IL-1ß) exposure were employed. Histology, immunofluorescence, quantitative RT-PCR, Western blot, cell viability, and Micro-CT analysis were utilized in conjunction with gene overexpression and knockdown to evaluate the chondroprotective effects of Sar in OA progression and the role of Yes-associated protein 1 (YAP1) in Sar-induced ferroptosis resistance of chondrocytes. In this study we found Sar reduced chondrocyte ferroptosis and OA progression. And Sar-induced chondrocyte ferroptosis resistance was mediated by YAP1. Furthermore, infection of siRNA specific to YAP1 in chondrocytes reduced Sar's chondroprotective and ferroptosis-suppressing effects during OA development. The findings suggest that Sar mitigates the progression of osteoarthritis by decreasing the sensitivity of chondrocytes to ferroptosis through the promotion of YAP1, indicating that Sar has the potential to serve as a therapeutic approach for diseases associated with ferroptosis.

Decoding Single-cell Landscape and Intercellular Crosstalk in the Transplanted Liver.

BACKGROUND: Liver transplantation (LT) is the most effective treatment for various end-stage liver diseases. However, the cellular complexity and intercellular crosstalk of the transplanted liver have constrained analyses of graft reconstruction after LT. METHODS: We established an immune-tolerated orthotopic LT mouse model to understand the physiological process of graft recovery and intercellular crosstalk. We employed single-cell RNA sequencing and cytometry by time-of-flight to comprehensively reveal the cellular landscape. RESULTS: We identified an acute and stable phase during perioperative graft recovery. Using single-cell technology, we made detailed annotations of the cellular landscape of the transplanted liver and determined dynamic modifications of these cells during LT. We found that 96% of graft-derived immune cells were replaced by recipient-derived cells from the preoperative to the stable phase. However, CD206 + MerTK + macrophages and CD49a + CD49b - natural killer cells were composed of both graft and recipient sources even in the stable phase. Intriguingly, the transcriptional profiles of these populations exhibited tissue-resident characteristics, suggesting that recipient-derived macrophages and natural killer cells have the potential to differentiate into 'tissue-resident cells' after LT. Furthermore, we described the transcriptional characteristics of these populations and implicated their role in regulating the metabolic and immune remodeling of the transplanted liver. CONCLUSIONS: In summary, this study delineated a cell atlas (type-proportion-source-time) of the transplanted liver and shed light on the physiological process of graft reconstruction and graft-recipient crosstalk.

Temporary impact on medical system and effectiveness of mitigation strategies after COVID-19 policy adjustment in China: a modeling study.

Background: As China amends its "zero COVID" strategy, a sudden increase in the number of infections may overwhelm medical resources and its impact has not been quantified. Specific mitigation strategies are needed to minimize disruption to the healthcare system and to prepare for the next possible epidemic in advance. Method: We develop a stochastic compartmental model to project the burden on the medical system (that is, the number of fever clinic visits and admission beds) of China after adjustment to COVID-19 policy, which considers the epidemiological characteristics of the Omicron variant, age composition of the population, and vaccine effectiveness against infection and severe COVD-19. We also estimate the effect of four-dose vaccinations (heterologous and homologous), antipyretic drug supply, non-pharmacological interventions (NPIs), and triage treatment on mitigating the domestic infection peak. Result: As to the impact on the medical system, this epidemic is projected to result in 398.02 million fever clinic visits and 16.58 million hospitalizations, and the disruption period on the healthcare system is 18 and 30 days, respectively. Antipyretic drug supply and booster vaccination could reduce the burden on emergency visits and hospitalization, respectively, while neither of them could not reduce to the current capacity. The synergy of several different strategies suggests that increasing the heterologous booster vaccination rate for older adult to over 90% is a key measure to alleviate the bed burden for respiratory diseases on the basis of expanded healthcare resource allocation. Conclusion: The Omicron epidemic followed the adjustment to COVID-19 policy overloading many local health systems across the country at the end of 2022. The combined effect of vaccination, antipyretic drug supply, triage treatment, and PHSMs could prevent overwhelming medical resources.

A practical pressure measuring method for the upper urinary tract during ureteroscopy.

PURPOSE: The purpose of this study was to develop and test a method for measuring pressure in the upper urinary tract during ureteroscopic operations and to evaluate its efficacy and clinical significance. METHODS: A total of 44 patients, each with a ureteral calculus in the proximal ureteral segment, were enrolled in the study group: 21 patients with an acute and 23 with a chronic obstruction. The ureteroscope was passed forward to the upper segment of the obstructed ureter immediately after the calculus was broken and the intraluminal ureteral pressure was then transmitted along with the irrigant flow (0.9% sodium chloride). RESULTS: The mean ureteral pressures of the acute obstruction subgroup, the chronic obstruction subgroup and the control group were 74.5 mmHg (22-180 mmHg), 32.5 mmHg (9-53 mmHg) and 10.2 mmHg (8-13 mmHg), respectively. A significant correlation was found between ureteral pressure and the following indexes: the duration of the obstruction (r=0.985), the diameter of the ureter above the calculus (r=0.878) and the depth of the hydronephrosis of the renal pelvis (r=0.862). No associations were observed between the pressure and the serum creatinine level (r=0.214) or the urinary leukocyte count (r=0.047). The intraluminal pressure correlated with the glomerular flow rate (GFR) of the affected kidney (r =0.975, P =0.001). CONCLUSIONS: This new method is non-invasive, practical and reproducible. Measuring the intraluminal pressure of the ureter can provide a valuable index to quantify the severity of the obstruction of the upper urinary tract, which is helpful for the prediction of the affected renal function prognosis.

The Pharmacological Mechanisms of Xiaochaihutang in Treating Breast Cancer Based on Network Pharmacology.

Background: As a classic prescription in Chinese medicine treatment, Xiaochaihutang (XCHT) can improve the clinical effect and reduce serum tumor markers in patients with breast cancer (BC). However, there has not been any study to confirm the mechanism. We used bioinformatics analysis and network pharmacology to find the potential targets. Methods: The differentially expressed genes (DEGs) of BC were identified from the Cancer Genome Atlas (TCGA) dataset. Then, we utilized weighted coexpression network analysis (WGCNA) with the same dataset. The target genes of BC were obtained by comparing genes of DEGs and in significant modules of WGCNA. Drug targets of XCHT from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database were intersected with the targets of BC. The protein-protein interaction (PPI) of the drug targets was analysed by using the STRING database. We utilized the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analysis (KEGG) enrichment analysis to identify the specific pathways and key target proteins. Receiver operator characteristic (ROC) curve was used as the verification of drug targets. Molecular docking was performed to visualize the patterns of interactions between the effective molecule and targeted protein. Results: We obtained a set of 21 target genes, which mainly encode neurotransmitter receptors or related transporters, such as OPRD1, 5-HT2A, and so on. In addition, enrichment analyses of 21 target genes showed that they were mainly concentrated in pathways related to the nervous system. Molecular docking was performed on the target gene of BC. Six active compounds can enter the active pocket of target gene, namely, naringenin, beta-sitosterol, coumestrol, nuciferine, beta-sitosterol, and protopine, thereby exerting potential therapeutic effects in BC. Conclusions: Our analysis shows that the mechanism of XCHT in the treatment of BC is mainly acting on the neurogenesis in the microenvironment of breast tumor tissue.