ObjectiveTo investigate the effect and mechanism of Shuangshen Ningxin capsules （SSNX） in regulating the nuclear factor-κB （NF-κB） and mitogen-activated protein kinase （MAPK） pathways to inhibit inflammation and alleviate myocardial ischemia-reperfusion injury （MIRI） in rats. MethodsThe 45 healthy male Sprague-Dawley （SD） rats were divided into sham operation group， model group， and SSNX capsules group （90 mg·kg^-1）. The left anterior descending coronary artery was ligated to establish the MIRI model. Cardiac function was evaluated by echocardiography， and microvascular reperfusion was analyzed using contrast echocardiography. Myocardial inflammation and injury were assessed by hematoxylin and eosin （HE） staining， immunohistochemistry， and TdT-mediated dUTP nick end labeling （TUNEL）. The expression levels of cardiac inflammatory cytokines， including interleukin-1α （IL-1α）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. Core differentially expressed genes （DEGs） and enriched pathways were screened by transcriptome sequencing. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to verify the mRNA expression of Toll-like receptor 2 （TLR2）， chemokine （C-X-C motif） ligand 1 （CXCL1） and prostaglandin-endoperoxide synthase 2 （PTGS2）， as well as the protein expression of Caspase-3， cleaved Caspase-3， p-NF-κB/NF-κB， phosphorylated extracellular signal-regulated kinase 1/2 （p-ERK1/2/ERK1/2） and p-p38 MAPK/p38 MAPK. ResultsCompared with the sham operation group， the ejection fraction （EF）， fractional shortening （FS）， stroke volume （SV） and cardiac output （CO） of the model group were significantly decreased （P<0.01）， the peak time of myocardial perfusion was prolonged （P<0.01）， hypoxia-inducible factor （HIF）-1α and α-smooth muscle actin （SMA） expression increased （P<0.01）， the concentrations of inflammatory factors IL-1α， IL-6， TNF-α， TLR2， CXCL1 and PTGS2 increased （P<0.01）， and the expression of cleaved Caspase-3， p-NF-κB/NF-κB， p-ERK1/2/ERK1/2 and p-p38 MAPK/p38 MAPK proteins was significantly increased （P<0.01）. SSNX could improve cardiac function （P<0.05， P<0.01）， and significantly shorten the peak time of myocardial perfusion （P<0.01）. Moreover， it could also down-regulate HIF-1α and a-SMA expression （P<0.05， P<0.01）， and reduce the concentrations of IL-1α， IL-6， TNF-α （P<0.01）， and the mRNA expression of TLR2， CXCL1 and PTGS2 （P<0.01）. Additionally， SSNX inhibited the apoptosis rate （P<0.01） and significantly reduced the expression of Cleaved Caspase-3， p-NF-κB/NF-κB， p-ERK1/2/ERK1/2 and p-p38 MAPK/p38 MAPK proteins （P<0.01）. ConclusionSSNX can alleviate cardiac inflammation by regulating the NF-κB and MAPK signaling pathways， thereby effectively preventing and alleviating myocardial reperfusion injury.

A scoping review was performed to systematically search and summarize the clinical research in the treatment of dysmenorrhea with oral Chinese patent medicines. The oral Chinese patent medicines for treating dysmenorrhea in three major drug lists, guidelines, and textbooks were screened, and the relevant clinical trials were retrieved from eight Chinese and English databases. The key information of the included trials was extracted and visually analyzed. A total of 50 Chinese patent medicines were included, among which oral Chinese patent medicines for the dysmenorrhea patients with the syndrome of Qi stagnation and blood stasis accounted for the highest proportion, and the average daily cost varied greatly among Chinese patent medicines. A total of 150 articles were included, involving 22 Chinese patent medicines, among which Guizhi Fuling Capsules/Pills, Sanjie Zhentong Capsules, and Dan'e Fukang Soft Extract were the most frequently studied. These articles mainly reported randomized controlled trial(RCT), which mainly focused on the comparison of the intervention effect between Chinese patent medicines combined with western medicine and western medicine alone, and the sample size was generally 51-100 cases. The high-frequency outcome indicators belonged to nine domains such as effective rate, adverse reactions, and laboratory examinations. This study showed that oral Chinese patent medicines had advantages in the treatment of dysmenorrhea, and the annual number of related clinical trials showed an overall growing trend. However, there were still problems such as insufficient safety information and vague description of traditional Chinese medicine(TCM) syndromes types in the instructions of Chinese patent medicines. The available clinical research had shortcomings such as uneven distribution of Chinese patent medicines, limited research scale, poor methodological rigor, and insufficient standardization of outcome indicators. In the future, it is necessary to deepen the development of high-quality clinical research and improve the contents of the instructions to ensure the effectiveness and safety of the clinical application of oral Chinese patent medicines in the treatment of dysmenorrhea.
Dysmenorrhea/drug therapy* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Administration, Oral ; Nonprescription Drugs/administration & dosage*

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective To evaluate the changes in postoperative plasma β-endorphin(β-EP)levels in patients who had received perioperative electroacupuncture(EA)treatment in 10 randomized controlled trials(RCTs)and examine the impact of EA on postoperative pain.Methods This meta-analysis evaluated the changes in plasma β-EP levels and visual analog scale(VAS)12,24 and 48 hours after surgery in patients receiving perioperative EA.It also assessed the changes in plasma serotonin(5-hydroxytryptamine,5-HT)and prostaglandin E2(PGE2)levels at 24 hours postsurgery.A comprehensive search was conducted in the China National Knowledge Infrastructure(CNKI),Wanfang,Chongqing VIP database,Chinese Biomedical Database(CBM),Web of Science,and PubMed databases.RCTs on perioperative EA and β-EP published from the inception of the websites up to July 25,2023,were retrieved.Effect size aggregation,literature quality assessment,and bias analysis were performed using RevMan 5.3 software,and sensitivity analysis was conducted via R 4.3.1.Results A total of 10 RCTs involving 706 patients were included.EA in conjunction with conventional anesthesia significantly increased plasma β-EP levels at 12 hours postsurgery[standard mean difference(SMD)=2.79,95%CI(1.85,3.72),Z=5.81,P＜0.00001],24hours postsurgery[SMD=1.87,95%CI(0.9,2.83),Z=3.79,P=0.0001],and 48 hours postsurgery[SMD=2.02,95%CI(1.49,2.54),Z=7.50,P＜0.00001].EA reduced plasma PGE2 levels at 24 hours postsurgery and plasma 5-HT levels at 24 hours postsurgery,and the VAS at 12,24 and 48 hours after surgery also decreased.Conclusion These findings suggest that perioperative EA markedly elevates plasma β-EP levels,reduces pain-inducing factors in plasma,and effectively alleviates acute postoperative pain.

Objective To compare the capture performance differences between TruSeq? Exome and NimbleGen SeqCap EZ Human Exome kits in children with cerebral palsy(CP),and to provide a technical selection basis for clinical genetic research and diagnosis.Methods Peripheral blood samples from 48 sporadic CP patients were included.Exome libraries were constructed using TruSeq(DNA probes)and NimbleGen(RNA probes),followed by sequencing on the Illumina HiSeq 2000 platform.Bioinformatics analysis was applied to evaluate mapping rate,target region coverage,variant concordance,and clinical relevance based on a CP-related gene set(2 293 genes).The statistical analysis was performed using a paired t-test with a significance threshold of α=0.05.Results The results showed no significant differences between NimbleGen and TruSeq exome capture kits in basic data quality(alignment rate,insert size)and GC content.However,they exhibited complementary characteristics in key performance metrics:NimbleGen demonstrated superior performance in specific depth coverage(1×coverage rate,P=1.84×10-5;20×coverage rate,P=1.49×10-20).TruSeq,on the other hand,showed higher sensitivity in Indel detection(TruSeq vs.NimbleGen:11 371±1 689 vs.11 274±1 670,P=3.24×10-7)and rare variant capture(TruSeq vs.NimbleGen:3 164±766 vs.3 072±774,P=1.20×10-4),successfully identifying all 11 pathogenic variants(including 2 missed by NimbleGen).Conclusion TruSeq,with its superior variant detection rate,is more suitable for clinical diagnostic applications,while NimbleGen's coverage stability may be advantageous for research-oriented projects.

Objective To compare the capture performance differences between TruSeq? Exome and NimbleGen SeqCap EZ Human Exome kits in children with cerebral palsy(CP),and to provide a technical selection basis for clinical genetic research and diagnosis.Methods Peripheral blood samples from 48 sporadic CP patients were included.Exome libraries were constructed using TruSeq(DNA probes)and NimbleGen(RNA probes),followed by sequencing on the Illumina HiSeq 2000 platform.Bioinformatics analysis was applied to evaluate mapping rate,target region coverage,variant concordance,and clinical relevance based on a CP-related gene set(2 293 genes).The statistical analysis was performed using a paired t-test with a significance threshold of α=0.05.Results The results showed no significant differences between NimbleGen and TruSeq exome capture kits in basic data quality(alignment rate,insert size)and GC content.However,they exhibited complementary characteristics in key performance metrics:NimbleGen demonstrated superior performance in specific depth coverage(1×coverage rate,P=1.84×10-5;20×coverage rate,P=1.49×10-20).TruSeq,on the other hand,showed higher sensitivity in Indel detection(TruSeq vs.NimbleGen:11 371±1 689 vs.11 274±1 670,P=3.24×10-7)and rare variant capture(TruSeq vs.NimbleGen:3 164±766 vs.3 072±774,P=1.20×10-4),successfully identifying all 11 pathogenic variants(including 2 missed by NimbleGen).Conclusion TruSeq,with its superior variant detection rate,is more suitable for clinical diagnostic applications,while NimbleGen's coverage stability may be advantageous for research-oriented projects.

The correlations of global/local properties of brain networks with gambling behavioral scales in depression are explored.The task-state brain functional magnetic resonance imaging data of 24 patients with gambling behavior and depression and 24 healthy controls are analyzed,and preprocessed by SPM software.Graph theory analysis method is used to establish the functional brain networks in which local and global properties are calculated.Two sets of local attribute index including node degree and node efficiency are used to make edge analysis in different depression groups(major,moderate and mild depression groups,with 8 patients in each group)and healthy control group,and the changes in global properties are also discussed.Additionally,the correlations of scoring scale related to gambling behavior with 3 criteria on the global properties(small world attribute,global efficiency and local efficiency)are analyzed.The two-sample t-tests on depression groups and healthy control group confirm the significant connections among brain regions(P＜0.05),and reveal the significant negative correlations between the global brain network attribute indexes and different behavioral scales,which fully verifies the correlation between gambling behavior and depression,and provides the basis for further exploring correlation between the individual behavior attribute and depression,thereby assisting clinical diagnosis and treatment of depression patients.

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×10⁹, 0.50×10⁹, 0.48×10⁹, 0.48×10⁹/L to 1.48×10⁹, 3.04×10⁹, 1.10×10⁹, 0.73×10⁹/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.
Humans ; Child ; Child, Preschool ; Adolescent ; Prospective Studies ; Glycogen Storage Disease Type I/drug therapy* ; Neutropenia ; Abdominal Pain ; Diarrhea/drug therapy* ; Hypoglycemia

OBJECTIVE: To analyze the feasibility of using vascular plaque quantification (VPQ) to evaluate carotid atherosclerotic plaques and to observe the effect of statins on carotid atherosclerotic plaques. METHODS: Patients with carotid plaques from January 2016 to September 2018 in Peking University First Hospital Neurology Department were recruited and underwent three-dimonsional ultrasound (3DUS). Their gray scale median (GSM) and other parameters of carotid plaques were measured with VPQ. The patients were divided into low GSM group (GSM < 40) and high GSM group (GSM≥40). The clinical characteristics and plaque characteristics of the patients in the two groups were compared to analyze the stability of plaques. According to whether taking statins or not, the patients were further divided into statin group and non-statin group, plaque GSM and other parameters of their carotid plaques were measured and the changes of carotid plaques at the end of 3 months and 2 years were observed. RESULTS: A total of 120 patients were enrolled, including 79 males and 41 females, with an average age of (65.39±9.11) years. The patients were divided into low GSM group (31 cases) (GSM < 40) and high GSM group (89 cases) (GSM≥40). The stenosis of the lumen in the low GSM group was more severe (the area stenosis rate was 41.32%±21.37% vs. 29.79%±17.16%, P < 0.05). The nor-malized wall index (NWI) of plaque in low GSM group was significantly higher than that in high GSM group (0.61 ±0.14 vs. 0.52±0.12, P < 0.01). A total of 77 patients, including 51 males and 26 females, aged (64.96±9.58) years, were enrolled to observe the statin effects on carotid plaque. They were divided into statin group (n=56) and non-statin group (n=21) according to whether taking statins or not. At the baseline and 3-month follow-up, there were no significant differences in carotid plaque volume, area, degree of luminal stenosis and GSM between the two groups (P>0.05). At the end of the 2-year follow-up, GSM increased in the statin group [median 10.00 (2.00, 28.00)] but decreased in the non-statin group [median －7.00 (－11.00, 5.50)], with a statistically significant difference between the two groups (P < 0.01). There was no significant increase in carotid plaque volume in the statin group, while there was a slight increase in the non-statin group, but there was no significant difference between the two groups [median increase in plaque volume was 0.00 (－30.00, 40.00) mm³ in the statin group and 30.00 (10.00, 70.00) mm³ in the non-statin group, P>0.05]. CONCLUSION The VPQ technology of 3DUS can be used to evaluate carotid atherosclerotic plaques. Patients with low GSM (GSM < 40) have more severe vascular stenosis and higher normalized wall index. VPQ technology can also be used to observe the effect of statins on carotid plaque, the GSM of plaques increase in patients who are taking moderate-intensity statin treatment for two years.
Aged ; Carotid Stenosis/diagnostic imaging* ; Constriction, Pathologic ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Male ; Middle Aged ; Plaque, Atherosclerotic/drug therapy* ; Technology ; Ultrasonography

ObjectiveTo explore the material basis and mechanism of Nardostachyos Radix et Rhizoma （NRER）-Agrimoniae Herba （AH）， the herbal pair effective in regulating the liver， invigorating Qi， and calming palpitations， in the treatment of premature ventricular contractions （PVCs） by network pharmacology and molecular docking. MethodThe chemical components and targets of NRER and AH were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） combined with relevant literature. GeneCards，Online Mendelian Inheritance in Man（OMIM），and DrugBank were used to predict the potential targets against PVCs. STRING platform was used for protein-protein interaction （PPI） analysis. Metascape platform was used for Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis. Cytoscape 3.8.0 was used to construct the NRER-AH component-potential target-signaling pathway network. The main target proteins underwent molecular docking to the active components of NRER-AH by AutoDock 4.2.6. ResultThe targets of nine active components in NRER-AH （such as quercetin，kaempferol，and acacetin） against PVCs mainly involved tumor necrosis factor （TNF），mitogen-activated protein kinase 1（MAPK1），and protein kinase B1（Akt1）. The potential targets were mainly enriched in 26 signaling pathways，such as pathways in cancer and the advanced glycosylation end product （AGE）-receptor of advanced glycosylation end product（RAGE） signaling pathway. The results of molecular docking showed that the majority of the active components （92.59%） of NRER-AH had good binding activities with the main target proteins TNF，MAPK1，and Akt1. ConclusionThe active components of NRER-AH can regulate cardiac ion channels，resist inflammation， and combat oxidative stress to treat PVCs through multi-target and multi-pathway interventions. They can also improve symptoms related to depression and anxiety by inhibiting monoamine oxidase activity and protecting nerves from damage. This study is expected to provide research ideas and the theoretical basis for further exploring the material basis and mechanism of NRER-AH in the treatment of PVCs.