ObjectiveBased on ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， the chemical constituents of Qili Qiangxin capsules was identified， and their distribution in vivo was analyzed. MethodsUPLC-Q-Orbitrap-MS was used to detect the sample solution of Qili Qiangxin capsules， as well as the serum， brain， heart， lung， spleen， liver and kidney tissues of mice after oral administration. Using the Thermo Xcalibur 2.2 software， the compound information database was constructed， and the molecular formulas of compounds corresponding to the quasi-molecular ions were fitted. Based on the information of retention time， accurate relative molecular mass and fragments， the compounds and their distribution in vivo were analyzed by comparing with the data of reference substances and literature. ResultsA total of 233 compounds， including 70 terpenoids， 60 flavonoids， 23 organic acids， 17 alkaloids， 20 steroids， 7 coumarins and 36 others， were identified or predicted from Qili Qiangxin capsules， 73 of which were identified matching with standard substances. Tissue distribution results showed that 71， 17， 38， 33， 32， 58 and 43 migrating components were detected in blood， brain， heart， lung， spleen， liver and kidney， respectively. Thirty-seven components were absorbed into the blood and heart， including quinic acid， benzoylaconitine benzoylmesaconine and so on. Fourteen components were absorbed into the blood and six tissues， including calycosin， methylnissolin， formononetin， alisol B， alisol A and so on. ConclusionThis study comprehensively analyzes the chemical components of Qili Qiangxin capsules and their distribution in vivo. Among them， astragaloside Ⅳ， salvianolic acid B， ginsenoside Rb₁， ginsenoside Rb₃， ginsenoside Rd， ginsenoside Rg₃， calycosin-7-glucoside， and sinapine may be the important components for the treatment of heart failure， which can provide useful reference for its quality control and research on pharmacodynamic material basis.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

OBJECTIVE To investigate the impact of Tongxinluo capsules on the pharmacokinetics of rivaroxaban in rats. METHODS Rats were randomly divided into rivaroxaban alone group （2.70 mg/kg）， low-dose Tongxinluo capsules combined with rivaroxaban group （Tongxinluo capsules 0.28 g/kg+rivaroxaban 2.70 mg/kg）， and high-dose Tongxinluo capsules combined with rivaroxaban group （Tongxinluo capsules 0.84 g/kg+rivaroxaban 2.70 mg/kg）， with five rats in each group. Following seven consecutive days of gavage with normal saline or the corresponding doses of Tongxinluo capsules， the rats were subjected to a final gavage administration of rivaroxaban. Blood samples were collected at 0 h prior to the final administration and at 0.16， 0.33， 0.50， 0.75， 1， 1.5， 2， 4， 8， 12 and 24 h post-final administration. The plasma concentration of rivaroxaban in rats was determined by high-performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters [peak concentration （cmax）， half-life （t1/2）， area under the drug concentration time curve （AUC）， mean residence time （MRT）， clearance （CL）， apparent volume of distribution （Vd） and peak time （tmax）] of each group were calculated using a non-compartmental model of MonolixSuite 2023R1 pharmacokinetic software. RESULTS Compared with rivaroxaban alone group， AUC₀₋ₜ and AUC0-∞ of rivaroxaban in rats were increased significantly in high-dose Tongxinluo capsules+rivaroxaban group （P＜0.05）， while CL was decreased significantly （P＜0.05）； t1/2 and MRT were shortened， tmax was extended， cmax was increased， while Vd was decreased， but there was no statistical significance （P＞0.05）. CONCLUSIONS Rivaroxaban combined with Tongxinluo capsules significantly increases the plasma exposure of rivaroxaban in rats. Potential drug-drug interactions should be considered in clinical practice based on the co-administration conditions.

Epilepsy affects over 50 million people worldwide. Drug-resistant epilepsy (DRE) accounts for up to a third of these cases, and neuro-inflammation is thought to play a role in such cases. Despite being a long-debated issue in the field of DRE, the mechanisms underlying neuroinflammation have yet to be fully elucidated. The pro-inflammatory microenvironment within the brain tissue of people with DRE has been probed using single-cell multimodal transcriptomics. Evidence suggests that inflammatory cells and pro-inflammatory cytokines in the nervous system can lead to extensive biochemical changes, such as connexin hemichannel excitability and disruption of neurotransmitter homeostasis. The presence of inflammation may give rise to neuronal network abnormalities that suppress endogenous antiepileptic systems. We focus on the role of neuroinflammation and brain network anomalies in DRE from multiple perspectives to identify critical points for clinical application. We hope to provide an insightful overview to advance the quest for better DRE treatments.
Humans ; Drug Resistant Epilepsy/metabolism* ; Neuroinflammatory Diseases/immunology* ; Animals ; Brain/pathology* ; Nerve Net/pathology*

Objective:To observe the effectiveness and safety of the application of Wei nasal jet tube(WNJT)in anesthesia induction for patients with extensive facial burns.Methods:A total of 60 patients who underwent multiple systemic scab removal and skin graft-ing surgery in our hospital from July 2021 to July 2023 were enrolled in this study.The patients were 18-60 years of age,with a body mass index of 18-29 kg/m2,ASA II or III,and Mallampati I-III.Using a random number table method,the patients were divided into WNJT ventilation group(W group)and mask ventilation group(M group),with 30 cases in each group.Before anesthesia induction,WNJT was inserted into one side of the nasal cavity for hand controlled normal frequency supraglottic jet ventilation in group W pa-tients,while oxygen ventilation was administered to group M patients through conventional two-hand clasped face masks.After 5 min,tracheal intubation was performed under a visual laryngoscope.The mean amplitude of diaphragm fluctuations,end expiratory carbon dioxide partial pressure(PETCO2),and blood oxygen saturation(SpO2)measured by ultrasound were recorded during spontaneous respi-ration at 5 min of oxygenation and nitrogen removal(T0),as well as at 1 min(T1),2 min(T2),3 min(T3),4 min(T4),and 5 min(T5,im-mediately before intubation)of anesthetic induction.Arterial blood gas(PaO2 and PaCO2)at T0 and T5 were measured.Heart rate(HR)and mean arterial pressure(MAP)were recorded at T0-T5 in both groups of patients.The occurrence of postoperative pharyngeal pain,facial or mandibular angle bleeding,gastrointestinal bloating,and nasal mucosal bleeding were recorded in both groups of pa-tients.Results:At T0,there were no statistically significant differences in mean amplitude of diaphragm fluctuations,HR,MAP,PaO2,PaCO2,PETCO2,and SpO2 between the two groups of patients.At T1-T5,the HR and MAP of patients in the W group were significantly lower than those in the M group(P<0.05).At T5,the PaO2 of patients in the W group was significantly higher than that in the M group,while the PaCO2 and PETCO2 were significantly lower than those in the M group(P<0.05).However,the difference in SpO2 was not sta-tistically significant.The W group had less facial or mandibular angle bleeding and postoperative gastrointestinal bloating than the M group,and the differences were statistically significant(P<0.05).There were no statistically significant differences between the two groups of patients in postoperative pharyngitis and nasal mucosal bleeding(P>0.05).Conclusion:During general anesthesia induction in patients with extensive facial burns,WNJT has the advantages of good ventilation effect,high safety,less complications such as gas-trointestinal bloating and facial or mandibular angle bleeding,and more stable hemodynamics.WNJT has good application prospects in clinical anesthesia.

Objective To analyze the efficacy of self-formulated Bushen Qianyang Decoction combined with alendronate sodium and vitamin D3 in treating osteoporosis(OP)and to observe its effect on bone metabolism and trimethylamine oxide(TMAO)-nuclear factor κB(NF-κB)/activated T nuclear factor c1(NFATc1)pathway.Methods A total of 102 cases of patients with OP of spleen and kidney yang deficiency type who admitted to Taizhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2021 to January 2023 were randomly divided into an observation group and a western medicine group according to the random number table method,51 cases in each group.The western medicine group was treated with alendronate sodium and vitamin D,and the observation group was treated with self-formulated Bushen Qianyang Decoction on the basis of treatment for the western medicine group,and the course of treatment covered for 12 weeks.The changes of traditional Chinese medicine(TCM)syndrome score,Oswestry Disability Index(ODI)score,pain visual analogue scale(VAS)score,bone metabolism indicators,and levels of TMAO-NF-κB/NFATc1 pathway related factors before and after treatment in the two groups were observed.Moreover,the clinical efficacy and medication safety of the two groups were evaluated.Results(1)After 12 weeks of treatment,the total effective rate of the observation group was 96.08%(49/51),and that of the western medicine group was 78.43%(40/51).The intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the western medicine group(P<0.01).(2)After treatment,the two groups presented the decreased scores of TCM symptoms such as cold pain in the lower back,soreness and fatigue,shortness of breath and reluctance to talk,vertigo and dizziness when compared with those before treatment(P<0.05),and the decrease of TCM syndrome scores in the observation group was significantly superior to that in the western medicine group(P<0.01).(3)After treatment,the ODI scores and pain VAS scores of patients in the two groups were decreased when compared with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the western medicine group(P<0.01).(4)After treatment,the serum osteocalcium(BGP)level in the two groups of patients was increased when compared with that before treatment(P<0.05),and the serum total procollagen type 1 intact N(amino)-terminal propeptide(PINP)and β-collagen degradation product(β-CTX)levels were decreased when compared with those before treatment(P<0.05),and the increase of the serum BGP level and the decrease of the serum PINP and β-CTX levels in the observation group were significantly superior to those in the western medicine group(P<0.01).(5)After treatment,the levels of serum TMAO,NF-κB,and NFATc1 in the two groups of patients were all decreased when compared with those before treatment(P<0.05),and the decrease of the above indicators in the observation group was significantly superior to that in the western medicine group(P<0.01).(6)The total incidence of adverse reactions in the observation group was 5.88%(3/51)and that in the western medicine group was 9.80%(5/51),and the intergroup comparison showed that the difference was not statistically significant between the two groups(P>0.05).Conclusion Self-formulated Bushen Qianyang Decoction combined with alendronate sodium and vitamin D3 exerts certain efficacy in treating OP patients with spleen and kidney yang deficiency type,which can effectively alleviate the symptoms such as cold pain in the lower back,alleviate the degree of dysfunction,improve bone metabolism,and inhibit the high-expressed TMAO,NF-κB,and NFATc1 in the serum.Moreover,the combined therapy does not cause serious adverse reactions,with high safety.

Objective To explore the optimization strategy of Qishen Granules in treating coronary heart disease with heart failure(CHD-HF)based on data mining and the pathogenic"toxin"theory,and to predict its active components and mechanisms using network pharmacology.Methods Literature on traditional Chinese medicine(TCM)for treating CHD-HF was collected from relevant databases,and prescriptions were screened and established into a database according to inclusion and exclusion criteria.Frequency,association rules,and hierarchical clustering analyses were performed using the Ancient and Modern Medical Case Cloud Platform.Network pharmacology techniques were applied to screen potential targets of the optimized combination for treating CHD-HF,and carry out the targets and pathways enrichment analysis.Results A total of 336 articles and 339 prescriptions involving 191 herbs were included,with 12 herbs used more than 100 times.The core drug combinations for treating CHD-HF included Astragali Radix,Poria,Salviae Miltiorrhizae Radix et Rhizoma,Glycyrrhizae Radix et Rhizoma,Chuanxiong Rhizoma,etc,while commonly used detoxifying herbs included Leonuri Herb,Coptidis Rhizoma,etc.Association rule analysis yielded 10 two-item associations and 17 three-item associations;clustering analysis grouped the data into 5 categories.Based on data mining and the pathogenic"toxin"theory,the combination for treating CHD-HF was optimized to include Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Aconiti Lateralis Radix Praeparata,Glycyrrhizae Radix et Rhizoma,Coptidis Rhizoma,and Taraxaci Herba.Network pharmacology analysis identified 366 common targets between the optimized combination and CHD-HF,with 16 core targets screened out.Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed significant enrichment in pathways such as cancer pathways,lipid and atherosclerosis,Rap1 signaling pathway,hypoxia-inducible factor 1(HIF-1)signaling pathway,phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt)signaling pathway,Ras signaling pathway,and mitogen-activated protein kinase(MAPK)signaling pathway.Conclusion TCM treatment for CHD-HF primarily focuses on replenishing qi and warming yang,activating blood circulation and resolving fluid retention.Based on data mining results and the pathogenic"toxin"theory,the formulation strategy of Qishen Granules for treating CHD-HF was optimized,potentially exerting therapeutic effects through anti-inflammatory,anti-apoptotic,and anti-hypoxia physiological processes.

Objective To construct a database for molecular mass spectra of toxins and drugs in order to facilitate the management and retrieval of mass spectra for nerve agents,metabolites and other small molecules.Methods Requirement analysis and functional design were performed using software engineering methods.The Spec2Vec algorithm was used for vector representation of mass spectra,while SMILES molecular structures were vectorized using the extended connectivity fingerprint(ECFP).A data storage model integrating structured information and vector representations was established using the Milvus database.Similarity search of mass spectra and molecular structures was conducted via vector similarity comparison and the FlashEntropySearch algorithm.Results The constructed database of mass spectra encompassed over 400,000 entries from such sources as OCAD,NIST,MASSBANK,metabolic products,and natural products of TCM,which was capable of searching for similarities in mass spectra and molecular structures.On a standard server,similarity search of mass spectra took no more than 5 seconds,while that of molecular structures took no more than 1 second.Conclusion The system enables efficient management of complex mass spectra and provides rapid retrieval and comparison of mass spectra-related information through advanced vector indexing technology,offering robust data support and research tools for toxicology and pharmacology.