This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

PURPOSE: To judge the injury mode and injury severity of the real human body through the measured values of anthropomorphic test devices (ATD) injury indices, the mapping relationship of lumbar injury between ATD and human body model (HBM) was explored. METHODS: Through the ATD model and HBM simulation, the mapping relationship of lumbar injury between the 2 subjects was explored. The sled environment consisted of a semi-rigid seat with an adjustable seatback angle and a 3-point seat belt system with a seatback-mounted D-ring. Three seatback recline states of 25°, 45°, and 65° were designed, and the seat pan angle was maintained at 15°. A 23 g, 47 km/h pulse was used. The validity of the finite element model of the sled was verified by the comparison of ATD simulation and test results. ATD model was the test device for human occupant restraint for autonomous vehicles (THOR-AV) dummy model and HBM was the total human model for safety (THUMS) v6.1. The posture of the 2 models was adjusted to adapt to the 3 seat states. The lumbar response of THOR-AV and the mechanical and biomechanical data on L1 - L5 vertebrae of THUMS were output, and the response relationship between THOR-AV and THUMS was descriptive statistically analyzed. RESULTS: Both THOR-AV and THUMS were submarined in the 65° seatback angle case. With the change of seatback angle, the lumbar spine axial compression force (F_z) of THOR-AV and THUMS changed in the similar trend. The maximum F_z ratio of THOR-AV to THUMS at 25° and 45° seatback angle cases were 1.6 and 1.7. The flexion moment (M_y) and the time when the maximum M_y occurred in the 2 subjects were very different. In particular, the form of moment experienced by the L1 - L5 vertebrae of THUMS also changed. The changing trend of M_y measured by THOR-AV over time can reflect the changing trend of maximum stress of L1 and L2 of THUMS. CONCLUSION The F_z of ATD and HBM presents a certain proportional relationship, and there is a mapping relationship between the 2 subjects on F_z. The mapping function can be further clarified by applying more pulses and adopting more seatback angles. It is difficult to map M_y directly because they are very different in ATD and HBM. The M_y of ATD and stress of HBM lumbar showed a similar change trend over time, and there may be a hidden mapping relationship.
Humans ; Lumbar Vertebrae/injuries* ; Finite Element Analysis ; Biomechanical Phenomena ; Manikins ; Spinal Injuries/physiopathology*

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*

BACKGROUND: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular disease in previous studies. However, it is unclear whether elderly people with long-term high AIP levels are more likely to develop coronary heart disease (CHD). Therefore, the aim of this study was to investigate the relationship between AIP trajectory and CHD incidence in elderly people. METHODS: 19,194 participants aged ≥ 60 years who had three AIP measurements between 2018 and 2020 were included in this study. AIP was defined as log₁₀ (triglyceride/high-density lipoprotein cholesterol). The group-based trajectory model was used to identify different trajectory patterns of AIP from 2018 to 2020. Cox proportional hazards models were used to estimate the hazard ratio (HR) with 95% CI of CHD events between different trajectory groups from 2020 to 2023. RESULTS: Three different trajectory patterns were identified through group-based trajectory model: the low-level group (n = 7410, mean AIP: -0.25 to -0.17), the medium-level group (n = 9981, mean AIP: 0.02-0.08), and the high-level group (n = 1803, mean AIP: 0.38-0.42). During a mean follow-up of 2.65 years, a total of 1391 participants developed CHD. After adjusting for potential confounders, compared with the participants in the low-level group, the HR with 95% CI of the medium-level group and the high-level group were estimated to be 1.24 (1.10-1.40) and 1.43 (1.19-1.73), respectively. These findings remained consistent in subgroup analyses and sensitivity analyses. CONCLUSIONS There was a significant correlation between persistent high AIP level and increased CHD risk in the elderly. This suggests that monitoring the long-term changes in AIP is helpful to identify individuals at high CHD risk in elderly people.

Objective To explore the improve mechanism of ultra-filtration extract from Angelica Sinensis Radix and Hedysari Radix on kidney injury in diabetic kidney disease(DKD)rats.Methods The diabetes model was prepared by intraperitoneal injection of streptozotocin,and then fed with high sugar and high fat diet.The rats with successful DKD were randomly divided into model group,positive control group and experimental-L,-M,-H groups with 8 cases per group.Additionally,selected 8 Wistar rats as the blank group.The experimental-L,-M,-H groups were given 1.5,3.0 and 6.0 g·kg-1 ultra-filtration extract from Angelica Sinensis Radix and Hedysari Radix by gavage,respectively.The positive control group was given 1.75 × 10-3 g·kg-1irbesartan suspension by gavage.The blank and model groups were given equal volume of pure water by gavage.Six groups were administrated once a day for 12 consecutive weeks.The 24 h-urinary total protein were detected by coomassie brilliant blue method.The protein expression levels of nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1)and andacyl-CoA synthetase long chain family member 4(ACSL4)in kidney tissue were detected by Western blot.Results The 24 h-UTP in the experimental-M,-H groups,positive control group,model group and blank group were(47.70±3.85),(43.57±6.38),(36.80±6.52),(64.34±13.38)and(7.58±3.71)mg;the relative expression levels of Nrf2 protein were 0.86±0.08,0.75±0.06,0.64±0.08,1.09±0.06 and 0.60±0.07;the relative expression levels of HO-1 protein were 0.77±0.04,0.63±0.07,0.47±0.05,1.04±0.06 and 0.34±0.07;the relative expression levels of ACSL4 protein were 0.62±0.07,0.55±0.07,0.46±0.06,1.08±0.07 and 0.30±0.01,respectively.Compared with the model group,the above indexes in the experimental-M,-H groups and positive control group were significantly different(P＜0.05,P＜0.01).Conclusion Ultra-filtration extract from Angelica Sinensis Radix and Hedysari Radix can improve the damage of kidney tissue in DKD rats,and the mechanism may be related to ferroptosis caused by excessive activation of Nrf2/HO-1 signaling pathway.

Objective Postoperative delirium(POD)has become a critical challenge with severe consequences and increased incidences as the global population ages.However,the underlying mechanism is yet unknown.Our study aimed to explore the changes in metabolites in three specific brain regions and saliva of older mice with postoperative delirium behavior and to identify potential non-invasive biomarkers. Methods Eighteen-month-old male C57/BL6 mice were randomly assigned to the anesthesia/surgery or control group.Behavioral tests were conducted 24 h before surgery and 6,9,and 24 h after surgery.Complement C3(C3)and S100 calcium-binding protein B protein(S100beta)levels were measured in the hippocampus,and a metabolomics analysis was performed on saliva,hippocampus,cortex,and amygdala samples. Results In total,43,33,38,and 14 differential metabolites were detected in the saliva,hippocampus,cortex,and amygdala,respectively."Pyruvate""alpha-linolenic acid"and"2-oleoyl-1-palmitoy-sn-glycero-3-phosphocholine"are enriched in one common pathway and may be potential non-invasive biomarkers for POD.Common changes were observed in the three brain regions,with the upregulation of 1-methylhistidine and downregulation of D-glutamine. Conclusion Dysfunctions in energy metabolism,oxidative stress,and neurotransmitter dysregulation are implicated in the development of POD.The identification of changes in the level of salivary metabolite biomarkers could aid in the development of noninvasive diagnostic methods for POD.

Aim To investigate the effects of hedysar-um polybotrys polysacchcaide(HPS)on gastric muco-sal inflammation of diabetic gastroparesis(DGP)rats and its possible mechanism.Methods A total of 62 male Wistar rats were randomly divided into the control group(12)and the modeling group(50).Except for the control group,the remaining rats were given multi-ple intraperitoneal injections of streptozotocin(25 mg ·kg-1 for three consecutive days)and irregular feed-ing of high-sugar and high-fat diet to replicate DGP model.The model rats were randomly divided into the model group(intragastatically purified water),low,medium and high dose HPS groups(50,100,200 mg ·kg-1·d-1)and the metformin group(90 mg· kg-1·d-1),respectively,and the control group was intragastrically treated with equal volume of purified water once a day for eight weeks.The pathological morphology of gastric mucosa was observed by HE stai-ning;the contents of TNF-α,IL-6,GAS and MTL in gastric mucosa were detected by ELISA.The expres-sion of JAK2 and STAT3mRNA in gastric mucosa was detected by RT-PCR.The levels of JAK2 and STAT3 proteins and their phosphorylation in gastric mucosa were detected by Western blot.Results Compared with the control group,the gastric mucosa of the model group showed a large number of inflammatory cells in-filtrated by HE staining.The contents of TNF-α and IL-6 significantly increased(P＜0.01),while the contents of GAS and MTL significantly decreased(P＜0.01).The mRNA expressions of JAK2 and STAT3 significantly increased(P＜0.05).p-JAK2and p-STAT3 significantly increased(P＜0.01).Compared with the model group,gastric mucosal inflammation was improved in each administration group.The con-tents of TNF-α and IL-6 decreased significantly,while the contents of GAS and MTL increased significantly.The mRNA expressions of JAK2 and STAT3 were sig-nificantly reduced.The expressions of p-JAK2 and p-STAT3 significantly decreased(P＜0.05).Conclu-sions HPS can improve gastric mucosal inflammation and repair gastric mucosal damage in rats,and its mechanism may be related to the regulation of JAK2/STAT3 signaling pathway.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the acupoint selection rules of obesity complicated with type 2 diabetes mellitus(T2DM)through R language data mining technology.Methods CNKI,Wanfang,VIP,CBM,PubMed,Embase,Cochrane Library,web of science and other major databases were searched by computer.From the establishment of the database to January 2024,the clinical research literature on acupuncture and moxibustion for the treatment of obesity with T2DM was included.Microsoft Excel 2021 was used to establish a database of acupoint prescriptions.R 4.3.2 and Rstudio software were used to analyze the frequency,meridian tropism,specific acupoints,correlation analysis,association rules and cluster analysis of acupoints.Results A total of 81 articles were included,and 117 prescriptions were extracted.It involves 82 acupoints,and the total frequency of acupoint usage is 1 072 times.The top five acupoints with the highest frequency were Zusanli(ST36),Zhongwan(RN12),Weiwanxiashu(EX-B3),Pishu(BL20),Tianshu(ST25).The meridian selection is mainly based on the stomach meridian of foot yangming,ren meridian,foot taiyang bladder meridian and foot taiyin spleen meridian.The five-shu points are the specific points with the highest frequency of use.Correlation analysis showed that there were three groups of strongly related acupoint groups.The core acupoints were obtained by association rule analysis.Cluster analysis and machine voting were performed on acupoints with frequency ≥ 10 by function,and a total of four cluster acupoint groups were obtained.Conclusion Through R language data analysis,the principle of acupoint selection for acupuncture and moxibustion in the treatment of obesity complicated with T2DM is mainly based on abdominal local acupoints,combined with visceral syndrome differentiation and empirical point selection,which provides effective treatment ideas for acupuncture and moxibustion in the treatment of obesity complicated with T2DM.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.