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Abstract The aim of this retrospective study was to evaluate the efficiency and safety of total body irradiation plus cyclophosphamide (TBI/Cy) followed by autogenetic hematopoietic stem cell transplantation (auto-HSCT) in T-LBL/ALL patients that cannot receive allogeneic hematopoietic stem cell transplant (allo-HSCT). Between 2013 and 2023, 24 patients received auto-HSCT following by TBI/Cy, 26 patients underwent allo-HSCT, all patients achieved completed hematopoietic reconstitution after HSCT. The progression free survival (PFS) and overall survival (OS) had no statistically significant differences between the two groups (P = 0.791, HR 1.127, 95%CI 0.456–2.785; P = 0.456, HR 0.685, 95%CI 0.256–1.828). Although the cumulative incidence of relapse was lower for patients who received allo-HSCT than auto-HSCT (P = 0.033, HR 3.707, 95%CI 1.188–11.570, 2-year relapse 11.5% vs. 33.3%), the incidence of non-relapse mortality (NRM) was higher than that in the auto-HSCT group (P = 0.014, HR 0.000, 95%CI -1.000 - -1.000, 2-year NRM, 23.1% vs. 0%). Trough Landmark analysis, the two groups showed a statistically significant difference in 3-year PFS and 4-year OS curves (Figure S2A&B, P = 0.039, HR 0.426, 95%CI 0.163–1.117; P = 0.014, HR 0.317, 95%CI 0.113–0.887). By COX analysis, poor baseline performance status (ECOG-PS ≥ 2) and CNS involvement were risk factors for PFS and OS. In conclusion, TBI/Cy followed by auto-HSCT is a good choice next to allo-HSCT for patients with T-LBL/ALL.

Abstract Background Aims of this study were to compare the functional and radiographic results, perioperative complication after lateral unicompartmental knee arthroplasty (LUKA) with total knee arthroplasty (TKA) and the legacy constrained condylar knee (LCCK) arthroplasty for the treatment of lateral compartmental knee osteoarthritis (LCKOA), and to provide a basis for the treatment of LCKOA. Methods From January 2021 to January 2024, analyzed retrospectively clinical data of 74 patients with LCKOA treated with LUKA, TKA and LCCK arthroplasty. According to the operation plan, the patients were divided into three groups: LUKA group (23 cases), TKA group (23 cases) and LCCK group (28 cases). The changes of hip-knee-ankle (HKA) angle of the affected knee before and after operation were measured. All patients were assessed using the operation time, blood loss during operation, incision length, visual analogue scale (VAS) score before operation and after operation, Hospital for Special Surgery score (HSS), Oxford Knee Score (OKS), range of motion (ROM). Results All 74 patients were followed up for (2.38 ± 0.33) years. The operation time, blood loss during operation, incision length and VAS score after operation in the LUKA group were significantly less than those in the TKA group and LCCK group (P 0.05). Conclusion LUKA, TKA and LCCK arthroplasty have good clinical effect in the treatment of LCKOA; Compared with TKA and LCCK arthroplasty, LUKA has the advantages of less trauma, less bleeding, less pain and quick recovery. The short-term effect is satisfactory, and the long-term effect remains to be observed.

The rapid development of cross-border e-commerce (CBEC) has enabled more suppliers to expand into overseas markets, meeting increasingly diverse consumer demands. Selecting an effective logistics mode is a crucial issue for suppliers, yet uncertainty in demand and exchange rate fluctuations make this problem challenging. This paper considers a supply chain consisting of a supplier and a CBEC platform. Using a distributionally robust optimization approach, we provide optimal overseas warehousing strategies and logistics mode selection for suppliers, given partial distribution information of market demand and exchange rate, such as means, variances, and covariances. It is found that when demand and exchange rate fluctuations are small, the supplier chooses the bonded warehouse logistics mode to reduce costs. Conversely, when demand and exchange rate fluctuations increase, the supplier opts for the direct mail mode to respond flexibly to market risk. The correlation between exchange rate and demand also affects the choice of logistics mode. Specifically, with low correlation, the preference is for the bonded warehouse mode, whereas high correlation leads suppliers to choose the direct mail mode. In addition, the impact of demand and exchange rate fluctuations on suppliers’ overseas warehousing volumes depends on the product’s profit margin. These findings provide guidance for the selection of CBEC logistics under exchange rate risk.

Abstract Background Uncertainty remains about the long-term effects of air pollutants (AP) on multiple diseases, especially subtypes of cardiovascular disease (CVD). We aimed to assess the individual and joint associations of fine particulate matter (PM2.5), along with its chemical components, nitrogen dioxide (NO2) and ozone (O3), with risks of 32 health conditions. Methods A total of 17,566 participants in Sichuan Province, China, were included in 2018 and followed until 2022, with an average follow-up period of 4.2 years. The concentrations of AP were measured using a machine-learning approach. The Cox proportional hazards model and quantile g-computation were applied to assess the associations between AP and CVD. Results Per interquartile range (IQR) increase in PM2.5 mass, NO2, O3, nitrate, ammonium, organic matter (OM), black carbon (BC), chloride, and sulfate were significantly associated with increased risks of various conditions, with hazard ratios (HRs) ranging from 1.06 to 2.48. Exposure to multiple air pollutants was associated with total cardiovascular disease (HR 1.75, 95% confidence intervals (CIs) 1.62–1.89), hypertensive diseases (1.49, 1.38–1.62), cardiac arrests (1.52, 1.30–1.77), arrhythmia (1.76, 1.44–2.15), cerebrovascular diseases (1.86, 1.65–2.10), stroke (1.77, 1.54–2.03), ischemic stroke (1.85, 1.61–2.12), atherosclerosis (1.77, 1.57–1.99), diseases of veins, lymphatic vessels, and lymph nodes (1.32, 1.15–1.51), pneumonia (1.37, 1.16–1.61), inflammatory bowel diseases (1.34, 1.16–1.55), liver diseases (1.59, 1.43–1.77), type 2 diabetes (1.48, 1.26–1.73), lipoprotein metabolism disorders (2.20, 1.96–2.47), purine metabolism disorders (1.61, 1.38–1.88), anemia (1.29, 1.15–1.45), sleep disorders (1.54, 1.33–1.78), renal failure (1.44, 1.21–1.72), kidney stone (1.27, 1.13–1.43), osteoarthritis (2.18, 2.00–2.39), osteoporosis (1.36, 1.14–1.61). OM had max weights for joint effects of AP on many conditions. Conclusions Long-term exposure to increased levels of multiple air pollutants was associated with risks of multiple health conditions. OM accounted for substantial weight for these increased risks, suggesting it may play an important role in these associations.

Abstract Background Bi-allelic variants in DNAH11 have been identified as causative factors in Primary Ciliary Dyskinesia, leading to abnormal respiratory cilia. Nonetheless, the specific impact of these variants on human sperm flagellar and their involvement in male infertility remain largely unknown. Methods A collaborative effort involving two Chinese reproductive centers conducted a study with 975 unrelated infertile men. Whole-exome sequencing was employed for variant screening, and Sanger sequencing confirmed the identified variants. Morphological and ultrastructural analyses of sperm were conducted using Scanning Electron Microscopy and Transmission Electron Microscopy. Western Blot Analysis and Immunofluorescence Analysis were utilized to assess protein levels and localization. ICSI was performed to evaluate its efficacy in achieving favorable pregnancy outcomes for individuals with DNAH11 variants. Results In this study, we identified seven novel variants in the DNAH11 gene in four asthenoteratozoospermia subjects. These variants led the absence of DNAH11 proteins and ultrastructure defects in sperm flagella, particularly affecting the outer dynein arms (ODAs) and adjacent structures. The levels of ODA protein DNAI2 and axoneme related proteins were down regulated, instead of inner dynein arms (IDA) proteins DNAH1 and DNAH6. Two out of four individuals with DNAH11 variants achieved clinical pregnancies through ICSI. The findings confirm the association between male infertility and bi-allelic deleterious variants in DNAH11, resulting in the aberrant assembly of sperm flagella and contributing to asthenoteratozoospermia. Importantly, ICSI emerges as an effective intervention for overcoming reproductive challenges caused by DNAH11 gene variants.

Abstract Background Differences of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. In more than 50% of human DSD cases, a molecular diagnosis is not available. In intensively farmed pig populations, the incidence of XX DSD pigs is relatively high, leading to economic losses for pig breeders. Interestingly, in the majority of 38, XX DSD pigs, gonads still develop into testis-like structures or ovotestes despite the absence of the testis-determining gene (SRY). However, the current understanding of the molecular background of XX DSD pigs remains limited. Methods Anatomical and histological characteristics of XX DSD pigs were analysed using necropsy and HE staining. We employed whole-genome sequencing (WGS) with 10× Genomics technology and used de novo assembly methodology to study normal female and XX DSD pigs. Finally, the identified variants were validated in 32 XX DSD pigs, and the expression levels of the candidate variants in the gonads of XX DSD pigs were further examined. Results XX DSD pigs are characterised by the intersex reproductive organs and the absence of germ cells in the seminiferous tubules of the gonads. We identified 4,950 single-nucleotide polymorphisms (SNPs) from non-synonymous mutations in XX DSD pigs. Cohort validation results highlighted two specific SNPs, “c.218T > C” in the “Interferon-induced transmembrane protein 1 gene (IFITM1)” and “c.1043C > G” in the “Newborn ovary homeobox gene (NOBOX)”, which were found exclusively in XX DSD pigs. Moreover, we verified 14 candidate structural variants (SVs) from 1,474 SVs, identifying a 70 bp deletion fragment in intron 5 of the WW domain-containing oxidoreductase gene (WWOX) in 62.5% of XX DSD pigs. The expression levels of these three candidate genes in the gonads of XX DSD pigs were significantly different from those of normal female pigs. Conclusion The nucleotide changes of IFITM1 (c.218T > C), NOBOX (c.1043 C > G), and a 70 bp deletion fragment of the WWOX were the most dominant variants among XX DSD pigs. This study provides a theoretical basis for better understanding the molecular background of XX DSD pigs. Plain language summary DSD are conditions affecting development of the gonads or genitalia. These disorders can happen in many different types of animals, including pigs, goats, dogs, and people. In people, DSD happens in about 0.02–0.13% of births, and in pigs, the rate is between 0.08% and 0.75%. Pigs have a common type of DSD where the animal has female chromosomes (38, XX) but no SRY gene, which is usually found on the Y chromosome in males. XX DSD pigs may look like both males and females on the outside and have testis-like or ovotestis (a mix of ovary and testis) gonads inside. XX DSD pigs often lead to not being able to have piglets, slower growth, lower chance of survival, and poorer meat quality. Here, we used a method called whole-genome de novo sequencing to look for variants in the DNA of XX DSD pigs. We then checked these differences in a larger group of pigs. Our results reveal the nucleotide changes in IFITM1 (c.218T > C), NOBOX (c.1043 C > G), and a 70 bp deletion fragment in intron 5 of the WWOX, all linked to XX DSD pigs. The expression levels of these three genes were also different in the gonads of XX DSD pigs compared to normal female pigs. These variants are expected to serve as valuable molecular markers for XX DSD pigs. Because pigs are a lot like humans in their genes, physiology, and body structure, this research could help us learn more about what causes DSD in people.

The development of pipeline steels with exceptional cryogenic toughness is deemed imperative for their applications in various engineering fields. In this work, API X65 steel with lamellar grain (LG) structure is constructed through warm deformation techniques. Comparative analysis with raw API X65 steel revealed notable enhancements in both yield strength (YS) and ultimate strength (UTS), exhibiting increments of 315 MPa and 164 MPa, respectively, while retaining substantial fracture toughness (KIc = 251.14 MPa m0.5). Remarkably, the LG steel exhibits a distinct absence of a ductile-brittle transition behavior over a wide temperature range, maintaining an exceptionally high impact energy from room temperature (RT) to liquid nitrogen temperature (LNT), and the Charpy impact energy exceeding 330 J at LNT, nearly 16 times higher than the raw API X65 steel. This performance can be primarily attributed to the superior plastic deformation capability, coupled with the delamination toughening mechanism. The resultant tortuous path of crack propagation effectively facilitates the absorption of substantial energy, decreases notch tip sensitivity depending on the temperature, stress triaxiality, and strain rate, thereby fostering excellent cryogenic toughness.

Abstract Depression is a prevalent and intricate mental disorder. The involvement of small RNA molecules, such as microRNAs in the pathogenesis and neuronal mechanisms underlying the depression have been documented. Previous studies have demonstrated the involvement of microRNA-143-3p (miR-143-3p) in the process of fear memory and pathogenesis of ischemia; however, the relationship between miR-143-3p and depression remains poorly understood. Here we utilized two kinds of mouse models to investigate the role of miR-143-3p in the pathogenesis of depression. Our findings reveal that the expression of miR-143-3p is upregulated in the ventral hippocampus (VH) of mice subjected to chronic restraint stress (CRS) or acute Lipopolysaccharide (LPS) treatment. Inhibiting the expression of miR-143-3p in the VH effectively alleviates depressive-like behaviors in CRS and LPS-treated mice. Furthermore, we identify Lasp1 as one of the downstream target genes regulated by miR-143-3p. The miR-143-3p/Lasp1 axis primarily affects the occurrence of depressive-like behaviors in mice by modulating synapse numbers in the VH. Finally, miR-143-3p/Lasp1-induced F-actin change is responsible for the synaptic number variations in the VH. In conclusion, this study enhances our understanding of microRNA-mediated depression pathogenesis and provides novel prospects for developing therapeutic approaches for this intractable mood disorder.

In this commentary, we elucidate two distinctive characteristics of China's primary health care system relative to the global primary health care framework: a more narrowly defined patient population and scope of services, along with a diminished clinical capacity in primary care. Building upon this foundation, we critically examine and juxtapose the two quintessential theoretical-practical models of the 20th century that are intimately linked with the integration of medication and prevention. They are the "Community-Oriented Primary Care" Model and the "Barefoot Doctor" Model. Additionally, leveraging a series of practical cases observed within Shanghai's primary care settings in the fourth quarter of 2023, we deliberate on viable approaches for adapting and applying these models in China's primary care infrastructure. We further delineate the requisite external conditions for such a transformation and offer targeted recommendations for the deployment of these models across diverse locales.

Abstract Background Surgery is the primary treatment for non-small cell lung cancer (NSCLC), but microscopic residual disease may be unavoidable. Preclinical studies have shown that volatile anesthetics might suppress host immunity and promote a pro-malignant environment that supports cancer cell proliferation, migration, and angiogenesis, whereas propofol may preserve cell-mediated immunity and inhibit tumor angiogenesis. However, clinical evidence that propofol-based total intravenous anesthesia (TIVA) can reduce tumor recurrence after curative resection remains inconsistent due to the retrospective observational nature of previous studies. Therefore, we will test the hypothesis that the recurrence-free survival (RFS) after curative resection of NSCLC is higher in patients who received TIVA than volatile anesthetics (GAS) in this multicenter randomized trial. Methods This double-blind, randomized trial will enroll patients at 22 international sites, subject to study registration, institutional review board approval, and patient written informed consent. Eligible patients are adult patients undergoing lung resection surgery with curative intent for NSCLC. Exclusion criteria will be contraindications to study drugs, American Society of Anesthesiologists physical status IV or higher, or preexisting distant metastasis or malignant tumor in other organs. At each study site, enrolled subjects will be randomly allocated into the TIVA and GAS groups with a 1:1 ratio. This pragmatic trial does not standardize any aspect of patient care. However, potential confounders will be balanced between the study arms. The primary outcome will be RFS. Secondary outcomes will be overall survival and complications within postoperative 7 days. Enrollment of 5384 patients will provide 80% power to detect a 3% treatment effect (hazard ratio of 0.83) at alpha 0.05 for RFS at 3 years. Discussion Confirmation of the study hypothesis would demonstrate that a relatively minor and low-cost alteration in anesthetic management has the potential to reduce cancer recurrence risk in NSCLC, an ultimately fatal complication. Rejection of the hypothesis would end the ongoing debate about the relationship between cancer recurrence and anesthetic management. Trial registration The study protocol was prospectively registered at the Clinical trials ( https://clinicaltrials.gov , NCT06330038, principal investigator: Hyun Joo Ahn; date of first public release: March 25, 2024) before the recruitment of the first participant.

Abstract Using a symmetry-preserving formulation of a vector $$\,\times \,$$ × vector contact interaction (SCI) and treating the proton as a quark + interacting-diquark bound state, whose structure is obtained by solving a Poincaré-covariant Faddeev equation, we provide a comprehensive, coherent set of predictions for unpolarised and polarised proton parton distribution functions (DFs): valence, glue, and four-flavour separated sea. The results enable many themes to be addressed, including: the asymmetry of antimatter in the proton; the neutron:proton structure function ratio; helicity retention in hard scattering processes; the charm quark momentum fraction; the sign and size of the polarised gluon DF; and the origin of the proton spin. In all cases where sound analyses of data are available, SCI predictions are semiquantitatively in agreement with the results. Those mismatches which exist are typically attributable to the momentum-independence of the underlying interaction. Judiciously interpreted, the SCI delivers a sound and insightful explanation of proton structure as expressed in DFs.

Water is a vital resource on the earth, serving as the foundation of life and playing a crucial role in our daily activities. Perfluorooctanoic acid (PFOA) is an organic compound, which poses a significant threat to the environment due to its persistence and bioaccumulation. PFOA exhibits various toxicities, including neurotoxicity, immunotoxicity, and carcinogenicity. It has been detected in worldwide of air and water samples, as it can easily move through different environmental media such as water, soil, and the atmosphere. The widespread distribution of PFOA in these media poses potential risks to both ecosystems and human health over the long term. Therefore, it is of utmost importance to develop a rapid detection method for accurately monitoring PFOA levels in water. In this study, the electrospray extraction ionization-tandem mass spectrometry (EESI-MS/MS) technique was utilized to directly and rapidly detect PFOA in tap water and river water. To achieve the highest ionization efficiency of PFOA in EESI-MS/MS across different water samples, the experimental parameters such as ion transfer tube temperature, spray voltage, electrospray solvent flow rate, and sample flow rate were optimized. The optimal conditions were temperature of 200 °C for the ion transfer tube, spray voltage of 2 kV, electrospray solvent flow rate of 4 µL/min, and sample flow rate of 6 µL/min. The experiments were conducted under negative ion mode with a mass scan range of m/z 50-500. Methanol solution was used as the electrospray solvent, and collision-induced dissociation (CID) was employed. The secondary characteristic fragment ion m/z 369 of m/z 413 for qualitative and quantitative analysis, enabling direct and rapid detection of PFOA in various water samples. The experimental results demonstrated good linearity of PFOA in the concentration range of 1-500 ng/L, with a linear correlation coefficient (R2) of 0.9976. The detection limit (LOD) of the proposed method is 0.57 ng/L, and the limit of quantification (LOQ) is 1.73 ng/L. The recovery rate ranges from 92.1% to 105.2%, with a relative standard deviation (RSD, n=6) of 1.89%-5.45%. In summary, this method has the advantages of high sensitivity, accuracy, and fast analysis speed, without the need of sample pretreatment. The established EESI-MS/MS method can be effectively applied for direct and rapid detection of PFOA in different water samples, showing promising prospects for monitoring environmental water pollutants. Moreover, it provides valuable references and technical means for the detection of other pollutants.

This study investigates the influence of extrusion conditions on the microstructure and tensile properties of Mg–6Al–0.3Mn–0.3Ca–0.2Y (SEN6) alloy, which is processed at various extrusion temperatures and ratios. An increase in both the extrusion temperature and ratio facilitates dynamic recrystallization during hot extrusion by enhancing thermal and strain energies, increasing the area fraction of recrystallized grains within the extruded material. As either the extrusion temperature or ratio increases, lattice rotation within the recrystallized grains intensifies, resulting in a stronger basal texture in the extruded material. During extrusion, the undissolved Al2Y, Al8Mn4Y, and Al2Ca particles within the billets are partially fragmented and realigned along the extrusion direction. However, the quantity, size, and dispersion of these particles are largely unaffected by variations in extrusion temperature and ratio. The tensile yield strength of the extruded material shows a positive correlation with increasing extrusion temperature and ratio, predominantly due to enhanced texture hardening. Specifically, the tensile yield strength of the material extruded at 400 °C with an extrusion ratio of 25 is 23.2 MPa higher than that of the material extruded at 300 °C with an extrusion ratio of 10. Despite the presence of non-recrystallized grains in materials extruded at the lower extrusion ratio of 10, compression and double twins form uniformly throughout the material during tension, as the widths of non-recrystallized grains are similar to those of recrystallized grains. Consequently, all extruded materials exhibit high tensile elongations, exceeding 20%.

Abstract Background The high prevalence of diabetic kidney disease (DKD) in the United States necessitates further investigation into its impact on complications associated with total hip arthroplasty (THA). This study utilizes a large nationwide database to explore risk factors in DKD cases undergoing THA. Methods This research utilized a case–control design, leveraging data from the national inpatient sample for the years 2016 to 2019. Employing propensity score matching (PSM), patients diagnosed with DKD were paired on a 1:1 basis with individuals free of DKD, ensuring equivalent age, sex, race, Elixhauser Comorbidity Index (ECI), and insurance coverage. Subsequently, comparisons were drawn between these PSM-matched cohorts, examining their characteristics and the incidence of post-THA complications. Multivariate logistic regression analysis was then employed to evaluate the risk of early complications after surgery. Results DKD's prevalence in the THA cohort was 2.38%. A 7-year age gap separated DKD and non-DKD patients (74 vs. 67 years, P

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is implicated in the pathogenesis and progression of autoimmune disease. Patients with rheumatoid arthritis (RA) are at high risk of developing atrial fibrillation (AF), while whether PCSK9 is involved in the onset of AF among RA patients remains unclear. Objectives: To explore the role of PCSK9 in the occurrence of AF in RA patients and decipher the underlying mechanism. Methods: We established a rat model of collagen-induced arthritis (CIA) by immunization with type II collagen in Freund’s incomplete adjuvant. Atrial electrophysiological test was used to evaluate AF susceptibility. We performed a clinical study to examine the correlation between PCSK9 level and AF, which recruited healthy control, RA patients and RA patients complicated with AF. Evolocumab (a monoclonal antibody of PCSK9) is administered via intraperitoneal injection in CIA rats to assess the role of PCSK9 in RA-related AF. LPS-RS (LPS inhibitor), clodronate liposomes (depletion of macrophages), and cell co-culture model were used to dissect the mechanism underlying PCSK9 promotes AF. Results: AF inducibility and duration were higher in CIA rats, accompanied by elevated plasma and atrial PCSK9. Interestingly, compared with healthy control subjects, patients with RA showed an increase in PCSK9, and the PCSK9 is much higher in RA patients complicated with AF. The level of PCSK9 was independently associated with AF risk in RA patients. In the in vivo experiment, evolocumab reduced AF susceptibility, and ameliorated atrial structural remodeling of CIA rats. Mechanistically, augmented LPS in CIA rats led to an increase in PCSK9, which exacerbated fibrosis of cardiac fibroblasts and apoptosis of cardiac myocytes by enhancement of M1 macrophages polarization and inflammation, thereby contributing to AF. Conclusion: This study suggests that elevated PCSK9 causes atrial structural remodeling by enhancement of M1 macrophages polarization in atria, and evolocumab can effectively protects CIA rats from AF.

Abstract Introduction Research has highlighted the role of runt-related transcription factor 2 (Runx2) in the development of osteoarthritis (OA); however, its causal association remains unclear. This study aimed to explore whether Runx2 expression is causally associated with OA and assess its therapeutic potential for OA. Methods Genetic proxy instruments for Runx2 expression were obtained from gene expression quantitative trait locus (eQTLs) study of eQTLGen Consortium (n = 31,684). Aggregated genome-wide association study (GWAS) data for OA (including all OA [177,517 cases and 649,173 controls], knee OA (KOA) [62,497 cases and 333,557 controls], and hip OA (HOA) [36,445 cases and 316,943 controls]) were extracted from the Genetics of Osteoarthritis Consortium. We integrated eQTLs data with OA GWAS data to estimate their causal association and to estimate the potential of Runx2 as a drug target in the treatment of OA using summary data-based Mendelian randomization (SMR) analysis. Furthermore, different OA GWAS data (including all OA [77,052 cases and 378,169 controls], KOA [24,955 cases and 378,169 controls], and HOA [15,704 cases and 378,169 controls]) derived from the GWAS Catalog database were used for replication study. Results SMR analysis showed that high expression levels of Runx2 were associated with an increased risk of all OA [odds ratio (OR) 1.044, 95% confidence interval (CI) 1.023–1.067; P = 5.03 × 10−5], KOA (OR 1.040, 95% CI 1.006–1.075; P = 0.021), and HOA (OR 1.067, 95% CI 1.022–1.113; P = 0.003). This suggests that Runx2 inhibitors may have promising potential for the treatment of OA. Notably, the causal effects of Runx2 with all OA (OR 1.053, 95% CI 1.027–1.079; P = 3.95 × 10−5) and KOA (OR 1.043, 95% CI 1.001–1.087; P = 0.045) were repeated in the replication study, but limited evidence supported the association of Runx2 expression levels with HOA (OR 1.045, 95% CI 0.993–1.101; P = 0.094). Conclusions Our analyses indicate a positive correlation between Runx2 expression and OA risk across all three phenotypes, suggesting the potential of Runx2 inhibitors in the treatment of OA and providing evidence from a genetic perspective.

To investigate the multiscale interaction characteristics of Landfall Typhoon Lekima (2019), this study analyzed the characteristics of the different scale vortex structure and interactions among different scales based on vorticity equation diagnosis. The analysis is based on the simulation results of the WRF model which has been thoroughly verified. The main results are as follows: the original vorticity dominated by the meso-α scale vorticity increases with height and then decreases, with maximum vorticity distributed at 900 hPa. The meso-β scale vorticity varies significantly with altitude, while the meso-γ scale vorticity field exhibits obvious positive vorticity below 850 hPa. The meso-α scale vorticity tendency primarily maintains negative, contributing significantly to the overall reduction in the original vorticity field over time. The increase in mid-to-upper-level (above 550 hPa) original vorticity is mainly related to the variations in the meso-β and meso-γ scale vorticity fields. The original vorticity dominated by the meso-α scale vorticity increases with height and then decreases, and the whole layer vorticity decreases over time. The meso-β scale vorticity varies significantly with altitude and time, while the meso-γ scale vorticity field consistently exhibits significant positive vorticity below 850 hPa. The vorticity equation diagnosis revealed that the primary source terms of the vorticity tendencies are the twisting and stretching terms, and the main sink terms being horizontal and vertical vorticity transport terms below 900 hPa. The source terms and sink terms exchange above 850 hPa. Scale separation results show that the primary contributions of all impact factors originate from the meso-α and meso-γ scale fields (accounting for over 80% of the total), with the contribution of the meso-α scale being less than that of the meso-γ scale and a notable contribution over 35.5% of the interactions between different scales.

Based on the best-track dataset from the Shanghai Typhoon Institute/China Meteorological Administration, the paper provides a comprehensive summary and analysis of tropical cyclone (TC) activities in the Western North Pacific (WNP) and the South China Sea (SCS) for 2022. Using the historical climatology from 1951 to 2020, the anomalous conditions during 2022 in TC frequency, origin locations, tracks, intensity, and duration for the entire ocean basin as well as landfall events in China are examined. Results show that the overall TC frequency is slightly lower than normal, but the multiple TC events have a very high frequency of occurrence. Origin locations of TCs, which mark the starting points of their paths, show a large westward and northward deviation from climatology. Around 40% of the named TCs exhibit a shift in their direction of movement from westerly to easterly. Additionally, comparisons of the means, medians, upper and lower quartiles all indicate that the intensity of TCs in 2022 is generally lower than the climatology, with the duration of TCs at tropical storm intensity or above being shorter than usual. A notable observation is the fewer incidence of TC landfalls in China, but with a geographical concentration in Guangdong Province. These anomalous annual TC activities are influenced by related atmospheric and oceanic environmental conditions modulated by multi-scale climate variability. The findings provide useful information for enhancing disaster mitigation strategies in the Asia-Pacific region.

Purpose: For many decades, patients recovering from wound closure have been instructed not to bathe. Although studies have shown that earlier postoperative bathing does not increase the risk of wound infection, it remains rare in practice for patients to be allowed earlier postoperative bathing. We performed this meta-analysis to determine how earlier bathing affected rates of wound infection, other complications, and patient satisfaction. Methods: This systematic review conforms to PRISMA guidelines. The PubMed, EMBASE, Medline, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from their inception dates to December 31, 2022. We estimated pooled values for the efficacy of trial of earlier bathing versus delayed bathing using the odds ratio and their associated 95% CI, and we used the I2 statistic to assess heterogeneity between studies contributing to these estimates. Results: Of the 1813 articles identified by our search, 11 randomized controlled trials including 2964 patients were eligible for inclusion. The incidence of wound infection did not differ significantly between the earlier bathing and delayed bathing groups, nor did rates of other wound complications such as redness and swelling, or wound dehiscence. However, the incidence of hematoma in the delayed bathing group was higher than in the earlier bathing group. Reported patient satisfaction was significantly higher in the earlier bathing group. Conclusion: The medical community, health authorities, and government should create and disseminate clinical practice guidelines to guide patients to evidence-based beneficial treatment.

Magnesium (Mg) and its alloys, as the lightest metal structural materials, are significantly attractive for lightweight applications. However, the extrudability of commercial Mg alloys is obviously poor compared with Al alloys, which has greatly restricted their widespread application so far. To further expand the industry uptake of Mg alloy extrusion components, development of the low-cost, high speed extrudable Mg alloys with good mechanical performance is strongly desired. In this review, the factors determining the extrudability of Mg alloys are critically analysed. Besides, recent research highlights on high speed extrudable Mg alloys are systematically reviewed from the perspective of the alloying systems, specifically focusing on Mg–Al, Mg–Zn, Mg–Sn, Mg–Bi and Mg–RE based alloys. Furthermore, the new alloy design concepts and novel extrusion processing routes are critically analysed and summarized, and also the recommendations for future research prospects for high speed extrudable Mg alloys are also suggested. We hope this review will inspire new ideas on both composition design and technology innovation for developing high speed extrudable Mg alloys with excellent strength-ductility synergy.

Abstract Background Cervical cancer is a prevalent malignancy of the female reproductive system. Cervical intraepithelial neoplasia (CIN) is a precursor lesion for CC. Various studies have examined circulating microRNAs (miRNAs) as potential early diagnostic markers for CC and CIN. However, the findings have been inconclusive. Therefore, it is necessary to evaluate the diagnostic accuracy and identify potential sources of variability among these studies. Methods: The PubMed, Cochrane Library, Embase, and Web of Science databases were searched to identify relevant literature. Then, Stata 14.0 was utilized to calculate summary estimates for diagnostic parameters, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic (ROC). To scrutinize the heterogeneity, the Cochran-Q test and I2 statistic were utilized. As significant heterogeneity was observed, the random effects model was chosen. To explore potential sources of the heterogeneity, subgroup and regression analyses were conducted. Results: We analysed 12 articles reporting on 24 studies involving 1817 patients and 1731 healthy controls. The pooled sensitivity was 0.77 (95% CI 0.73–0.81), the specificity was 0.81 (95% CI 0.73–0.86), the PLR was 3.99 (95% CI 2.81–5.65), the NLR was 0.28 (95% CI 0.23–0.35), the DOR was 14.18 (95% CI 8.47–23.73), and the area under the curve (AUC) was 0.85 (95% CI 0.81–0.87). Subgroup analysis revealed that multiple miRNAs can improve diagnostic performance; the pooled sensitivity of multiple miRNAs was 0.78 (95% CI 0.68–0.86), the specificity was 0.85 (95% CI 0.78–0.90), and the AUC was 0.89 (95% CI 0.86–0.91). Conclusion: This study suggested that circulating microRNAs may be biomarkers for early CC diagnosis.

Abstract Ficus species (Moraceae) play pivotal roles in tropical and subtropical ecosystems. Thriving across diverse habitats, from rainforests to deserts, they harbor a multitude of mutualistic and antagonistic interactions with insects, nematodes, and pathogens. Despite their ecological significance, knowledge about the genomic background of Ficus remains limited. In this study, we report a chromosome-level reference genome of F. hirta, with a total size of 297.27 Mb, containing 28,625 protein-coding genes and 44.67% repeat sequences. These findings illuminate the genetic basis of Ficus responses to environmental challenges, offering valuable genomic resources for understanding genome size, adaptive evolution, and co-evolution with natural enemies and mutualists within the genus.

Abstract Low-grade glioma (LGG) is heterogeneous at biological and transcriptomic levels, and it is still controversial for the definition and typing of LGG. Therefore, there is an urgent need for specific and practical molecular signatures for accurate diagnosis, individualized therapy, and prognostic evaluation of LGG. Cell death is essential for maintaining homeostasis, developing and preventing hyperproliferative malignancies. Based on diverse programmed cell death (PCD) related genes and prognostic characteristics of LGG, this study constructed a model to explore the mechanism and treatment strategies for LGG cell metastasis and invasion. We screened 1161 genes associated with PCD and divided 512 LGG samples into C1 and C2 subtypes by consistent cluster analysis. We analyzed the two subtypes' differentially expressed genes (DEGs) and performed functional enrichment analysis. Using R packages such as ESTIMATE, CIBERSOTR, and MCPcounter, we assessed immune cell scores for both subtypes. Compared with C1, the C2 subtype has a poor prognosis and a higher immune score, and patients in the C2 subtype are more strongly associated with tumor progression. LASSO and COX regression analysis screened four characteristic genes (CLU, FHL3, GIMAP2, and HVCN1). Using data sets from different platforms to validate the four-gene feature, we found that the expression and prognostic correlation of the four-gene feature had a high degree of stability, showing stable predictive effects. Besides, we found downregulation of CLU, FHL3, and GIMAP2 significantly impairs the growth, migration, and invasive potential of LGG cells. Take together, the four-gene feature constructed based on PCD-related genes provides valuable information for further study of the pathogenesis and clinical treatment of LGG.

Abstract 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.

Abstract Background Hypoxia inducible factor‐1α (HIF‐1α) is a sensitive indicator of oxygen homeostasis, of which the expression elevates following hypoxia/ischemia. This study reveals the specific mechanisms underlying the effects of HIF‐1α on ischemic stroke (IS). Methods IS model was established using middle cerebral artery occlusion (MCAO)‐modeled male rats and oxygen glucose deprivation/reoxygenation (OGD/R)‐treated mice hippocampal cells HT22, followed by the silencing of HIF‐1α and the overexpression of C‐X‐C motif chemokine receptor 4 (CXCR4) and nuclear factor‐kappa B (NF‐κB). Following the surgery, Garcia's grading scale was applied for neurological evaluation. Cerebral infarcts and injuries were visualized using 2,3,5‐triphenyltetrazolium chloride and hematoxylin‐eosin staining. The levels of tumor necrosis factor‐α, Interleukin (IL)‐6, IL‐1β, malondialdehyde, and 8‐hydroxy‐2′‐deoxyguanosine, were calculated via ELISA. MTT assay and lactate dehydrogenase (LDH) assay kit were adopted to determine the viability and cytotoxicity of OGD/R‐modeled cells. Reactive oxygen species (ROS) generation was evaluated using a 2′‐7′dichlorofluorescin diacetate (DCFH‐DA) probe. The levels of HIF‐1α, CXCR4, and NF‐κB p65 were quantified via Western blot and immunofluorescence, respectively. Results HIF‐1α knockdown improved Garcia's score, attenuated the cerebral infarct, inflammation, and ROS generation, and alleviated the levels of inflammatory cytokines and CXCR4/NF‐κB p65 in MCAO‐modeled rats. Such effects were reversed following the overexpression of CXCR4 and NF‐κB. Also, in OGD/R‐treated HT22 cells, HIF‐1α silencing diminished the cytotoxicity and ROS production and reduced the expressions of CXCR4/NF‐κB p65, while promoting viability. However, CXCR4/NF‐κB p65 overexpression did the opposite. Conclusion HIF‐1α knockdown alleviates inflammation and oxidative stress in IS through the CXCR4/NF‐κB pathway.

BackgroundThis study evaluates tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interferon-γ-induced protein-10 (IP-10) in pregnant women with COVID-19 and their newborns, exploring the effects of antiviral treatments and vaccine-induced neutralizing antibody (Nab) inhibition on these key viral infection biomarkers.MethodsWe studied 61 pregnant women with past COVID-19 and either three (n=56) or four (n=5) doses of vaccination, and 46 without COVID-19 but vaccinated. We analyzed them and their newborns’ blood for TRAIL, IP-10, and Nab levels using enzyme-linked immunosorbent assays (ELISA), correlating these with other clinical factors.ResultsOur study found lower TRAIL but higher IP-10 levels in maternal blood than neonatal cord blood, irrespective of past COVID-19 diagnosis. Cases diagnosed with COVID-19 < 4 weeks previously had higher maternal blood TRAIL levels (16.49 vs. 40.81 pg/mL, p=0.0064) and IP-10 (154.68 vs. 225.81 pg/mL, p=0.0170) than those never diagnosed. Antiviral medication lowered TRAIL and IP-10 in maternal blood without affecting Nab inhibition (TRAIL: 19.24 vs. 54.53 pg/mL, p=0.028; IP-10: 158.36 vs. 255.47 pg/mL, p=0.0089). TRAIL and IP-10 levels were similar with three or four vaccine doses, but four doses increased Nab inhibition (p=0.0363). Previously COVID-19 exposed pregnant women had higher Nab inhibition (p < 0.0001). No obvious correlation was found among TRAIL, IP-10, and Nab inhibition level.ConclusionsOur study suggests that lower maternal TRAIL and higher IP-10 levels compared to neonatal cord blood coupled with a rise in both markers following COVID-19 diagnosis that could be reduced by antivirals indicates a correlation to infection severity. Higher vaccine doses enhance Nab inhibition, irrespective of antiviral medication use and independent of TRAIL or IP-10 levels, highlighting the significance and safety of adequate vaccination and antiviral use post-diagnosis in pregnant women.

Background: Superior mesenteric ischemia/reperfusion (I/R) causes barrier dysfunction and facilitates bacterial translocation (BT) in the small intestine, which can even lead to systemic sepsis. Our previous research showed that luminal administration of glucose and its anaerobic glycolytic metabolites exerted cytoprotective effects on epithelial cells and ameliorated I/R-induced BT in the liver and spleen. Notably, the reduction of BT occurs over the whole intestinal tract, not only restricted in the ligated glucose-containing loop. Objectives: In this study, we hypothesized that local jejunal glucose-contacting might confer on the remote intestinal epithelium regeneration potential, fortify their barrier function and goblet cell secretory activity. Methods: Two 10-cm jejunal segments were isolated in Wistar rats. One segment was ligatured at both ends and infused with Krebs buffer containing 0- or 50-mM glucose (local loop), whereas the adjacent segment was left unaltered and not exposed to glucose (remote loop). The rats then underwent either a sham operation or I/R challenge by occlusion of the superior mesenteric artery for 20 min, followed by reperfusion for 1 h. Results: Enteral addition of glucose in the local jejunum loop alleviated ischemia-induced barrier defects, histopathological scores, cell death, and mucosal inflammation (myeloperoxidase and inflammatory cytokine production) in the remote jejunum. After ischemia, goblet cells in the remote jejunum showed cavitation of mucin granules and low MUC2 expression. Local addition of glucose enhanced MUC2 synthesis and stimulated a jet-like mucus secretion in the remote jejunum, which was accompanied by the restoration of crypt activity. Conclusions: Our results showed local enteral glucose effectively mitigates I/R-induced barrier dysfunction, suggesting that local glucose-stimulated mucus secretion by remote goblet cells may serve to mitigate mucosal inflammation and BT. We provide a more precise barrier protection role of enteral glucose upon I/R challenge, presenting new opportunities for future therapeutic potential.

Objective: Proopiomelanocortin (POMC) neurons release potent anorexigenic neuropeptides, which suppress food intake and enhance energy expenditure via melanocortin receptors. Although the importance of central melanocortin in physiological regulation is well established, the underlying genetic mechanisms that define the functional identity of melanocortin neurons and maintain hypothalamic Pomc expression remain to be fully determined. In this study, we investigate the functional significance of Six3, a transcriptional regulator notably expressed in embryonic and adult mouse POMC neurons, in the regulation of hypothalamic Pomc expression and downstream physiological consequences. Methods: We first evaluated the expression of Six3 in the developing and adult hypothalamus by double fluorescence in situ hybridization. Next, we assessed POMC immunoreactivity in mutant mice selectively lacking Six3 from Pomc-expressing neurons and quantified Pomc mRNA levels in a tamoxifen-inducible Six3 knockout mouse model activated at embryonic E9.5 days. We also determined glucose and insulin sensitivity, daily food intake, body composition and body weight in adult male and female mice lacking Six3 specifically from POMC neurons. Lastly, we assessed the physiological consequences of ablating Six3 from POMC neurons in adult mice. Results: Six3 and Pomc were co-expressed in mouse hypothalamic neurons during development and adulthood. Mouse embryos deficient in Six3 showed reduced Pomc expression in the developing hypothalamus. Targeted deletion of Six3 specifically from POMC neurons resulted in decreased hypothalamic Pomc expression, increased daily food intake, enhanced glucose sensitivity and mild obesity in male but not in female mice. Finally, conditional removal of Six3 from POMC neurons in adult mice led to a reduction in hypothalamic POMC immunoreactivity with no significant effects in body weight or food intake. Conclusions: Altogether, our results demonstrate that Six3 plays an essential role in the early establishment of POMC neuron identity and the maintenance of physiological levels of hypothalamic Pomc expression. In addition, our study demonstrates that the functional significance of Six3 expression in POMC neurons is sexually dimorphic and age-dependent.

The Western Sichuan Plateau stands as a vital ecological barrier in China. In recent years, rapid urbanization and infrastructure development have led to increased ecosystem fragmentation in the region, compression of species habitats, and significant challenges to ecosystem service functions and biodiversity conservation. Constructing ecological corridors can help maintain landscape connectivity and preserve biodiversity by providing habitats for various species. Additionally, they can enhance population viability and species richness at both local and regional scales. Current research focuses on the construction of ecological networks and the potential impacts of corridors. Few studies consider corridor width as an object of study. This study addresses the width of corridor construction, aiming to support the practical implementation of corridor projects and explore the coordination between corridor costs and functionality at different widths. Based on an evaluation of ecosystem service functions and in conjunction with natural reserves, this study identified significant ecological source. Four primary resistance factors—land use type, elevation, slope, and Degree of relief—were selected to construct resistance surfaces. The MAXENT model is introduced to identify potential landslide-prone areas, and the resistance surfaces are accordingly adjusted. Potential corridors are identified utilising circuit theory. Subsequently, by employing the IEW-TOPSIS model, different ecological corridor widths are evaluated in terms of “cost-function-ecological benefits” to determine suitable corridor widths for the Western Sichuan Plateau. Results reveal significant variations in ecological corridor widths across different regions of the plateau. Taking topographical factors into account, 1400 m emerges as the most optimal width twice, while 800 m, 1700 m, and 2000 m each appear once. The corridor width evaluation system can provide decision support for ecological corridor construction in the Western Sichuan Plateau, contributing to the preservation of ecological security in the Qinghai-Tibet Plateau in China.

Introduction: Gelsemium, a whole grass in the family Loganiaceae, is the world's poisonous plants. Due to its flower's resemblance to honeysuckle, there has been a rise in cases of accidental ingestion of Gelsemium, leading to poisoning and even fatalities in recent years. Although this problem has been apparent for many years, there is now promise that it can be better understood. This work seeks to comprehensively summarizes. Methods: References for this review were collected by searching CNKI (http://www.cnki.com.cn) and PubMed untill 29 October 2023. The selection of articles was performed by reading the title, abstract, and keywords. Results: Gelsedine-type alkaloids are identified as the primary toxic constituents in Gelsemium. Animal experimentation has elucidated the acute neurotoxic impact of Gelsemium, primarily characterized by inhibition of the respiratory center. This effect may be intricately linked to the disruption of GABA/Glu equilibrium and NMDA receptor-mediated excitotoxicity. Some studies have found the potential reduction of toxicity in Gelsemium through processing and compatibility with traditional Chinese Medicine. However, prompt endotracheal intubation and mechanical ventilation are paramount in clinical instances of Gelsemium poisoning. Additionally, there is evidence supporting the efficacy of enhancing CYP3A4/5 enzyme metabolism can diminish the concentration of Gelsemium and mortality rates from poisoning. Discussion: This review provides a summary of clinical symptoms and rescue measures for Gelsemium poisoning, aiming to enhance treatment options and mitigate toxic effects. The elucidation of Gelsemium's neurotoxic mechanism may offer insights for future research, particularly in understanding Gelsemium's regulatory role on GABA receptor and NMDA receptor, which is expected to identify and develop specific antidotes for Gelsemium poisoning.

ObjectivesTo summarize the clinical characteristics, outcomes and identify risk factors of Acinetobacter baumannii (AB) meningitis in children.MethodsThis was a single-center, retrospective study. Children hospitalized between January 2016 and December 2021 who were diagnosed with AB meningitis were included. The clinical characteristics and outcomes were reviewed. Risk factors were determined using univariate analyses (chi-square and Mann-Whitney U tests).ResultsSeventeen patients were included; 15 cases were secondary to neurosurgery, and two were neonates with primary bacterial meningitis. Common symptoms included fever, convulsions and nervous system abnormalities. Cerebrospinal fluid (CSF) tests typically showed increased white blood cell counts dominated by neutrophils, reduced glucose levels and elevated protein levels. Ten patients were successfully treated (successful treatment [ST] group); seven had failed treatment (failed treatment [FT] group). Univariate analyses revealed that mechanical ventilation, routine white cell counts in the peripheral blood, procalcitonin, protein in the CSF, septic shock and carbapenem-resistant AB (CRAB) differed significantly between the groups.ConclusionAB meningitis in children has a high mortality rate. FT was associated with mechanical ventilation, septic shock, CRAB, lower peripheral leukocyte counts, higher protein levels in the CSF and procalcitonin. Larger studies are needed to identify independent risk factors for adverse outcomes.

BackgroundA causal connection between oxidative stress and inflammation in diabetes, along with its associated renal and cardiovascular complications, has been established. Sixteen prescribed potentially renoprotective Chinese herbal medicines for diabetic kidney disease (PRCHMDKD), which are scientific Chinese medicine (botanical drug) and categorized into five classes (clearing heat, nourishing yin, dampness dispelling, tonifying qi, and harmonizing formulas), exhibit shared antioxidative properties and target multiple oxidative stress pathways. However, the time-response, cumulative effects, and safety (hyperkalemia risk) of these sixteen PRCHMDKD on cardiorenal and survival outcomes in patients with overall and advanced DKD remain unresolved.MethodsThis retrospective cohort study analyzed national health insurance claims data in 2000–2017. Four statistical methods, including Cox proportional hazards models, complementary restricted mean survival time (RMST), propensity score matching, and competing risk analysis for end-stage renal disease (ESRD), were employed to investigate this relationship. The study included 43,480 PRCHMDKD users and an equal number of matched nonusers within the overall DKD patient population. For advanced DKD patients, the cohort comprised 1,422 PRCHMDKD users and an equivalent number of matched nonusers.ResultsPRCHMDKD use in overall and advanced, respectively, DKD patients was associated with time-dependent reductions in adjusted hazard ratios for ESRD (0.66; 95% CI, 0.61–0.70 vs. 0.81; 0.65–0.99), all-cause mortality (0.48; 0.47–0.49 vs. 0.59; 0.50–0.70), and cardiovascular mortality (0.50; 0.48–0.53 vs. 0.61; 0.45–0.82). Significant differences in RMST were observed in overall and advanced, respectively, DKD patients, favoring PRCHMDKD use: 0.31 years (95% CI, 0.24–0.38) vs. 0.61 years (0.13–1.10) for ESRD, 2.71 years (2.60–2.82) vs. 1.50 years (1.03–1.98) for all-cause mortality, and 1.18 years (1.09–1.28) vs. 0.59 years (0.22–0.95) for cardiovascular mortality. Additionally, hyperkalemia risk did not increase. These findings remained consistent despite multiple sensitivity analyses. Notably, the cumulative effects of utilizing at least four or five classes and multiple botanical drugs from the sixteen PRCHMDKD provided enhanced renoprotection for patients with both overall and advanced DKD. This suggests that there is involvement of multiple targets within the oxidative stress pathways associated with DKD.ConclusionThis real-world study suggests that using these sixteen PRCHMDKD provides time-dependent cardiorenal and survival benefits while ensuring safety for DKD patients.

BackgroundDuring the coronavirus disease 2019 (COVID-19) pandemic, the infection of Mycoplasma pneumoniae (MP) decreased significantly. At the beginning of the summer of 2023, there was an increasing trend of MP infection in China and the MP pneumonia (MPP) is surging when it comes to the school season and lasts for several months which has attracted widespread attention.ObjectiveThis study aims to investigate the prevalent characteristics of the MP and the difference between the COVID-19 pandemic and the post in Shanghai, China.MethodsThe demographic information and the results of laboratory pathogen detection from July 2021 to May 2024 were collected and analyzed to find out the prevalent characteristics of MP. Two periods, during the COVID-19 pandemic and the post-pandemic, were divided and compared. The P1 genotyping and macrolide resistance-associated gene of 23 s rRNA were detected using the remaining MP-positive samples.ResultsDuring the COVID-19 pandemic, the prevalence of the MP has significantly decreased. Female children are more susceptible to MP infection than the male. The school-aged group (>6 years) had the highest infection rate. The rate of MP P1 genotype during post panel is higher than that during COVID-19 pandemic, which is dominant from July 2021 to May 2024, while the macrolide-resistant associated mutations (A2063G) keep high percentage during or post pandemic.ConclusionAfter the COVID-19 pandemic, an outbreak of MP infection occurred from summer onwards in 2023 with children in Shanghai, China. Immunity debt and high rate of macrolide-resistance may take effects in this MP epidemic. Continuous surveillance of MP is necessary to help to alert the prevalence of MPP.

IntroductionThe introduction of Immune Checkpoint Inhibitors (ICIs) has marked a paradigm shift in treating Lung Squamous Cell Carcinoma (LUSC), emphasizing the urgent need for precise molecular biomarkers to reliably forecast therapeutic efficacy. This study aims to identify potential biomarkers for immunochemotherapy efficacy by focusing on plasma extracellular vesicle (EV)-derived long RNAs (exLRs).MethodsWe enrolled 78 advanced LUSC patients undergoing first-line immunochemotherapy. Plasma samples were collected, and exLR sequencing was conducted to establish baseline profiles. A retrospective analysis was performed on 42 patients to identify differentially expressed exLRs. Further validation of the top differentially expressed exLRs was conducted using quantitative reverse transcription PCR (qRT-PCR). Univariate Cox analysis was applied to determine the prognostic significance of these exLRs. Based on these findings, we developed a predictive signature (p-Signature).ResultsIn the retrospective analysis of 42 patients, we identified 460 differentially expressed exLRs, with pathways related to leukocyte migration notably enriched among non-responders. Univariate Cox analysis revealed 45 exLRs with prognostic significance. The top 6 protein-coding exLRs were validated using qRT-PCR, identifying CXCL8, SSH3, and SDHAF1 as differentially expressed between responders and non-responders. The p-Signature, comprising these three exLRs, demonstrated high accuracy in distinguishing responders from non-responders, with an Area Under the Curve (AUC) of 0.904 in the retrospective cohort and 0.812 in the prospective cohort.DiscussionThis study highlighted the potential of plasma exLR profiles in predicting LUSC treatment efficacy. Intriguingly, lower p-Signature scores were associated with increased abundance of activated CD4+ and CD8+ T cells, indicating a more robust immune environment. These findings suggest that the p-Signature could serve as a valuable tool in guiding personalized and effective therapeutic strategies for LUSC.

Background: To investigate the long-term corneal stromal remodeling and central stromal thickness (CST) reduction accuracy after small-incision lenticule extraction (SMILE) for high myopia correction. Methods: This prospective study included 30 patients (50 eyes) who had undergone SMILE. Measurements of CST reduction using optical coherence tomography were performed at 1 month, 6 months, 1 year, and 3 years after surgery. Correlations were performed between planned and achieved CST reductions. Results: The study enrolled 50 eyes of 30 patients. The mean spherical equivalent was -9.25±1.52 D(diopters). The postoperative CST increased in the first month after surgery and remained stable for a year. Thereafter, it remained stable during follow-up from 1 to 3 years postoperatively. The predicted CST reduction was 146.4 ± 10.3 μm. The achieved CST reductions at 1 month, 6 months, 1 year, and 3 years after surgery were 135.3 ± 12.1 μm, 130.8 ± 10.6 μm, 125.9 ± 9.4 μm, and 122.2 ± 10.6 μm, respectively. An overestimation of CST reduction was observed three years after surgery. Correlation analysis revealed a strong correlation between planned and achieved CST reductions; however, no correlation was found between CST reductions predicted error and the planned CST reductions. Conclusion: During long-term follow-up, our findings revealed a significant stromal remodeling following SMILE in patients with high myopia. Therefore, clinicians should consider it when screening patients with high myopia for SMILE.