ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

Objective To evaluate the accuracy of multiparametric imaging on the dual-source CT through acceptance and commissioning testing, and to provide a reference for standardized clinical application. Methods Both the adult and pediatric dual-source CT scanning modes were used to scan the electron density phantom, and identical multiparametric image reconstruction tasks were performed, including the conventional CT images, the mixed CT images, the virtual monoenergetic images, the iodine images, the electron density images, and the effective atomic number images. Results In the adult scanning mode, the virtual monoenergetic CT numbers showed the greatest difference for the cortical bone (1722 HU at 40 keV vs. 30 HU at 80 keV), with smaller differences observed for other materials as their atomic numbers decreased. The pediatric scanning mode exhibited a similar trend, with the largest difference occurring at 40 keV (1393 HU). In the adult scanning mode, the deviations between the theoretical and measured iodine concentration values were all within 5%, whereas in the pediatric scanning mode, the largest deviation was 15% for an iodine concentration of 2.0 mg/mL. For the electron density, the largest deviation between the theoretical and measured values occurred in the LN450 lung (9.18% in the adult scanning mode and 8.96% in the pediatric scanning mode); the deviations for the LN300 lung were all below 7.2%, for aluminum below 6.3%, and for other tissues within 3%. For the effective atomic number, the deviations between the theoretical and measured values were all within 5% in both scanning modes. Conclusion To ensure the accuracy and reproducibility of the dual-source CT applications, a comprehensive acceptance testing protocol should be established to guarantee the safety and precision of the CT localization process.

Objective:To explore the white matter structural characteristics in patients with bipolar disorder(BD)using diffusion tensor imaging(DTI)and investigate their relationship with cognitive function.Methods:A total of 15 patients with BD type Ⅰ and 26 patients with BD type Ⅱ who met the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)diagnostic criteria and 37 normal controls were included.Cognitive function was assessed with the Trail Making Test(TMT)and Repeatable Battery for the Assessment of Neuropsy-chological Status(RBANS).The tract-based spatial statistics(TBSS)method was used to explore the differences in fractional anisotropy(FA)and mean diffusivity(MD)among the three groups and perform correlation analyses with cognitive function.Results:Patients with BD Ⅰ and BD Ⅱ had lower scores in attention(P＜0.001),delayed memory(P＜0.01),and total scores(P＜0.001)on the RBANS compared to the normal control group.They also exhibited lower FA values in the corpus callosum and right superior corona radiata compared to the normal control group(P＜0.05).In the BD Ⅰ group,there was a positive correlation between FA values in the genu of corpus cal-losum and visuospatial/constructional scores(r=0.74,P＜0.05),while in the BD Ⅱ group,a positive correlation was found between FA values in the same region and language function scores(r=0.55,P＜0.05).Conclusion:It suggests that patients with bipolar disorder may have impaired white matter integrity in the corpus callosum and right superior corona radiata,which may be associated with cognitive impairment.

Objective:To learn about the single nucleotide polymorphism (SNP) population structure and regional distribution characteristics of Yersinia pestis in the natural focus of plague in Qinghai-Tibet Plateau. Methods:A total of 319 representative strains of Yersinia pestis isolated from natural focus of plague in Qinghai-Tibet Plateau from 1954 to 2020 were selected, and 2 298 SNP loci included in the global Yersinia pestis phylogenetic tree were compared by whole genome sequencing technology. MEGA 6.0 software was used to construct phylogenetic trees of 319 strains of Yersinia pestis from Qinghai-Tibet Plateau, determine the SNP population structure of Yersinia pestis in the focus, and describe its regional distribution characteristics. Results:The 319 strains of Yersinia pestis isolated from Qinghai-Tibet Plateau natural plague foci were distributed in 5 clades, namely 1.IN, 2.ANT, 3.ANT, 0.PE and 2.MED. The 1.IN clade contained 209 strains (65.52%, 209/319), which was the dominant population of strains in Qinghai Province, accounting for 90.51% (143/158). The 2.ANT clade contained 83 strains (26.02%, 83/319), which was the dominant population in Tibet Autonomous Region, accounting for 67.24% (78/116). The 3.ANT, 0.PE, and 2.MED clades contained 12 (3.76%, 12/319), 9 (2.82%, 9/319) and 6 strains (1.88%, 6/319), respectively, which were scattered in Qinghai Province, Gansu Province, Sichuan Province, Tibet Autonomous Region, and Xinjiang Uygur Autonomous Region under the jurisdiction of Qinghai-Tibet Plateau. Conclusion:The SNP population structure of Yersinia pestis in natural focus of plague in Qinghai-Tibet Plateau is relatively rich, and the strains are distributed in 5 clades: 1.IN, 2.ANT, 3.ANT, 0.PE and 2.MED, showing the distribution characteristics of specific regions.

Sepsis,a syndrome characterized by organ dysfunction caused by infection,exhibits high incidence and mortality.The pathogenesis of sepsis is complex and involves a cascade of immune reactions,with no specific drugs currently available.Sepsis is mainly treated with Western medical supportive therapies such as antibiotics,hemodynamic management,and mechanical ventilation.However,the occurrence of immune cas-cades significantly increases patients'vulnerability to secondary infections,leading to septic shock and unfavor-able prognoses.International consensus indicates that initiating dynamic monitoring of patients'immune function within 48 h post-sepsis diagnosis can effectively decelerate sepsis progression.Extensive studies have indicated that macrophages,serving as the first line of defense in the innate immune system against pathogens,play a vital role in treating immune system disorders by regulating macrophage polarization and the ratio of cytokines activated.Mitophagy,a hot topic in recent years,has increasingly been shown to play a crucial role in regulating inflammatory signal transduction.Promoting mitophagy during the stage of cytokine storm can mitigate uncontrolled infection and excessive inflammation in sepsis,and inhibiting mitophagy during immunosuppression can enhance host immunity,facilitate bacterial clearance,and improve the survival rate of patients.The idea of treating dis-ease before its onset in traditional Chinese medicine(TCM)coincides with the current consensus among sepsis experts on prevention and interception.The TCM therapies such as extracts of Chinese medicine decoction pieces,TCM compound prescriptions,and acupuncture and moxibustion have the effects of clearing heat and detoxifying,activating blood and resolving stasis,reinforcing healthy qi and consolidating root,and purging.These approa-ches dynamically regulate the levels of mitophagy-related proteins,such as phosphatase and tension homology-induced putative kinase 1,Parkin-E3 ubiquitin protein ligase,light chain 3,and p62,while maintaining a suitable ratio between M1 and M2 macrophages.Consequently,they effectively prevent,halt,or even reverse the progression of sepsis,offering a novel perspective on sepsis management by emphasizing prevention before disease onset and controlling development of existing disease.

Objective:To study the clustered regularly interspaced short palindromic repeats (CRISPR) genotype of Yersinia pestis and its regional distribution characteristics in natural plague focus of Tibet Autonomous Region. Methods:A total of 125 representative Yersinia pestis strains isolated from natural plague focus in Tibet Autonomous Region at different times, regions, hosts and vectors were selected as experimental strains, and the phenol chloroform mixed extraction method was used to extract Yersinia pestis DNA. Three pairs of CRISPR primers (for YPa, YPb, YPc locus) were used to amplify the DNA of the experimental strains, and the CRISPR genotype of Yersinia pestis was determined by sequencing. Results:All 125 strains of Yersinia pestis had three CRISPR locus: YPa, YPb, and YPc. A total of 18 spacer were found, including 8 in YPa loci, 6 in YPb loci, and 4 in YPc loci. Two new types of spacers had been discovered, namely b52 and c14. CRISPR typing revealed 10 genotypes, including G1, G7, G7-b4''', G7-b52, G7-c2 -, G8, G22, G22-a4 -, G22-b4''', and G22-c14, of which 6 were newly discovered genotypes. Among the 125 experimental strains, G7 was the main genotype, accounting for 65.6% (82/125), which was distributed in 6 prefecture level citys and 1 region of Tibet Autonomous Region. Next were G22 and G7-c2 - genetypes, accounting for 14.4% (18/125) and 11.2% (14/125), respectively. G22 gene type was distributed in Nagqu, Changdu, Lhasa citys, and Ngari Prefecture, while G7-c2 - genetype was distributed in Shigatse and Shannan cities. Conclusion:The CRISPR locus of Yersinia pestis in natural plague focus of Tibet Autonomous Region is highly polymorphic, and the Yersinia pestis strains with different genotypes have obvious regional distribution characteristics.

ObjectiveTo investigate the effects of thyme herbal tea （BLX） on the proliferation of human coronavirus OC43 （HCoV-OC43） in vitro and in vivo. MethodThe chemical composition of BLX was analyzed by UPLC-MS. The cytotoxicity of BLX in HRT-18 cells and the effect of BLX treatment on the proliferation of HCoV-OC43 in cells were analyzed. Copies of viral gene were detected by real-time PCR. The effect of BLX treatment on the life cycle of HCoV-OC43 was detected by time-of-addition assay. The maximum tolerated dose of BLX and the influences of BLX on the body weight and survival time of suckling mice infected with HCoV-OC43 were determined. The expression of viral protein in the brain and lung tissue was analyzed by immunohistochemistry. ResultThere were 11 chemical components identified in BLX by UPLC-MS. BLX showed the 50% cytotoxic concentration （CC₅₀） of （13 859.56±319） mg·L^-1， the median inhibitory concentration （IC₅₀） of （1 439.09±200） mg·L^-1， and the selection index of 8.26-11.44 for HCoV-OC43 in HRT-18 cells. Compared with the cells infected with HCoV-OC43， BLX at the concentrations of 1 500， 1 000， 500 mg·L^-1 inhibited the proliferation of this virus （P<0.05， P<0.01）. BLX exhibited antiviral effect in the early stage of virus infection， and the inhibition role in the attachment stage was more significant than that in the entry stage （P<0.05）. In the suckling mice infected with HCoV-OC43， BLX at 1200 and 600 mg·kg^-1·d^-1 alleviated the symptoms， prolonged the survival period， reduced the death rate， and down-regulated the mRNA level of nucleocapsid protein in the mice. Moreover， BLX at 1 200 mg·kg^-1·d^-1 down-regulated the expression of nucleocapsid protein in the brain （P<0.01） and the lung （P<0.01）. ConclusionBLX contained multiple antiviral ingredients. It inhibited the proliferation of HCoV-OC43 both in vitro and in vivo by interference with viral attachment. This study provides theoretical reference for the treatment of acute respiratory tract infection with HCoV-OC43 and for further development and application of BLX.

Background Results of genetic testing for antipsychotic drugs can guide the rational use of drugs in clinical practice and help improve the clinical symptoms of patients with schizophrenia.However,there is currently limited evidence in China regarding the impact of genetic testing results on medication adherence,social function and drug side effects of antipsychotic drug treatment.Objective To explore the improvement of clinical symptoms,medication adherence and social function in patients with schizophrenia under the guidance of antipsychotic drug gene testing results and examine the safety of drug treatment,so as to provide references for ifor precise treatment of schizophrenia patients.Methods Patients with acute schizophrenia who received hospitalization at Dazhou Minkang Hospital from July 2019 to August 2021 as well as met the diagnostic criteria of the International Classification of Diseases,tenth edition(ICD-10)were selected as research subjects(n=144).Based on random number table,subjects were divided into study group and control group,with 72 cases in each group.Control group received drug treatment based on the doctor's clinical experience,while study group received drug treatment based on the results of gene testing for antipsychotic drug.Both treatments lasted for 12 weeks.At baseline as well as 2,4,8 and 12 weeks after treatment,Positive and Negative Syndrome Scale(PANSS),8-item Morisky Medication Adherence Scale(MMAS-8),Social Functional Rating Scale(SFRS)and Treatment Emergent Symptom Scale(TESS)were adopted for assessment.Result Time effect and group effect of the reducing rate of PANSS,MMAS-8 and SFRS scores in the groups were statistically significant(Ftime=95.251,6.650,14.101,Fgroup=38.055,58.175,128.221,P<0.01).The interaction effect of the reduction rates of MMAS-8 scores in two groups was statistically significant(Finteraction=5.837,P<0.01).The group effect and interaction effect of the severity scores of drug side effects and patient pain scores in two groups were statistically significant(Fgroup=7.553,81.533,Finteraction=8.693,9.322,P<0.01).Conclusion In terms of improving clinical symptom relief,medication adherence,social function and drug side effects,medication for patients with schizophrenia guided by genetic testing of antipsychotic drugs may be more effective than that relying on medication based on clinical experience.

The innovation of integrating medical treatment and prevention mechanisms is a key task deployed by the government, aiming to promote the construction of a Healthy China and address the prevalent "treatment over prevention" mindset in healthcare services and society. Vaccination is an effective strategy for preventing and controlling infectious diseases; however, adult vaccination rates in China remain low due to insufficient awareness and enthusiasm among the public and healthcare professionals. In recent years, various regions have begun to explore the model of physicians in medical institutions prescribing vaccines to improve vaccination rates. This article analyzes the positioning, current implementation status, and challenges of vaccine prescriptions, and proposes recommendations advocating policy formulation, improving service models and supporting measures, improving funding mechanisms, and strengthening publicity and education to promote the widespread implementation and effectiveness of vaccine prescriptions.