Objective To explore the impact of national volume-based procurement policies on the use of medicines in treatment of benign prostatic hyperplasia （BPH） and provide data support for the rational clinical use of medicines in BPH treatment. Methods Data on the use of BPH treatment medications from 2019 to 2023 were extracted from the Chinese Medicine Economic Information Network （CMEI）, covering 892 hospitals （including 645 tertiary hospitals and 247 secondary hospitals）. The changes in various indicators, including the consumption sum, Defined daily doses （DDDs）, Defined daily dose cost （DDDc）, and the ranking ratio （B/A） of these drugs were analyzed and compared. Results From 2019 to 2023, due to the influence of relevant policies, the overall consumption sums of medicines used in the sample hospitals in BPH treatment showed a trend of decreasing first and then rising steadily. The DDDs showed an overall upward trend, while the DDDc demonstrated a gradual decline. Tamsulosin and finasteride consistently ranked first and second in DDDs. The B/A value for tamsulosin was significantly higher than that of other BPH treatment medications. Conclusion The implementation of national centralized drug volume-based procurement policies and other policies from 2019 to 2023 had effectively reduced the economic burden of patients with benign prostatic hyperplasia. Tamsulosin and finasteride, which had the highest B/A in the two categories of α-blockers and 5α-reductase inhibitors, dominated the market for BPH treatment. The clinical use of BPH treatment medications was relatively rational.

AIM: To investigate the relationship between the levels of interleukin-6(IL-6)and IL-2 in aqueous humor and the severity of optic nerve injury in patients with primary open-angle glaucoma(POAG), and to construct a decision tree model for the severity of optic nerve injury in POAG patients.METHODS: A prospective study was conducted on 107 patients(107 eyes)with POAG who were admitted to the hospital from May 2021 to October 2023. According to the mean defect(MD)value, the degree of optic nerve injury was judged and divided into three groups: mild, moderate and severe. The general data, IL-6 and IL-2 levels in aqueous humor of patients with different severity of optic nerve injury were compared, and the correlation between the levels of IL-6 and IL-2 in aqueous humor and the severity of optic nerve injury in POAG patients was analyzed. Multivariate Logistic regression analysis was used to test the influencing factors of the severity of optic nerve injury in POAG patients, and the decision tree model was constructed based on influencing factors.RESULTS: The proportion of patients with hypertension, intraocular pressure and binocular intraocular pressure difference in the severe group was higher than that in the mild and moderate groups, and the levels of IL-6 and IL-2 in the aqueous humor were significantly lower than those in the mild and moderate groups(all P<0.05). The levels of IL-6 and IL-2 in aqueous humor of POAG patients were negatively correlated with the severity of optic nerve injury(r=-0.361, -0.358, all P<0.001). Hypertension, intraocular pressure, binocular intraocular pressure difference, IL-6 and IL-2 levels in aqueous humor were independent factors affecting the degree of optic nerve injury in POAG patients(all P<0.05). Based on the above factors, a decision tree model was constructed, and three explanatory variables of IL-6, IL-2 levels in aqueous humor and hypertension were screened out. Among them, IL-2 level in aqueous humor was the most important root node variable and the most important predictor. The AUC of the decision tree model was 0.710(95% CI: 0.599-0.820, P=0.001), the sensitivity was 0.581, the specificity was 0.737, and the Youden index was 0.318, with a high predictive value.CONCLUSION: The levels of IL-6 and IL-2 in aqueous humor were significantly correlated with the severity of optic nerve injury in POAG patients. The decision tree model based on hypertension, intraocular pressure, binocular intraocular pressure difference, IL-6 and IL-2 levels in aqueous humor has a high evaluation value for the severity of optic nerve injury in POAG patients.

AIM: To investigate the relationship between the levels of interleukin-6(IL-6)and IL-2 in aqueous humor and the severity of optic nerve injury in patients with primary open-angle glaucoma(POAG), and to construct a decision tree model for the severity of optic nerve injury in POAG patients.METHODS: A prospective study was conducted on 107 patients(107 eyes)with POAG who were admitted to the hospital from May 2021 to October 2023. According to the mean defect(MD)value, the degree of optic nerve injury was judged and divided into three groups: mild, moderate and severe. The general data, IL-6 and IL-2 levels in aqueous humor of patients with different severity of optic nerve injury were compared, and the correlation between the levels of IL-6 and IL-2 in aqueous humor and the severity of optic nerve injury in POAG patients was analyzed. Multivariate Logistic regression analysis was used to test the influencing factors of the severity of optic nerve injury in POAG patients, and the decision tree model was constructed based on influencing factors.RESULTS: The proportion of patients with hypertension, intraocular pressure and binocular intraocular pressure difference in the severe group was higher than that in the mild and moderate groups, and the levels of IL-6 and IL-2 in the aqueous humor were significantly lower than those in the mild and moderate groups(all P<0.05). The levels of IL-6 and IL-2 in aqueous humor of POAG patients were negatively correlated with the severity of optic nerve injury(r=-0.361, -0.358, all P<0.001). Hypertension, intraocular pressure, binocular intraocular pressure difference, IL-6 and IL-2 levels in aqueous humor were independent factors affecting the degree of optic nerve injury in POAG patients(all P<0.05). Based on the above factors, a decision tree model was constructed, and three explanatory variables of IL-6, IL-2 levels in aqueous humor and hypertension were screened out. Among them, IL-2 level in aqueous humor was the most important root node variable and the most important predictor. The AUC of the decision tree model was 0.710(95% CI: 0.599-0.820, P=0.001), the sensitivity was 0.581, the specificity was 0.737, and the Youden index was 0.318, with a high predictive value.CONCLUSION: The levels of IL-6 and IL-2 in aqueous humor were significantly correlated with the severity of optic nerve injury in POAG patients. The decision tree model based on hypertension, intraocular pressure, binocular intraocular pressure difference, IL-6 and IL-2 levels in aqueous humor has a high evaluation value for the severity of optic nerve injury in POAG patients.

ObjectiveTo investigate the possible mechanism by which Zhiqiao Gancao Decoction （枳壳甘草汤， ZGD） delays intervertebral disc degeneration （IDD） based on the Hippo-yes-associated protein （YAP）/transcriptional co-activator with PDZ-binding motif （TAZ） signaling pathway. MethodsA total of 50 SD rats were randomly divided into sham surgery group， model group， low-dose ZGD group， high-dose ZGD group， and high-dose ZGD + inhibitor group， with 10 rats in each group. In the sham surgery group， the rats were pierced in the skin and muscle at the Co6/7/8 segments of the tail with a 21G needle （depth approximately 2 mm） without damaging the intervertebral disc. In the other groups， rats were injected with a 21G needle at the Co6/7/8 segments of the tail to establish an IDD model by piercing the tail intervertebral disc 5 mm. One week after modeling， rats in the low-dose and high-dose ZGD groups were given 6.24 and 12.24 g/（kg·d） of the decoction via gastric gavage， respectively. The high-dose ZGD + inhibitor group was given 12.24 g/（kg·d） of the decoction and an intraperitoneal injection of YAP/TAZ inhibitor Verteporfin 10 mg/kg. The sham surgery and model groups were given 5 ml/（kg·d） of normal saline via gavage. The gavage was given once a day， and the intraperitoneal injection was given every other day. After 4 weeks of continuous intervention， the pathological changes of the tail intervertebral discs were observed using HE staining， Oil Red O-Green staining， and Toluidine Blue staining. Immunohistochemistry was used to detect the expression of aggrecan and MMP3 in the nucleus pulposus. TUNEL fluorescence staining was performed to detect apoptosis in the nucleus pulposus， and the apoptosis rate was calculated. Western blot was used to detect the Hippo-YAP/TAZ signaling pathway， including YAP， phosphorylated YAP （p-YAP）， phosphorylated MST1/2 （p-MST1/2）， phosphorylated TAZ （p-TAZ） and apoptosis-related proteins， such as Cleaved Caspase 3， P53， Bcl-2 and Bax. ResultsCompared with sham surgery group， the rats in the model group showed significant degenerative changes in the intervertebral disc. The levels of aggrecan， Bcl-2， and YAP proteins in the nucleus pulposus decreased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate increased （P < 0.01）. Compared with the model group， the drug intervention groups showed partial recovery in intervertebral disc degeneration. The levels of aggrecan， Bcl-2， and YAP proteins increased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate decreased （P＜0.05 or P＜0.01）. The high-dose ZGD group showed more significant recovery in intervertebral disc degeneration compared to the low-dose ZGD group， with a decrease in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and an increase in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. Compared with the high-dose ZGD group， the high-dose ZGD + inhibitor group showed a reduced recovery in intervertebral disc degeneration， with an increase in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and a decrease in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. ConclusionZGD may delay intervertebral disc degeneration by inhibiting the phosphorylation of YAP in the nucleus pulposus， maintaining the function of the Hippo-YAP/TAZ signaling pathway， and reducing apoptosis of nucleus pulposus cells.

Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (⁹⁰Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent ⁹⁰Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of ⁹⁰Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (^99mTc-MAA) perfusion test and received the ⁹⁰Y-SIRT; one patient received ⁹⁰Y-SIRT after the second ^99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of ⁹⁰Y-SIRT for treating malignant liver tumors are mild, indicating good safety.

[Objective] To study the inter-allelic recombination event occurring in the HLA-B locus, and to evaluate the molecular genetic mechanisms of a novel HLA allele, predict and analyze the impact of its amino acid residue changes on the three-dimensional structure. [Methods] HLA typing was taken with polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) by Luminex. Sequence-based typing (SBT) and gene clone were used to analyze exons 1-4 sequences of HLA-B allele. In order to determine the exact site of inter-allelic recombination event occurring in the HLA-B locus, sequences of the HLA-B alleles were compared with the IMGT/HLA database by the program “Alignment”. After homology modeling using the Swiss-Model software, the three-dimensional structure of the molecules was simulated using the Swiss Pdb Viewer software, and the FATCAT online software was used to compare the differences in the three-dimensional structures of the molecules. [Results] HLA typing indicated the PCR-SSOP pattern did not match with any known HLA-B alleles, suspected to be a new HLA allele. The genetic clone sequencing results showed HLA-B alleles of the proband were B^*13∶02 and a novel allele. The HLA-B exon2 nucleotide sequence of the novel allele was different from any other known alleles. The novel allele has 12 nucleotides replaced when compared with the closest matching B^*35∶01∶01∶01 allele from c.259 to c.299, which result in 8 amino acids changes. The sequence was identical in B^*35∶01∶01∶01 in exon 1, exon 3, exon 4, intron 1, intron 2, intron 3 and at c.74 to c.258 in exon 2, and c.259 to c.343 sequence in exon 2 was identical in B^*46∶01∶01 by blast search. The structure of the mutant alleles was similar to that of B^*35∶01∶01∶01 and B^*46∶01∶01, and the local hydrogen bonds of amino acids p.63-p.79 were changed at the recombination site. [Conclusion] This study demonstrates a rare inter-allelic recombination event occurring in the HLA-B locus. It has been officially designated as HLA-B^*35∶186 by WHO Nomenclature Committee for Factors of the HLA System. It illustrates the process of novel allele, and provides new evidence for the further studying mechanisms of gene recombination and HLA polymorphism.

Micro/nanoplastics (MNPs), recognized as emerging environmental pollutants, are widely distributed in natural environments. Due to their small particle size and significant migratory capacity, MNPs can infiltrate diverse environmental matrices, then invade and accumulate in the organism via the skin, respiration, and digestion. Recently, concerns have grown over the detrimental effects and potential toxicity of MNPs on reproductive health. This review summarized published epidemiological and toxicological studies related to MNPs exposure and their effects on reproductive health. Firstly, this review critically examined the current landscape of epidemiological evidence and found that MNPs (e.g., polystyrene, polypropylene, polyvinyl chloride, polyethylene, etc.) are present in various biological specimens from both males and females, and their presence may be associated with an increased risk of reproductive disorders. Secondly, extensive toxicological studies revealed that MNPs exposure induces reproductive health damage through mechanisms such as disrupting the microstructure of reproductive organs and altering molecular-level expressions. Oxidative stress, inflammatory responses, and apoptosis are identified as potential links between MNPs exposure and reproductive damage. Finally, this review addressed the prevalent shortcomings in existing studies and proposed future directions to tackle the challenges posed by MNPs-induced reproductive harm. These insights aim to inform strategies for safeguarding public reproductive health and ecological security, providing a scientific foundation for mitigating risks associated with MNPs pollution.

BACKGROUND:Platelet-derived extracellular vesicles are the most abundant vesicles in the circulation,rich in bioactive molecules,genetic material,proteins and other information molecules,involved in cellular communication and material exchange,not only has good procoagulant activity,but also has the promotion of tissue repair and regeneration,and has a wide range of applications in regenerative medicine. OBJECTIVE:To elaborate the secretion mechanism of platelet-derived extracellular vesicles,their application in regenerative medicine,and limiting factors for clinical transformation,and to provide some theoretical support for the clinical translation of platelet-derived extracellular vesicles. METHODS:A computerized search of the PubMed database from January 2005 to August 2023 was applied to articles relating to platelet-derived extracellular vesicles with the search terms"platelet-derived,platelet-rich plasma,extracellular vesicles,isolated,microvesicles exosomes,applications".A total of 62 articles that met the subject criteria were finally included. RESULTS AND CONCLUSION:(1)Activated platelet-derived extracellular vesicles produce two types of vesicles,platelet-derived microparticles,whose secretion may be associated with the asymmetry of the actin cytoskeleton,and platelet-derived exosomes,which may be associated with the regulation of H+-ATPase.(2)Platelet-derived extracellular vesicles are potential effectors of platelet concentrates and platelets themselves,and may intervene in tissue regeneration by promoting angiogenesis,influencing cellular behavior,promoting coagulation and hemostasis,and exerting inflammatory effects.(3)Platelet-derived extracellular vesicles have been reported preclinically in the field of regenerative medicine such as tissue injury,muscle regeneration,cartilage regeneration,and osteoarthritis,and clinical trial data are available as potential therapeutic approaches for wound healing.However,factors such as isolation methods,sample sources,and the types of activators limit the clinical translation of platelet-derived extracellular vesicles into the field of regenerative medicine.(4)In the future,platelet-derived extracellular vesicles may become a cell-free alternative to platelet-rich plasma in regenerative medicine,but the clinical translation of platelet-derived extracellular vesicles needs to actively search for specific markers to differentiate platelet-derived microparticles from platelet-derived exosomes.The mechanism of activator-stimulated platelet-derived extracellular vesicle production,as well as the optimal method of platelet-derived extracellular vesicle collection,the optimal method of storage,the shelf life of the platelet-derived extracellular vesicles,the recommended dosage of platelet-derived extracellular vesicles for clinical application,and the optimal clinical indications need to be further investigated.

BACKGROUND:Transcranial magneto-acoustic-electrical stimulation is a novel non-invasive neural regulation technique that utilizes the induced electric field generated by the coupling effect of ultrasound and static magnetic field to regulate the discharge activity of the nervous system.However,the mechanism by which it affects synaptic plasticity in the brain is still not enough. OBJECTIVE:To explore the effect of transcranial magneto-acoustic-electrical stimulation intensity on synaptic plasticity of the prefrontal cortex neural network in mice. METHODS:(1)Animal experiment:Twenty-four C57 mice were equally and randomly divided into four groups:the control group receiving pseudo-stimulation,the 6.35 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,6.35 W/cm2,the 17.36 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,17.36 W/cm2,and the 56.25 W/cm2 stimulation group receiving coupled stimulation of 0.3 T,56.25 W/cm2.The local field potential signals and behavioral correctness were recorded during the execution of T-maze in mice.(2)Modeling and simulation experiments:A neural network model of the prefrontal cortex in mice stimulated by transcranial magneto-acoustic-electrical stimulation was constructed to compare the structural connectivity characteristics of the neural network under different stimulation intensities. RESULTS AND CONCLUSION:Transcranial magneto-acoustic-electrical stimulation could effectively shorten the behavior learning time,improve the working memory ability of mice(P＜0.05),and continue to stimulate the frontal lobe of mice after learning behavior.There was no significant difference in the accuracy of the T-maze behavioral experiment among the experimental groups(P＞0.1).Analysis of local field potential signals in the frontal lobe of mice revealed that transcranial magneto-acoustic-electrical stimulation promoted energy enhancement of β and γ rhythms.As the stimulation intensity increased,there was an asynchronous decrease in β and γ rhythms.Through β-γ phase amplitude coupling,it was found that stimuli could enhance the neural network's ability to adapt to new information and task requirements.Modeling and simulation experiments found that stimulation could enhance the discharge level of the neural network,increase the long-term synaptic weight level,and decrease the short-term synaptic weight level only when the stimulation intensity was high.To conclude,there is a complex nonlinear relationship between different stimulus intensities and the functional structure of neural networks.This neural regulation technique may provide new possibilities for the treatment of related neurological diseases such as synaptic dysfunction and neural network abnormalities.

Objective: To investigate the precise detection methods for weak partial D type 15 and evaluate their implications for blood transfusion safety, along with the development of corresponding strategies. Methods: A combination of serological methods, including the microplate method, indirect antiglobulin tube method, and microcolumn gel card method, was employed to identify RhD-negative and RhD variant samples. RhD-negative samples were screened for the presence of RHD genes using whole-blood direct PCR amplification. Subsequently, RhD variant samples and RhD-negative samples containing RHD genes underwent full-coding-region sequencing of the RHD gene to confirm their genotypes. The genotyping results were further correlated with the serological test findings for comprehensive analysis. Results: Among 615 549 first-time healthy blood donors, 3 401 samples with an RhD-negative phenotype and 156 samples with RhD variant were identified. Of the 3 401 RhD-negative samples, 1 054 were found to harbor RHD genes. Gene sequencing analysis of the 156 RhD variants and the 1 054 serological negative samples revealed that 89 samples contained the RHD 15 (c. 845G>A) allele. Conclusion: The integration of serological testing methods and genotyping technologies for the precise determination of RhD blood type plays a critical role in ensuring the safety and compatibility of blood transfusions.