To investigate the changes in peripheral blood immune cells before and after the onset of septic shock in patients with malignant tumors, and to analyze the relationship between these immune cells and patient prognosis.

The onset and progression of chronic heart failure （CHF） are closely associated with myocardial energy metabolism disorders， and this pathological process significantly affects patient prognosis. Traditional Chinese medicine （TCM）， grounded in time-based medical theories such as the correspondence between humans and nature and the theory of circadian flow of meridians （Ziwu Liuzhu）， exhibits intrinsic consistency with modern circadian rhythm theory， providing a unique theoretical framework for understanding and intervening in CHF from a temporal perspective. This article systematically explores the impact of circadian rhythms on energy metabolism and the potential mechanisms by which TCM active ingredients intervene in CHF through a review of relevant literature. It is found that various TCM active ingredients， including flavonoids （such as nobiletin）， alkaloids （such as berberine）， and polyphenols （such as resveratrol）， can improve mitochondrial function， promote fatty acid oxidation， enhance glucose uptake and utilization efficiency， maintain metabolic balance， and alleviate oxidative stress and inflammatory responses in myocardial cells by regulating the expression and rhythms of core circadian clock genes such as CLOCK， BMAL1， PER， and CRY. These actions thereby correct energy metabolism disorders and improve cardiac function. Further exploration of the interaction mechanisms between these components and the circadian rhythms holds promise for providing novel theoretical foundations and potential intervention strategies for the prevention and treatment of CHF.

Background Lead is a typical persistent environmental pollutant that can accumulate in bones for decades. During pregnancy, alterations in calcium metabolism promote the mobilization of bone lead, resulting in secondary exposure; however, the mechanisms by which pregnancy-associated bone lead mobilization affects maternal renal function remain unclear. Objective To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury. Methods Newly weaned female Wistar rats were randomly assigned to a control or a lead-exposed group administered either 0.05% sodium acetate or 0.05% lead acetate in drinking water. Following a 4-week lead exposure and a 4-week washout period, the females were co-housed with healthy age-matched males for mating. Rats were sacrificed at early (gestational day 3) and late (gestational day 17) pregnancystages, respectively. Renal histopathology was assessed using hematoxylin and eosin staining staining. Mitochondria-related indicators, including oxidative stress, inflammatory responses, and energy metabolism, were measured. Differential metabolites were identified using serum metabolomics. Results Renal injury in the lead-exposed pregnant rats progressed in a time-dependent manner, characterized by degeneration of proximal tubular epithelial cells, glomerular hyaline changes, and interstitial inflammatory cell infiltration. Repeated measures ANOVA indicated a significant interaction between the treatment factor (lead exposure) and the temporal factor (gestational stage) on renal injury (P<0.001). Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (P<0.05), accompanied by a reduction in superoxide dismutase (SOD) and reduced glutathione (GSH) activities (P<0.05); regarding inflammatory markers, levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were elevated (P<0.01), whereas interleukin-33 (IL-33) was decreased in the lead-exposed group (P<0.05); energy metabolism-related indicators, including adenosine triphosphate (ATP) level, Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, and mitochondrial respiratory chain complexes I, III, and V activities, were significantly reduced (P<0.05) in the lead-exposed gorup. The typical differential metabolite N-methylisoleucine, identified through serum metabolomics analysis, was negatively correlated with blood lead levels, kidney injury scores, and IL-1β, while positively correlated with catalase (CAT) activity and Ca²⁺-Mg²⁺-ATPase. Conclusions Mitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.

Objective To improve the analysis method of the blood components of Yinchenhao decoction （YCHD） in vivo and explore its anti-hepatocellular carcinoma mechanism. Methods Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MS） was used to collect and analyze blood samples from mice. The mice were given a single dose of YCHD with a concentration of 0.1 g/ml and a dose of 25 ml/kg, and then the samples were collected 2 h post–administration, which was to systematically study the chemical components of YCHD in vivo. Network pharmacological methods were used to screen the components and targets of YCHD, and the targets of hepatocellular carcinoma; The common targets of YCHD and hepatocellular carcinoma were identified for GO enrichment and KEGG enrichment. Molecular docking was performed on the main targets to verify the binding ability between the active ingredients and the core targets. The relative mRNA expression levels of serine/threonine-protein kinase（AKT1） and tumor protein p53（TP53） in liver tissues were analyzed via qPCR, including the following mouse groups: mice with concanavalin A（Con-A）-induced acute liver injury without preventive administration, mice with Con-A-induced acute liver injury that received 14 d preventive oral administration of YCHD, and untreated control mice. Results ①The active ingredients of YCHD in the blood were identified by retrieving the data from the in vitro component analysis. They were chrysophanol, herniarin, aloe-emodin, and monotropein. ②The mechanism of action of the blood components against hepatocellular carcinoma （HCC） was further analyzed using network pharmacological methods, and a total of 30 components of YCHD were screened for 213 targets and 215 HCC targets. ③There were 17 intersection targets between YCHD and hepatocellular carcinoma, including AKT1, TP53, receptor tyrosine-protein kinase erbB-2 （ERBB2）, myelocytomatosis oncogene （MYC）, interleukin-1β （IL-1β）, etc. The GO enrichment results indicated that these components were primarily involved in DNA replication，chromosome segregation，leukocyte mediated immunity，leukocyte cell-cell adhesion. The KEGG enrichment results demonstrated that these components were predominantly associated with diverse cancer pathways. Additionally, the results indicated involvement in the citrate cycle （TCA cycle）, pyruvate metabolism, and p53 signaling pathway, ect. ④The results of molecular docking showed that chrysophanol, herniarin, and aloe - emodin had strong binding abilities with AKT1, TP53, ERBB2, MYC, and IL-1β. ⑤The relative expression of AKT1 and TP53 mRNA was significantly higher in the modelling group than in the control group. The relative expression of AKT1 and TP53 mRNA was significantly lower in the drug administration group than in the modelling group. Conclusion There were 4 blood components in YCHD, among which chrysophanol, herniarin, and aloe-emodin may act on AKT1, TP53, ERBB2, MYC, IL-1β and then participated in the regulation of cancer signaling pathways and p53 signaling pathway to play a role in the treatment of HCC.

In this study， bibliometric methods were used to systematically investigate the name and origin， the evolution of prescription composition， dose evolution， origin and processing method， decoction method， ancient application， modified application， modern application and other information of Huoxiang Zhengqisan. After research， Huoxiang Zhengqisan， also known as Huoxiang Zhengqitang， was first recorded in Taiping Huimin Hejijufang. The original formula is composed of 41.3 g of Arecae Pericarpium， 41.3 g of Angelicae Dahuricae Radix， 41.3 g of Perilla frutescens（actually Perillae Folium）， 41.3 g of Poria， 82.6 g of Pinelliae Rhizoma， 82.6 g of Atractylodis Macrocephalae Rhizoma， 82.6 g of Citri Reticulatae Pericarpium（actually Citri Exocarpium Rubbum）， 82.6 g of Magnoliae Officinalis Cortex， 82.6 g of Platycodonis Radix， 123.9 g of Pogostemonis Herba， and 103.25 g of Glycyrrhizae Radix et Rhizoma. In this formula， Magnoliae Officinalis Cortex is processed according to the specifications for ginger-processed products， Glycyrrhizae Radix et Rhizoma is processed according to the specifications for stir-fried products， and other herbs are used in their raw products. The botanical sources of the herbs are consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The above herbs are ground into a fine powder with a particle size passing through a No. 5 sieve. For each dose， take 8.26 g of the powdered formula， add 300 mL of water， along with 3 g of Zingiberis Rhizoma Recens and 3 g of Jujubae Fructus， and decoct until reduced to 140 mL. The decoction should be administered hot， with three times daily. To induce sweating， the patient should be kept warm under a quilt， and an additional dose should be prepared and taken if needed. This formula is traditionally used to relieve the exterior and resolve dampness， regulate Qi and harmonize the middle， which is mainly used to treat a series of diseases of digestive and respiratory systems. However， potential adverse reactions， including allergies， purpura and disulfiram-like reactions， should be considered during clinical use. Huoxiang Zhengqisan features a rational composition， extensive clinical application， and strong potential for further research and development.

In this study， bibliometric methods were used to systematically investigate the name and origin， the evolution of prescription composition， dose evolution， origin and processing method， decoction method， ancient application， modified application， modern application and other information of Huoxiang Zhengqisan. After research， Huoxiang Zhengqisan， also known as Huoxiang Zhengqitang， was first recorded in Taiping Huimin Hejijufang. The original formula is composed of 41.3 g of Arecae Pericarpium， 41.3 g of Angelicae Dahuricae Radix， 41.3 g of Perilla frutescens（actually Perillae Folium）， 41.3 g of Poria， 82.6 g of Pinelliae Rhizoma， 82.6 g of Atractylodis Macrocephalae Rhizoma， 82.6 g of Citri Reticulatae Pericarpium（actually Citri Exocarpium Rubbum）， 82.6 g of Magnoliae Officinalis Cortex， 82.6 g of Platycodonis Radix， 123.9 g of Pogostemonis Herba， and 103.25 g of Glycyrrhizae Radix et Rhizoma. In this formula， Magnoliae Officinalis Cortex is processed according to the specifications for ginger-processed products， Glycyrrhizae Radix et Rhizoma is processed according to the specifications for stir-fried products， and other herbs are used in their raw products. The botanical sources of the herbs are consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The above herbs are ground into a fine powder with a particle size passing through a No. 5 sieve. For each dose， take 8.26 g of the powdered formula， add 300 mL of water， along with 3 g of Zingiberis Rhizoma Recens and 3 g of Jujubae Fructus， and decoct until reduced to 140 mL. The decoction should be administered hot， with three times daily. To induce sweating， the patient should be kept warm under a quilt， and an additional dose should be prepared and taken if needed. This formula is traditionally used to relieve the exterior and resolve dampness， regulate Qi and harmonize the middle， which is mainly used to treat a series of diseases of digestive and respiratory systems. However， potential adverse reactions， including allergies， purpura and disulfiram-like reactions， should be considered during clinical use. Huoxiang Zhengqisan features a rational composition， extensive clinical application， and strong potential for further research and development.

OBJECTIVE To analyze the clinical characteristics and influential factors of drug-induced liver injury （DILI） in children caused by intravenous azithromycin. METHODS Clinical data of 157 DILI pediatric cases caused by intravenous azithromycin， reported by the Hengshui Adverse Drug Reaction Monitoring Center from January 2015 to January 2025， were collected as the observation group. Clinical data of pediatric patients who received intravenous azithromycin but did not develop DILI during the same period at Hengshui People’s Hospital were collected in a 1∶1 ratio to serve as the control group. The clinical classification， severity and prognosis of DILI in pediatric patients from the observation group were analyzed. Univariate and multivariate Logistic regression analyses were used to screen the independent risk factors for DILI in children caused by intravenous azithromycin. RESULTS Among 157 DILI cases， 92 cases （58.60%） had hepatocellular injury-type， 51 cases （32.48%） had cholestatic-type， and 14 cases （8.92%） had mixed-type. DILI severity was grade 1 in 117 cases （74.52%）， grade 2 in 33 cases （21.02%）， and grade 3 in 7 cases （4.46%）. Liver function had all recovered after stopping medication and symptomatic treatment. Combined with acetaminophen [OR＝3.769， 95%CI （1.615， 8.235）， P＝0.021]， daily dose of azithromycin＞10 mg/kg [OR＝ 2.237， 95%CI （1.075， 4.655）， P＝0.034] were independent risk factors for DILI in children caused by intravenous azithromycin. CONCLUSIONS Hepatocellular injury-type and cholestatic-type are relatively common in children with DILI caused by intravenous azithromycin， with mild severity being predominant and showing a favorable prognosis. Combination with acetaminophen and daily dose＞10 mg/kg are independent risk factors for azithromycin-induced DILI in children.

A targeted metabolomics study was conducted on the bile acid profiles in the liver and feces of rats induced by a high-fat diet and intervened by ginsenoside Rb_1, along with the detection of FXR pathway gene expression in the liver, to explore and clarify its mechanism of action. The content of biochemical indicators in the serum were detected using an automatic biochemical analyzer. Hematoxylin and eosin(HE) staining and oil red O staining were used to detect pathological changes and lipid deposition in the liver. RT-PCR was used to detect the mRNA expression of FXR, small heterodimer partner(SHP), cholesterol 7 alpha-hydroxylase(CYP7A1), and sterol regulatory element-binding protein-1c(SREBP-1c) in the liver. Targeted bile acid metabolomics technology was employed to analyze changes in bile acid profiles in liver tissue and feces, and a correlation analysis was performed between key genes such as FXR, SHP, CYP7A1, SREBP-1c and differential bile acid metabolites. The results showed that ginsenoside Rb_1 significantly reduced the levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), and high-density lipoprotein cholesterol(HDL-C) in the serum, alleviated the large fat vacuoles and lipid deposition in the liver, increased the expression of FXR mRNA in the liver, and decreased the expression of SREBP-1c mRNA. The expression of CYP7A1 and SHP mRNA was increased, but the differences were not statistically significant. Targeted bile acid metabolomics showed that ginsenoside Rb_1 could restore the levels of 9 bile acids in the liver and 8 bile acids in the feces. Ginsenoside Rb_1 also increased the percentage of taurocholic acid(TCA) in the liver(56.78%) and the percentage of 12-ketolithocholic acid(12-KLCA) in the feces(26.10%). Pathway enrichment analysis revealed two pathways involved in bile acid metabolism: primary bile acid biosynthesis and taurine and hypotaurine metabolism. Correlation analysis showed that FXR, SHP, CYP7A1, and SREBP-1c were positively correlated with multiple differential bile acids. These results suggest that ginsenoside Rb_1 may intervene in lipid metabolism disorders induced by a high-fat diet by regulating the FXR pathway and modulating bile acid profiles in the liver and feces.
Animals ; Bile Acids and Salts/metabolism* ; Rats ; Ginsenosides/pharmacology* ; Male ; Receptors, Cytoplasmic and Nuclear/genetics* ; Liver/drug effects* ; Diet, High-Fat/adverse effects* ; Metabolomics ; Rats, Sprague-Dawley ; Feces/chemistry* ; Cholesterol 7-alpha-Hydroxylase/metabolism* ; Sterol Regulatory Element Binding Protein 1/genetics* ; Humans

Tegoprazan is a novel potassium-competitive acid blocker with long-lasting and potent acid-suppressing effects,showing favorable efficacy in many acid-related diseases.In eradicating Helicobacter pylori(Hp)infections,tegoprazan-based regimens are noninferior to proton pump inhibitor(PPI)regimens in terms of efficacy,and are well tolerated and safe.In this article,we review the pharmacological mechanism,clinical studies on Hp eradication regimens,and safety of tegoprazan to provide a reference for the selection of Hp e-radication regimens.

OBJECTIVES: To analyze the distribution of Y chromosome azoospermia factor (AZF) microdeletions and their association with testicular development in male pediatric patients with congenital reproductive system disorders, including hypospadias, cryptorchidism, and disorders of sex development (DSD). METHODS: A prospective cohort study was conducted on pediatric patients admitted to the Department of Urology of Shanghai Children's Hospital from November 2021 to December 2023. The observation group included boys with hypospadias, cryptorchidism, or DSD, while the control group comprised boys with phimosis, indirect inguinal hernia, or hydrocele. Blood samples were collected for AZF microdeletion analysis using multiplex PCR to detect 15 sequence-tagged sites. Testicular ultrasound was performed to record testicular position and volume. Propensity score matching (PSM) was used to balance the groups. After matching, testicular volume differences were assessed. Stratified analyses compared testicular volume among children with AZF microdeletions, the control group, and children without micro-deletions in observation group. RESULTS: A total of 493 children were enrolled (observation group: 463; control group: 30). No Y chromosome microdeletions were detected in the control group. Four boys in the observation group had AZF microdeletions: one with cryptorchidism (AZFc+AZFd), one with isolated hypospadias (AZFc), and two with DSD (one with AZFb+AZFc+AZFd and one with AZFa). Ultrasonography measured 888 testicles. After PSM, testicular volume was significantly smaller in the observation group than in the control group (P<0.01). Stratified analysis revealed that among children under 9 years, those with AZF microdeletions tended to be older but had smaller testicular volumes compared to the control group and those without microdeletions in the observation group, although differences were not statistically significant (all P>0.05). Among children over 9 years, ages were comparable, but children with AZF microdeletions had smaller testicular volumes than the other two groups (statistical analysis was not performed due to small sample size). CONCLUSIONS The prevalence of Y chromosome microdeletions is higher in male children with congenital reproductive system disorders compared to the general population, particularly in those with DSD. Hypospadias, cryptorchidism, DSD, and AZF microdeletions may be associated with delayed testicular development in these children.