Objective: To verify the inhibitory effect of a carbon monoxide hemoglobin-based oxygen carrier (CO-HBOC) on the fibrotic process in mice with idiopathic pulmonary fibrosis (IPF), clarify its efficacy difference compared with hemoglobin-based oxygen carriers (HBOCs), and elucidate its mechanism of action via proteomic analysis. Methods: CO-HBOC was prepared using gas loading technology. An IPF mouse model was established and the mice were randomly divided into a normal saline control group, an HBOC treatment group, and a CO-HBOC treatment group. The fibrotic area percentage was analyzed using Micro-CT; the degree of inflammatory infiltration and fibrosis in lung tissue was assessed by pathological section staining (e.g., HE and Masson staining); and differentially expressed proteins in lung tissue of IPF mice after CO-HBOC treatment were screened using proteomic technology. Results: Micro-CT results showed that the mean fibrotic area percentage in the CO-HBOC treatment group on day 21 was (8.89±0.98)%, which was better than that of the HBOC group (16.5±1.732)% and the normal saline group (30.75±6.45)% (P<0.05). HE and Masson staining results showed that the CO-HBOC group had reduced inflammatory cell infiltration and significantly decreased collagen fiber deposition in lung tissue, with a mean pathological score of 3.33±0.58, which was lower than that of the normal saline control group (8.33±1.53)(P<0.05); the mean collagen-positive area percentage was (3.33±1.53)%, significantly lower than that of the normal saline control group (14.00±3.61)% (P<0.05). Proteomic analysis identified 330 differentially expressed proteins, which were mainly enriched in inflammatory response regulatory pathways (such as the complement and coagulation cascades), and the expression changes of complement proteins may be the core target of CO-HBOC's anti-fibrotic effects. Conclusion: CO-HBOC can inhibit inflammatory responses and regulate fibrosis-related signaling pathways, there-by effectively inhibiting the fibrotic process in IPF mice, with superior efficacy to HBOC. Its mechanism of action involves the regulation of complement cascade-related signaling pathways and complement protein expression, providing an experimental and theoretical basis for targeted therapy of IPF.

Acute lung injury （ALI） is a life-threatening condition characterized by uncontrolled pulmonary inflammatory responses， presenting high morbidity and mortality rates that pose serious threats to patient health. The pathogenesis of ALI involves complex interactions among pathological mechanisms including immune-inflammatory responses， disruption of the alveolar-capillary barrier， mesenchymal stem cell dysfunction， metabolic disorders， ferroptosis， and alterations in the gut microbiota. The dysregulation of programmed cell death （PCD） has increasingly emerged as a research focus. PCD represents a genetically regulated autonomous process of cell death， crucial for maintaining the internal stability of organisms. Recent studies indicate that multiple PCD modes， including apoptosis， pyroptosis， necroptosis， autophagy， and ferroptosis， participate in the development and progression of ALI by mediating pathological processes such as alveolar epithelial cell injury and vascular endothelial barrier disruption. Current therapeutic approaches for ALI encompass lung-protective ventilation， body fluid management， mesenchymal stem cell therapy， and pharmacological interventions. While these measures may alleviate clinical symptoms， they remain unable to reverse the pathological progression of lung injury. Traditional Chinese medicine （TCM） possesses the unique advantages of a holistic perspective and syndrome differentiation-based treatment， achieving breakthrough progress in targeted PCD intervention for ALI. It can mitigate pulmonary tissue injury by suppressing inflammatory responses， regulating immune function， and improving coagulation disorders， thereby delaying the onset and progression of ALI. This paper delves into the molecular mechanisms of PCD in ALI， systematically reviewing the effects of TCM extracts， active constituents （terpenoids， saponins， flavonoids， and phenols）， and compound formulas （e.g.， Qingjie Huagong prescription， Maxing Kugan Tang， and Yifei Jianpi prescription） in improving pulmonary epithelial cell function and mitigating lung injury by modulating PCD pathways. This review aims to provide theoretical underpinnings and novel directions for drug development in the clinical prevention and treatment of ALI.

Acute lung injury （ALI） is a life-threatening condition characterized by uncontrolled pulmonary inflammatory responses， presenting high morbidity and mortality rates that pose serious threats to patient health. The pathogenesis of ALI involves complex interactions among pathological mechanisms including immune-inflammatory responses， disruption of the alveolar-capillary barrier， mesenchymal stem cell dysfunction， metabolic disorders， ferroptosis， and alterations in the gut microbiota. The dysregulation of programmed cell death （PCD） has increasingly emerged as a research focus. PCD represents a genetically regulated autonomous process of cell death， crucial for maintaining the internal stability of organisms. Recent studies indicate that multiple PCD modes， including apoptosis， pyroptosis， necroptosis， autophagy， and ferroptosis， participate in the development and progression of ALI by mediating pathological processes such as alveolar epithelial cell injury and vascular endothelial barrier disruption. Current therapeutic approaches for ALI encompass lung-protective ventilation， body fluid management， mesenchymal stem cell therapy， and pharmacological interventions. While these measures may alleviate clinical symptoms， they remain unable to reverse the pathological progression of lung injury. Traditional Chinese medicine （TCM） possesses the unique advantages of a holistic perspective and syndrome differentiation-based treatment， achieving breakthrough progress in targeted PCD intervention for ALI. It can mitigate pulmonary tissue injury by suppressing inflammatory responses， regulating immune function， and improving coagulation disorders， thereby delaying the onset and progression of ALI. This paper delves into the molecular mechanisms of PCD in ALI， systematically reviewing the effects of TCM extracts， active constituents （terpenoids， saponins， flavonoids， and phenols）， and compound formulas （e.g.， Qingjie Huagong prescription， Maxing Kugan Tang， and Yifei Jianpi prescription） in improving pulmonary epithelial cell function and mitigating lung injury by modulating PCD pathways. This review aims to provide theoretical underpinnings and novel directions for drug development in the clinical prevention and treatment of ALI.

Malignant tumors represent a major global public health challenge,necessitating urgent innovation in diagnostic and therapeutic strategies.Lactate,a key metabolic product of tumor cell glycolysis,functions not merely as an energy metabolite but also as a signaling molecule to regulate malignant progression.Lactate mediates intercellular metabolite distribution through monocarboxylate transporter(MCT)-driven lactate shuttling and regulates epigenetics via histone lactylation.This integration establishes interconnected networks of energy,amino acid,and lipid metabolism that enhance tumor metabolic plasticity.In immune regulation,lactate induces a shift of T cells toward immunosuppressive phenotypes,impedes CD8+T cell memory differentiation,and attenuates cytotoxicity.Simultaneously,lactate not only reduces the immune efficacy of natural killer(NK)cells but also triggers apoptosis by inducing mitochondrial dysfunction,creating an immune-privileged niche for metastatic sites.Furthermore,elevated lactate levels activate multiple signaling pathways to recruit macrophages and drive their polarization toward the M2 phenotype,fostering an immunosuppressive microenvironment.Current therapeutic strategies target key aspects of lactate metabolism.Inhibiting lactate synthesis reduces lactate accumulation in tumor microenvironment(TME),countering the tumor's metabolic advantage and diminishing its role in driving metabolic reprogramming.Additionally,promoting the decomposition of lactate represents a promising new direction.Novel agents employing bioenzymes or biomimetic catalytic systems enhance local lactate clearance,alleviating the immunosuppressive effects of the acidic TME.This review comprehensively outlined the lactate-mediated regulatory network,aiming to provide systematic research directions and translational insights for developing more effective anti-tumor therapies.

Objective: To evaluate the effect of bioactive peptides combined with probiotics on serum uric acid (SUA) in patients with hyperuricemia (HUA), so as to provide the evidence for prevention and treatment of HUA. Methods: The patients with HUA aged 18 to 65 years were selected and randomly divided into an intervention group and a control group. The patients in the intervention group received bioactive peptides combined with probiotics for 28 days at a dose of 3 g/d, while the patients in the control group received an equal dose of placebos. Demographic information, body mass index (BMI), blood pressure and blood lipid were collected through questionnaire surveys, physical examination and laboratory tests. SUA levels were detected before and after 14 days and 28 days of interventions. The differences of SUA levels between the two groups were compared using generalized estimation equation. Results: Totally 108 patients with HUA were recruited, including 54 patients in the intervention group and 53 patients in the control group (1 dropout). Before interventions, there were no statistically significant differences in gender, age, course of HUA, exercise duration, frequency of alcohol consumption, frequency of meat broth consumption, BMI, prevalence of hypertension and prevalence of dyslipidemia between the two groups (all P>0.05). After 14 days of interventions, the SUA levels of the patients in the intervention group decreased by 3.00 μmol/L, while those in the control group increased by 7.00 μmol/L. After 28 days of interventions, the SUA levels of the patients in the intervention group and the control group decreased by 26.00 μmol/L and 16.00 μmol/L, respectively. However, there was no statistically significant interaction between the intervention time and group (both P>0.05). Subgroup analysis showed that after 28 days of interventions, the decrease in SUA levels in the patients aged 55 years and older and without hypertension in the intervention group was greater than those in the control group (both P<0.05). Conclusions Bioactive peptides combined with probiotics showed no significant difference in reducing SUA levels in patients with HUA compared to the control group. The effect was more significant for patients aged 55 years and older and without hypertension.

Malignant tumors represent a major global public health challenge,necessitating urgent innovation in diagnostic and therapeutic strategies.Lactate,a key metabolic product of tumor cell glycolysis,functions not merely as an energy metabolite but also as a signaling molecule to regulate malignant progression.Lactate mediates intercellular metabolite distribution through monocarboxylate transporter(MCT)-driven lactate shuttling and regulates epigenetics via histone lactylation.This integration establishes interconnected networks of energy,amino acid,and lipid metabolism that enhance tumor metabolic plasticity.In immune regulation,lactate induces a shift of T cells toward immunosuppressive phenotypes,impedes CD8+T cell memory differentiation,and attenuates cytotoxicity.Simultaneously,lactate not only reduces the immune efficacy of natural killer(NK)cells but also triggers apoptosis by inducing mitochondrial dysfunction,creating an immune-privileged niche for metastatic sites.Furthermore,elevated lactate levels activate multiple signaling pathways to recruit macrophages and drive their polarization toward the M2 phenotype,fostering an immunosuppressive microenvironment.Current therapeutic strategies target key aspects of lactate metabolism.Inhibiting lactate synthesis reduces lactate accumulation in tumor microenvironment(TME),countering the tumor's metabolic advantage and diminishing its role in driving metabolic reprogramming.Additionally,promoting the decomposition of lactate represents a promising new direction.Novel agents employing bioenzymes or biomimetic catalytic systems enhance local lactate clearance,alleviating the immunosuppressive effects of the acidic TME.This review comprehensively outlined the lactate-mediated regulatory network,aiming to provide systematic research directions and translational insights for developing more effective anti-tumor therapies.

Objective:To explore the RH genotype for a female with RhD(-) blood type and its molecular basis. Methods:A 26-year-old female who had attended the outpatient clinic of the First Affiliated Hospital of Zhengzhou University in August 2019 was selected as the study subject. Peripheral blood samples were collected from the proband and her parents for Rh phenotyping with gel card method. PCR-sequence-based typing (PCR-SBT) and DNA sequencing were used to determine the RHD zygosity and RH genotype of the proband and her parents. Homology modeling of Rh proteins was performed with bioinformatic software, and protein structural alterations caused by the variant was simulated by molecular dynamics. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. 2023-KY-0870-003). Results:Serological tests showed that the proband and her father both had weakened e antigen of the Rh phenotype. PCR-SBT and DNA sequencing showed that the genotypes of the proband and her parents were dce/ dCE, dce/ DcE and dCE/ DcE, respectively. And the genotypes of the RHD and RHCE of the proband were RHD*01N.01/ RHD*01N.16, RHCE*01.01/RHCE*04, respectively. Protein simulation and molecular dynamics analysis revealed that the ce_16C variant resulted from RHCE* ce (c.48G>C) may alter the structure of intracellular and extracellular loops, mainly affecting the mobility of extracellular loops 2, 6 and intracellular loops 3, 4. Conclusion:Variant of the RHCE* ce allele c. 48G>C probably underlay the weakened e antigen in this proband.

Objective To investigate the potential active ingredients and the mechanism of Coreopsis tinctoria Nutt. in the prevention and treatment of hyperlipidemia. Methods Ultra-high performance liquid chromatography-Quadrupole-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap MS) was used to qualitatively analyze the fractions and blood components of flavones in Coreopsis tinctoria Nutt. The intersection targets of flavones in Coreopsis tinctoria Nutt. and hyperlipidemia were screened,and the protein-protein interaction network was constructed and analyzed by the STRING 12.0 database. Finally,the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for enrichment analysis. Results A total of 25 compounds were detected from the flavones in Coreopsis tinctoria Nutt.,and their structures were identified,including ten chalcones,nine flavanones,four flavonols,one aurone,and one biflavone. The analysis of blood components showed that marein,flavanomarein,okanin,isookanin and 5,7,3',5'-tetrahydroxyflavanone-7-O-β-D-glucopyranoside were the main components of the flavones in Coreopsis tinctoria Nutt. in blood. Network pharmacological GO and KEGG enrichment analysis showed that the flavones in Coreopsis tinctoria Nutt. may regulate phosphatidylinositol 3-kinase/protein kinase B,tumor necrosis factor,hypoxia-inducible factor-1 signaling pathway and other signaling pathways in the regulation and prevention of hyperlipidemia. Conclusion Coreopsis tinctoria Nutt. can prevent and treat hyperlipidemia,and the mechanism may be related to the five blood components of the flavones in Coreopsis tinctoria Nutt.,including marein,flavanomarein,okanin,isookanin and 5,7,3',5'-tetrahydroxyflavanone-7-O-β-D-glucopyranoside.

In recent years, the field of genetics has witnessed a burgeoning interest in the non-coding region, an area previously dubbed the"dark matter"of the genome. This once enigmatic domain is now progressively revealing its secrets, emerging as a rich terrain for genetic diagnosis and treatment. This editorial centers on diverse diagnostic analyses and intervention techniques associated with the non-coding region, delving into its significance in the etiology, diagnosis, and treatment of both monogenic and polygenic disorders within the nervous system. In doing so, it offers a comprehensive perspective for the exploration of genetic disorders in the nervous system.

OBJECTIVE To analyze the current situation and characteristics of clinical trials of nasal spray registration in China in the past 10 years, and to discuss the future development trend of nasal spray drugs in China, taking into account the current situation of international research. METHODS By accessing the State Drug Administration's drug clinical trial registration and information disclosure platform(http://www.chinadrugtrials.org.cn/index.html), collected information on clinical trials of nasal spray drugs in China from the open registration date(November 1, 2012) to March 29, 2023, in terms of clinical trial status, analyzed the status and characteristics of clinical trials of nasal sprays in terms of clinical trial status, indications, geographical distribution and trial phases, and trial design types by Microsoft Office Excel. RESULTS A total of 80 clinical trials of nasal sprays were conducted in China, of which 24 (30.0%) were phase I, 15 (18.8%) were phase II, 13(16.3%) were phase III, 3(3.8%) were phase IV, 17(21.3%) were bioequivalence trials, and 8(10.0%) were other(pharmacokinetic/pharmacodynamic studies). The status of clinical trials included 13(16.3%) in progress(not yet enrolled), 7(8.8%) in progress (enrollment completed), 15(18.8%) in progress (enrollment in progress), 44(55.0%) completed, and 1(1.3%) voluntarily terminated. There were 56 phase I-IV clinical trials, including 41(73.2%) parallel group trials, 14(25.0%) crossover design trials, and 1(1.8%) single-arm trial. A total of 65(81.3%) were chemicals, 7(8.8%) were biologics and 8(10.0%) were traditional Chinese medicine/natural drugs. A total of 15 indications were identified, which included allergic rhinitis, sedation, dry eye, paroxysmal supraventricular tachycardia, etc. CONCLUSION The research and development of nasal sprays in China is still at an early stage, but it keeps up with the international and independent innovation ability is being strengthened, and more new clinical research directions and strategies of nasal sprays should be explored in the future to help the development of nasal sprays and meet the needs of more patients.