Integrating WGCNA and network pharmacology to unravel the multi-target mechanisms of Ludangshen Oral liquid against nephrotic syndrome: Involvement of TGF-β1/Smad3 and gut microbiota.

The present study aimed to assess whether postmortem analysis of aqueous humor in pigs can be used to estimate antemortem serum biochemical values. The experimental design used a control group to establish regression equations linking postmortem aqueous humor to antemortem serum biochemical values. These models enabled reconstruction of the physiological status in decomposed forensic cases associated with heatstroke and hypoxia in pigs that died following a ventilation system failure on a commercial farm, and assessment of physiological distress, cause of death, and potential intentional animal abuse. Concentrations of albumin (ALB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), amylase (AMY), total bilirubin (TBIL), urea nitrogen (UN), creatinine (CRE), calcium (Ca), phosphate (PHOS), sodium (Na), potassium (K), glucose (GLU) and total protein (TP) were measured in aqueous humor and compared with serum samples obtained after slaughter of 30 pigs. Biochemical analyses were performed using a chemistry analyzer with commercial reagent rotors designed. Strong correlations were observed for Na, K and CRE concentrations and for ALT and UN activities between aqueous humor and serum, while TP, ALB, AMY, TBIL and Ca showed weaker associations. Notably, CRE and UN showed strong postmortem correlations with serum values in pigs, consistent with findings in cats and other species, highlighting their reliability as indicators of renal function. Electrolyte concentrations, particularly K and Na, followed consistent and well-recognized patterns described in both human and veterinary forensic studies, with K levels in pigs comparable to those observed in other domestic animals. The results indicate that postmortem aqueous humor analysis of CRE, Na, K, AST, and UN provides a reliable estimation of corresponding serum values in pigs, representing a useful diagnostic and forensic tool in the case of animal welfare.

In recent years, Mycoplasma pneumoniae (MP) has developed widespread resistance to macrolide antibiotics, and second-line anti-Mycoplasma drugs such as levofloxacin have begun to be used in children. However, there is currently insufficient data on their efficacy and safety. To explore the application effect of levofloxacin in children with refractory Mycoplasma pneumoniae pneumonia (RMPP) and evaluate its safety. This study is an exploratory research, selecting 82 RMPP patients treated with levofloxacin who were admitted to the Department of Pediatric Respiratory Medicine at Weifang People's Hospital between November 2023 and December 2024 as the research subjects. Compared the blood routine and biochemical indicators before and after the application of levofloxacin, and observed the clinical efficacy and adverse reactions of levofloxacin. The average fever reduction time after the application of levofloxacin was (1.96 ± 1.52) days. After the application of levofloxacin, there was no change in white blood cell (WBC), neutrophil (N), platelet (PLT) and other parameters in the blood routine (P > 0.05). The lymphocyte count (L) has increased but remains within the normal range. There was no difference in alanine aminotransferase (ALT) before and after treatment, but aspartate aminotransferase (AST) decreased compared to before. Lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CKMB) decreased after medication (P < 0.05), while creatine kinase (CK) remained unchanged. Blood creatinine (CREA) and Blood urea (Urea) both decreased (P < 0.05), indicating no damage to liver and kidney function. There were a total of 9 adverse drug reactions related to levofloxacin, including 5 cases of rash, 2 cases of gastrointestinal reactions, 1 case of neurological reaction, and 1 case of lower limb pain. No other adverse reactions or sequelae were observed during the 12-month clinical follow-up. Levofloxacin has shown good efficacy in treating RMPP in children, with no serious adverse reactions detected in a short period of time.

Pentadecyl®, derived from Aurantiochytrium limacinum, is a triglyceride primarily composed of odd-numbered fatty acids such as pentadecanoic acid (C15). Pentadecyl® improves glucose tolerance in a mouse model of type II diabetes and promotes collagen production in human skin cells. However, its effects on kidney failure and chronic kidney disease (CKD) remain unexplored. The present study examined the effects of continuous Pentadecyl® administration on renal dysfunction in 5/6-nephrectomized mice (5/6Nx mice), a well-established model of CKD. Pentadecyl® (0.2 g/l) was administered orally via a suspension in drinking water for 8 weeks. Although survival analysis using the log-rank test revealed no significant differences, a significant improvement in body weight gain was observed in 5/6Nx mice treated with Pentadecyl® compared with that in untreated controls, despite similar food and water intake. Renal function was assessed by measuring blood urea nitrogen (BUN) and serum creatinine (CRE) levels, both of which were significantly elevated in 5/6Nx mice. Notably, Pentadecyl® administration attenuated the increase in BUN and CRE levels. Histopathological analysis through hematoxylin and eosin staining revealed characteristic changes in the kidneys of 5/6Nx mice, including glomerular hypertrophy and tubular dilation. There was no significant difference in the mean glomerular and tubular areas between Pentadecyl®-treated mice and 5/6Nx mice. Nonetheless, distribution analyses descriptively showed fewer enlarged tubular profiles. These findings suggest that Pentadecyl® exerts protective effects against renal dysfunction in CKD, potentially contributing to the prevention of uremic complications.

Early diagnosis of chronic kidney disease (CKD) remains a major clinical challenge. Periostin (POST) and kidney injury molecule-1 (KIM-1) have been proposed as biomarkers of tubular injury and fibrosis. This study aimed to evaluate their utility as markers associated with CKD stage and their associations with renal function and proteinuria in children. Twenty-three children with CKD stages I-IV and 23 healthy controls were enrolled. Serum and urinary POST and KIM-1 were measured together with creatinine (CR), cystatin C (CysC), proteinuria, albuminuria, and urinary α1- and β2-microglobulin. Patients were classified as early stage (ES; CKD I-II) or late stage (LS; CKD III-IV). Serum and urinary POST and KIM-1, uPOST/CR, uKIM-1/CR, fractional excretion indices (FePOST, FeKIM-1), and UPCR were higher in CKD patients than in controls. Absolute biomarker concentrations did not differ between ES and LS and were not associated with eGFR, UPCR, UACR, or tubular protein excretion. In contrast, uPOST/CR, uKIM-1/CR, FePOST, and FeKIM-1 increased with CKD stage, were higher in LS than ES, correlated positively with CysC, and inversely with eGFR. FePOST and FeKIM-1 also correlated strongly with tubular protein markers. The FePOST/FeKIM-1 ratio was elevated in ES patients compared with controls and remained stable across CKD stages. Fractional excretion of POST and KIM-1 is associated with CKD stage and reflects ongoing tubular injury in children. The FePOST/FeKIM-1 ratio may represent a sensitive marker of early CKD.

Construction of BSA-CuNCs@UiO-66 nanoprobe based on MOF confinement effect and its ultrasensitive fluorescence sensing for creatinine.

5-Bromocytidine protects against hyperuricemia-induced renal injury by suppressing TLR4/NF-κB-mediated inflammation.

To investigate the protective effects of carbon quantum dots (CQDs) derived from Allium macrostemon (Xiebai) administered orally or via intraperitoneal injection in a mouse model of cisplatin-induced acute kidney injury (AKI) and explore the underlying mechanisms. Male C57BL/6 mice were randomly divided into control group, AKI model group, intraperitoneal injection group, and oral administration group (n=6). In all but the control group, the mice received a single intraperitoneal injection of cisplatin (20 mg/kg) on day 3 to induce AKI; intraperitoneal injections of Xiebai-derived CQDs (0.25 mL/day) were administered on a daily basis for 5 consecutive days, and oral CQD solution was given at the dose of 1 mL/day. On day 6, blood samples were collected to measure serum creatinine (CRE) and blood urea nitrogen (BUN). HE staining and transmission electron microscopy (TEM) were used to evaluate kidney tissue structure, mitochondrial morphology, and podocyte injury. Expression levels of renal injury markers (KIM-1 and NGAL) and inflammatory cytokines (IL-6, TNF‑α, and IL-1β) were determined with with RT-qPCR and Western blotting. Compared with those in the control group, AKI mice exhibited significant weight loss, renal enlargement, increased kidney-to-body weight ratio, and elevated serum CRE and BUN levels. In both Xiebai CQDs treatment groups, kidney/body weight ratios and serum CRE and BUN levels were reduced and the expression levels of KIM-1, NGAL, and inflammatory cytokines were lowered significantly. Histological and ultrastructural analyses revealed more intact renal architecture, reduced inflammatory infiltration, restored mitochondrial morphology, and alleviated podocyte foot process fusion and basement membrane thickening in the two treatment groups, particularly in the intraperitoneal injection group. Intraperitoneal administration of Xiebai-derived CQDs effectively attenuates cisplatin-induced AKI in mice, improves renal function, suppresses inflammatory responses, and repairs mitochondrial damage, thus offering better renal targeting and protective effects for AKI prevention and treatment.

This study evaluated the effects of dietary protein levels during late gestation on nutrient digestibility, plasma amino acid profiles in jennies, and donkey foal growth performance. Twenty-four pregnant jennies were randomly assigned to one of three diets with different crude protein (CP) contents during late gestation: 12.48% (HP), 11.52% (MP), and 10.54% (LP) on a dry matter basis. All animals received the same diet immediately after parturition for a duration of 30 days. During the trial, two digestion experiments were conducted, blood samples were collected at 28 and 7 days prepartum, and weekly weight measurements of jennies and foals were recorded. The results indicated that the dietary protein level did not significantly affect feed intake in late gestation. However, apparent nutrient digestibility of dry matter (DM), neutral detergent fiber (NDF), acid detergent fiber (ADF), crude protein (CP), and ether extract (EE), and calcium (Ca) and phosphorus (P) was generally higher in the MP and LP groups than in the HP group, with MP showing the most consistent improvements across nutrients and timepoints (p < 0.05). Although the HP diet increased plasma concentrations of certain amino acids, including glutamic acid (Glu), valine (Val), methionine (Met), leucine (Leu), essential amino acids (EAAs), functional amino acids (FAAs), and branched chain amino acids (BCAAs), and elevated serum levels of glucose (GLU), blood urea nitrogen (BUN), and creatinine (CRE), it failed to improve postpartum weight recovery in jennies, highlighting that weight dynamics during this period are governed by factors beyond dietary protein content alone. Specifically, the LP group exhibited significantly higher cumulative postpartum weight loss over weeks 1-4 than the HP group (p = 0.004). Regarding offspring performance, both HP and MP diets improved foal birth weight, weekly body weight up to 4 weeks, average daily gain, and body height compared to the LP group (p < 0.05), with no significant differences observed between the HP and MP groups. In conclusion, for jennies under the current confined feeding system, a late-gestation diet containing 11.52% CP was adequate to support higher nutrient digestibility in the jennies and better growth performance in their foals, compared to a lower protein level (10.54% CP). However, increasing the dietary CP to 12.48% provided no additional benefits in nutrient utilization or overall productivity.

BackgroundSevere Fever with Thrombocytopenia Syndrome (SFTS) is characterized by high mortality and rapid progression, necessitating accurate early prognosis to optimize supportive care. However, current predictive tools often lack interpretability, require sophisticated tests unavailable in resource-limited areas, or suffer from poor generalizability. This study aimed to develop an interpretable, parsimonious, and deployable machine learning model for early mortality prediction in SFTS.MethodsWe analyzed data from 834 SFTS patients across three medical centers in Anhui, China. A LightGBM model was developed using a derivation cohort (n = 571) and validated on internal (n = 143) and two independent external cohorts (n = 80 and n = 183). Model interpretability was enhanced using SHapley Additive exPlanations (SHAP), and a web-based calculator was deployed for clinical use.ResultsThe LightGBM model identified six routine clinical parameters—Age, Lactate Dehydrogenase (LDH), Activated Partial Thromboplastin Time (APTT), Uric Acid (UA), Creatinine (CRE), and Body Temperature—as the most influential predictors. Integrating these features, the model achieved robust discrimination with an Area Under the Curve (AUC) of 0.960 in the training set and 0.938 in the internal validation set. Crucially, it maintained strong performance in two independent external validation cohorts (AUC 0.871 and 0.877). SHAP analysis revealed that Age and LDH were the strongest risk factors, while Temperature exhibited a non-linear relationship with mortality risk.ConclusionWe developed and validated a high-performance, interpretable ML model for SFTS prognosis relying on only six readily available parameters. By deploying this parsimonious model as an online calculator, we provide a practical decision-support tool to facilitate early risk stratification and timely intervention, particularly in resource-limited settings.

Gilts have a lower capacity for voluntary feed intake and body reserves than multiparous sows, which limits their ability to cope with the needs of gestation and lactation. In this study, a nutritional supplement was formulated to support gilts during the peripartum period. Both control (C, n = 64) and treatment (T, n = 63) groups received standard commercial diets. Group T received 300gr of supplement per gilt and day for the last 35 days of gestation until the fifth day of lactation. This supplement contained calcium (Ca; 4.1%), sodium (Na; 4.0%), lysine (Lys; 1.96%), methionine (Met; 1.32%), vitamin B12 (0.3 mg/kg), choline chloride (600 mg/kg), betaine (475 mg/kg), and L-carnitine (500 mg/kg). Supplementation significantly reduced (p < 0.050) stillbirth rate, neonatal diarrhea, postpartum hypophagia, and both β-hydroxybutyrate (BHBA) and creatinine (CREA) concentrations (effect sizes: 0.240-0.993). Also, supplementation significantly increased (p < 0.050) piglet weight at birth and at 15 days of lactation and maternal backfat thickness at 26 days of lactation (effect sizes: 0.491-0.719). The concentrations of BHBA and CREA showed significant and negative associations with several productive parameters (p < 0.05); the strength of the associations was low-medium. Targeted peripartum supplementation represents a feasible nutritional strategy for commercial herds characterized by large litter sizes and limited voluntary feed intake capacity.

Curcumin alleviates dry/heat stress-induced acute kidney injury by reducing the formation of neutrophil extracellular traps in rats.

Lactate dehydrogenase (LDH) is widely used as a nonspecific marker of tissue damage and cellular turnover and has been associated with metabolic and inflammatory processes, but its relationship with automated monitoring data and blood biochemical indicators in early-lactation dairy cows is still not well described. The aim of this study was to evaluate associations between LDH activity, blood biochemical parameters, and automated monitoring indicators in early-lactation Holstein cows. A total of 91 clinically healthy cows were classified into two groups according to LDH activity: Group 1 (LDH &lt; 1364 U/L; n = 53) and Group 2 (LDH ≥ 1364 U/L; n = 38). Blood samples were collected once per cow during early lactation, whereas automated monitoring parameters were continuously recorded and daily averages corresponding to the sampling day were used for analysis. Cows with higher LDH activity had significantly higher aspartate aminotransferase (AST) activity and moderate increases in albumin (ALB), creatinine (CREA), gamma-glutamyl transferase (GGT), calcium (Ca), phosphorus (PHOS), and iron (Fe). Correlation analysis showed a strong positive association between LDH and AST (r = 0.799, p &lt; 0.001), while moderate positive correlations were observed with ALB, alanine aminotransferase (ALT), CREA, Ca, GGT, Fe, and PHOS. Receiver operating characteristic (ROC) analysis showed the best discrimination ability for AST, while CREA, ALB, Fe, PHOS, Ca, and GGT showed moderate classification performance. Automated monitoring parameters did not differ significantly between groups; however, cows with higher LDH activity tended to show lower rumination time together with higher milk electrical conductivity, higher milk yield, higher fat-to-protein ratio (FPR), and higher somatic cell count (SCC). Overall, the results indicate that LDH is more closely related to systemic biochemical variation than to immediate changes in production or behavioral indicators, and support the use of biochemical markers together with automated monitoring data when evaluating physiological adaptation during early lactation.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging acute infectious disease. Current studies have mostly focused on its clinical characteristics and epidemiology, while research related to rhabdomyolysis (RM) remains limited. This study aimed to explore the relationship between RM and the prognosis of SFTS patients based on dynamic clinical data, identify dynamic associations with RM in SFTS patients, and provide a reference for early clinical identification and intervention. A retrospective analysis was performed on the clinical data of 537 SFTS patients admitted to Yijishan Hospital of Wannan Medical College and the First Affiliated Hospital of Nanjing Medical University. The patients were divided into the non-survivor group (N = 95) and survivor group (N = 442); additionally, they were categorized into the RM group (N = 74) and non-RM group (N = 463). Epidemiological data, clinical symptoms, and dynamic laboratory findings during the disease course were statistically analyzed. To screen associations with RM, univariate logistic regression analysis was conducted on laboratory findings obtained within 14 days of the disease course. Receiver operating characteristic (ROC) curves were further used to evaluate the predictive value of these associations with RM. Among the 537 SFTS patients, 95 (17.7%) were in the non-survivor group, of which 40 (42.10%) had concurrent RM; 442 (82.3%) were in the survivor group, of which 34 (7.69%) had RM. The difference in RM incidence between the two groups was statistically significant (p < 0.001). The mortality rate of the RM group (54.10%) was significantly higher than that of the non-RM group (11.90%) (p < 0.001). Dynamic laboratory findings indicated that the number of differential laboratory indicators in SFTS patients began to increase from day 5 of the disease course, with the most significant changes being observed between days 7-10. Dynamic univariate logistic analysis revealed that aspartate aminotransferase (AST), hematocrit (HCT), chloride (Cl), and blood urea nitrogen (BUN) were early associations with RM during the initial phase (days 1-4); additional associations including alanine aminotransferase (ALT), amylase (AMY), activated partial thromboplastin time (APTT), platelets (PLT), red blood cells (RBC), and thrombin time (TT) emerged during the progressive phase (days 5-7); associations during the multiple organ dysfunction (MOD) phase (days 8-10) included AST, creatinine (CR), d-dimer (D-D), lactate dehydrogenase (LDH), AMY, APTT, BUN, calcium (Ca), potassium (K), TT, monocytes (MONO), and international normalized ratio (INR); during the remission phase (days 11-14), associations were APTT, creatine kinase-MB (CKMB), CR, LDH, neutrophils (Neut), TT, white blood cells (WBC), AST, C-reactive protein (CRP), and K levels. ROC curve analysis showed that AST and BUN on day 3, and HCT and Cl on day 4 of the disease course had good predictive value for RM in SFTS patients. SFTS patients with RM have a high mortality rate, and the occurrence of RM is closely related to patient prognosis. The associations with RM in SFTS patients change dynamically with the disease course: the progressive phase is the critical period for rhabdomyolysis onset, and the MOD phase is the most life-threatening stage. AST, BUN, HCT, and Cl levels can be used as biomarkers for the early identification of RM in SFTS patients. Clinical stratified monitoring based on their high sensitivity and specificity is feasible, and these indicators are suitable for primary care promotion due to their low routine detection cost and fast turnaround time.

Objective To evaluate whether serum Gasdermin D (GSDMD) levels are associated with diabetic kidney disease (DKD) and renal function impairment, and to assess its potential diagnostic value. Methods This cross-sectional observational study included 111 patients with DKD, 100 patients with non-diabetic kidney diseases, and 135 healthy controls. Serum GSDMD levels were measured using a chemiluminescence assay. Associations between GSDMD and clinical parameters were analyzed using Spearman correlation and binary logistic regression. Receiver operating characteristic (ROC) curves were constructed to evaluate diagnostic performance. Results Serum GSDMD levels were significantly higher in patients with DKD than in healthy controls (P &amp;lt; 0.05). GSDMD levels were positively correlated with glucose (GLU), creatinine (CREA), blood urea nitrogen (BUN), and urinary albumin-to-creatinine ratio (UACR), and negatively correlated with estimated glomerular filtration rate (eGFR) (all P &amp;lt; 0.01). Multivariate logistic regression identified GSDMD as an independent factor associated with DKD. The area under the ROC curve (AUC) for GSDMD in identifying DKD was 0.847 (95% CI: 0.808–0.886), which increased to 0.933 (95% CI: 0.904–0.962) when combined with conventional indicators. Conclusion Serum GSDMD levels are significantly associated with diabetic kidney disease and renal dysfunction. These findings suggest that GSDMD may serve as a complementary biomarker for DKD assessment; however, longitudinal and multicenter studies are required to confirm its prognostic value and clinical applicability.

.SignificanceIn vivo optical imaging is crucial for studying disease mechanisms but is limited by light scattering and poor penetration in biological tissues. While tissue-clearing reagents (hydrophilic/hydrophobic) and bioluminescent probes improve imaging, achieving effective optical transparency in live tissues remains a challenge. This study builds on recent work using absorbing dyes (tartrazine and 4-aminoantipyrine) to enhance in vivo tissue clearing, aiming to optimize efficacy and biosafety.AimWe aimed to develop a mixed solution of tartrazine and 4-aminoantipyrine (4-AA) that improves optical transparency, accelerates clearing, and reduces toxicity compared to individual dyes, enabling safer and more efficient deep-tissue imaging in live animals.ApproachThe study employed a multi-pronged experimental approach: solution optimization involved testing varying ratios of tartrazine and 4-AA (5:1, 10:1) to characterize their optical properties through UV-Vis-NIR spectroscopy and refractive-index measurements, while simultaneously evaluating ex vivo skin-clearing efficacy; in vivo validation was conducted by applying the optimized gels to depilated mouse skin and systematically recording key parameters including transparency-onset time, maximum clearing duration, and light transmittance; concurrent biosafety assessments monitored critical health indicators such as animal survival rates, longitudinal weight changes, and liver/kidney function markers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (CREA)] during the post-treatment period.ResultsThe optimized mixed solutions (5:1 and 10:1 tartrazine:4-AA ratios) demonstrated superior clearing efficiency, achieving faster tissue transparency than tartrazine alone while matching the performance of 4-AA but with significantly reduced toxicity. Optical characterization revealed stable refractive indices () and strong absorption across visible/NIR wavelengths for all formulations. While 4-AA alone exhibited severe hepatorenal toxicity and 100% mortality (3/3 mice), the 5:1 mixed solution maintained efficacy with no mortality and only mild ALT/AST elevation. Transmittance measurements showed 4-AA gels achieved light transmission, whereas mixed gels reached due to tartrazine’s residual absorption in the red–NIR spectrum, suggesting an optimal balance between clearing performance and biosafety in the composite formulations.ConclusionsThe 5:1 tartrazine:4-AA cocktail optimally balances speed, clarity, and biosafety, advancing in vivo tissue-clearing technology. This strategy addresses key limitations of stand-alone dyes and expands potential applications in biomedical imaging, such as 3D tumor visualization and dynamic pathology studies. Future work should refine ratios for diverse tissues and integrate auxiliary agents (e.g., surfactants) to further enhance clearing.

Chronic kidney disease (CKD) is characterized by tubulointerstitial fibrosis and has a high prevalence, with limited clinical treatment options available. Saikosaponin D (SSD) is a major component of the traditional Chinese medicine compound Chaihuang Yishen Granules (CHYS) and exhibits favorable anti-fibrotic effects. However, its role and underlying mechanisms in renal fibrosis remain unclear. To elucidate the protective effects of SSD on CKD-induced renal fibrosis and investigate the underlying mechanism by which SSD alleviates renal fibrosis through regulating hexokinase-2 (HK2)-mediated Smad3 activation, CKD models were established using unilateral ureteral obstruction (UUO) and adenine (ADE) induction. Subsequently, SSD was administered via oral gavage as a therapeutic intervention to observe its protective effects against CKD-induced renal fibrosis. Mechanistically, invitro experiments involving HK2 overexpression and knockdown, as well as the use of SIS3 to inhibit Smad3 activation, evaluated the regulatory role of HK2 on glycolysis and Smad3. The results demonstrated that SSD treatment significantly improved the abnormal serum creatinine (CRE) and blood urea nitrogen (BUN) levels in CKD mice, alleviated renal pathological damage, and reduced the expression of fibrosis-related proteins (Col-I, FN, α-SMA). HK2 was found to promote glycolysis-related enzymes and Smad3 activation. Inhibition of Smad3 activation with 4 μM SIS3 significantly attenuated TGF-β-induced fibrosis in tubular cells but had no effect on HK2 expression or glycolysis. Direct suppression of LDHA-mediated lactate production using 25 mM oxamic acid sodium (OX) markedly reduced HK2-induced Smad3 activation and tubular cell fibrosis. This study reveals that SSD significantly alleviates CKD-induced renal fibrosis by inhibiting HK2-mediated Smad3 activation. Lactate, not only as the end product of HK2-driven glycolysis, but also acts as a signaling mediator in HK2-regulated Smad3 activation, facilitating its activation.

Third-generation cephalosporins are widely used for severe infections but carry thrombocythemia risks complicating therapeutic decisions. Current predictive tools lack accuracy and clinical interpretability. This study aimed to develop an interpretable machine learning (ML) model for thrombocythemia risk stratification during cephalosporin therapy. A retrospective cohort of 45,779 adults treated with third-generation cephalosporins (2019-2023) was analyzed. After exclusions (age <18, missing data, baseline platelet anomalies), 25,707 patients were included. Thrombocythemia was defined as platelet count >400×109/L within 30 days post-treatment. Predictors encompassed demographics, comorbidities, medications, and laboratory parameters. Data preprocessing included multiple imputation and stratified partitioning (70% training, 30% testing). Three ML algorithms (XGBoost, Random Forest, LightGBM) were evaluated using ROC-AUC, Brier score, and clinical utility metrics. SHAP analysis provided model interpretability. XGBoost demonstrated superior performance, achieving the highest test-set discrimination (AUC=0.858, 95% CI:0.814-0.902) and calibration (Brier score=0.0088). SHAP analysis identified Baseline platelet count (PLT), red blood cell count (RBC), creatinine (CRE), daily usage frequency, and sex as key drivers. PLT was the strongest predictor (SHAP range: -1.67 to +1.48), with lower PLT exerting protective effects. RBC and CRE ranked second and third in importance, showing nonlinear risk relationships. Key clinical interactions included amplified risk from malignancies (SHAP=-0.215) and protective effects of female sex (SHAP=-0.194). This interpretable ML framework enables precise thrombocythemia risk prediction during cephalosporin therapy, balancing algorithmic performance with clinical actionability.

High-dose methotrexate is widely used in chemotherapy for malignant tumors. This study explores the correlation between methotrexate (MTX) and 7-hydroxy methotrexate (7-OHMTX) concentrations and indicators of liver and kidney function while evaluating the predictive value of MTX and 7-OHMTX levels for delayed elimination. The authors collected 372 blood samples from 107 leukemia or lymphoma patients (45 adults and 62 children) treated with high-dose methotrexate. The free and total concentrations of MTX and 7-OHMTX were measured 48, 72, or 96 hours after chemotherapy administration. SPSS 27 software was used to analyze the Spearman correlation between concentration and liver and kidney indicators. The nonparametric Mann-Whitney U test was used to compare the Normal and Delayed groups. Receiver operating characteristic curve analysis identified the threshold for delayed elimination. The total 7-OHMTX concentration did not correlate with creatinine clearance (CCR) and creatinine (CR) in children. The free 7-OHMTX concentration showed a significant negative correlation with CCR (P < 0.01) and a positive correlation with CR (P < 0.01) in children and in subgroup A2 (7-12 years). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly negatively correlated with both total and free 7-OHMTX/MTX concentrations in children (P < 0.01). MTX and 7-OHMTX concentrations showed no correlation with CR, CCR, AST, or ALT in adult patients. Clinicians should closely monitor patients for signs of elimination delay when free 7-OHMTX concentrations exceed 0.081 μmol/L 48 hours or later. Incorporating free-concentration monitoring predicts hepatotoxicity and nephrotoxicity in children more accurately than total concentrations alone, facilitating timely clinical intervention and ensuring patient safety.

This study aimed to explore nutritional strategies for improving the reproductive performance and antioxidant capacity of female <italic>Macrobrachium rosenbergii</italic>, providing data support for the artificial breeding of this species. The commercial diet (CT, 36% protein, 7.9% fat) was used as the control group, with five experimental diets formulated by adding soybean lecithin (LE), arachidonic acid (AA), astaxanthin (AS), soybean lecithin+arachidonic acid+astaxanthin complex (LE+AA+AS), and compound vitamins and minerals (AM), respectively. These diets were fed to female <italic>M. rosenbergii</italic> for 8 weeks. After nutritional enrichment, the hepatopancreas index, gonadosomatic index, spawning rate, and relative egg weight of shrimp in different diet groups were compared, as well as the changes of hemolymph biochemical composition, antioxidant capacity, and gonad development-related gene expression level of broodstock. The results showed that: in terms of reproductive performance, the hepatopancreas index of female shrimp in AA, AS, and LE+AA+AS groups was significantly higher (<italic>P</italic>&lt;0.05), while serum creatinine (CREA) levels in AS group and LE+AA+AS group was significantly lower (<italic>P</italic>&lt;0.05). In addition to the LE group, the hemolymph alanine aminotransferase (ALT) content was significantly reduced in all additive group (<italic>P</italic>&lt;0.05), and the AA group exhibited significantly higher hemolymph albumin (ALB), triacylglycerol (TG), and Total cholesterol (TC) contents (<italic>P</italic>&lt;0.05). Expression levels of Cyclooxygenase (<italic>COX</italic>)<italic>,</italic> Croquetprotein (<italic>CRQ</italic>)<italic>,</italic> vitellogenin (<italic>VTG</italic>), and Pyrokinins (<italic>PK</italic>) genes were significantly up-regulated in the AS and LE+AA+AS groups (<italic>P</italic>&lt;0.05), and <italic>VTG</italic> expression was also significantly up-regulated in the AM group (<italic>P</italic>&lt;0.05). In terms of antioxidant capacity, the AS and LE+AA+AS groups showed an increase in ASA and iNOS activity in the hemolymph, and a significant increase in the expression of <italic>toll</italic>, <italic>Dorsal</italic>, <italic>Relish</italic>, and <italic>IMD</italic> genes in the hepatopancreas (<italic>P</italic>&lt;0.05). The results showed that astaxanthin had the strongest effect on promoting reproductive performance and antioxidant capacity in <italic>M. rosenbergii</italic> broodstock. Adding an appropriate amount of compound vitamins and minerals benefited yolk formation. Arachidonic acid, compound vitamins and minerals supported lipid nutrient reserve and mobilization of broodstock during breeding period, and arachidonic acid also exerting a better antioxidant effect.