This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals ; Mice ; Milk/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Male ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/drug effects* ; Interleukin-1beta/immunology* ; Tandem Mass Spectrometry ; Female

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

Objective To explore the differences in stress distribution and stability of the planta pedis in the patients with unilateral and bilateral plantar fasciitis(PF)through plantar stress and center of pressure(COP)analysis.Methods A total of 100 patients with PF visiting in this hospital were enrolled,among them 50 cases were unilateral heel pain(unilateral heel pain group)and 50 cases were bilateral heel pain(bilateral heel pain).Meanwhile,50 healthy subjects were included(healthy group).In the health group and bilateral heel pain groups,the average stress value of both planta pedis surfaces of each subject was taken and named as the J0 group and H2 group,respectively.In the unilateral heel pain group,the plantar stress in 50 healthy feet and 50 affected feet were named as the J1 group and H1 group,respectively.The plantar pedis was divided into 10 regions for analysis and comparison[the first foot toe(T1),T2-5,the first-fifth metatarsal bones(M1-M5),the mid foot(MF),heel medial side(MH),heel lateral side(LH)].The subjects in 3 groups conducted the static and dynamic tests respectively,and the differences in plantar stress distribution and COP parameters among the J1,H1,H2 and J0 groups were compared respectively.Results In the static tests,the maximum pressure of the LH regions in the group J1 was increased when compared with the group J0,the contact area of LH regions in the group H1 was reduced when compared with the group J0,the maximum pressure of the M2 and M3 regions in the H1 group was increased when compared with the group J0,the contact areas of the MH and LH regions in the H2 group were decreased when compared with the group J0,the maximum pressure of the M1 region was increased when compared with the group J0,and the differences were statistically significant(P<0.05).In the dynamic tests,the maximum pressure of the T2-5 regions in the J1 group was increased when compared with the J0 group,the maximum pressure of the M3 region in the group H1 was increased when compared with the group J0,the maximum pressure of the M3 and M4 region in the group H2 was in-creased when compared with the group J0,and the differences were statistically significant(P<0.05).The COP 95%confidence ellipse area in the health group was the smallest,followed by the bilateral heel pain group,and finally the unilateral heel pain group,and the differences among 3 groups were statistically signifi-cant(P<0.05),there was also statistically significant difference between pairwise comparisons in 3 groups(P<0.05).Conclusion In the static condition,the pressure of the healthy heel and affected forefoot in the patients with PF is increased;while in the dynamic condition,the pressure of the toes of the healthy foot and forefoot of the affected foot in the patients with PF is also increased.The distribution of plantar stress in the patients with PF has larger difference compared with the healthy population,and the stability is poor.Meas-ures can be taken to improve the abnormal force on the foot,reduce pain and reduce the risk of falling.

Objective To investigate the biomechanical differences in plantar pressure,postural stability,and plantar Visual Analogue Scale(VAS)scores between normal feet and unilateral/bilat-eral pes cavus,reveal their unique neuromechanical compensation mechanisms,and construct a sta-bility early warning model based on the minimum center of pressure(COP)trajectory classification.Methods A total of 70 patients with pes cavus from December 2023 to October 2024 were selected as study subjects,including 33 patients in the unilateral pes cavus group and 37 patients in the bilat-eral pes cavus group.During the same period,32 normal feet were included as normal foot group.A flat-panel plantar pressure testing system was used to collect dynamic plantar pressure data and COP trajectories from three groups at a self-selected walking speed.There were no statistically significant differences in baseline data such as age,gender,and body mass index among the three groups(P＞0.05).One-way analysis of variance and the Wilcoxon rank-sum test were used to compare the differences in maximum pressure,contact area,VAS scores,and the 95％confidence ellipse area of the COP among the three groups in 10 plantar regions.Results Patients with pes cavus exhibited lower peak pressure in the MF region compared to normal feet,while higher peak pressure in the M2,M3,and MH regions.Patients with bilateral pes cavus showed lower peak pressure in the T1 region compared to normal feet,and patients with unilateral pes cavus had lower peak pressure in the LH region compared to the normal group(P＜0.05).The plantar contact area in patients with pes cavus was reduced in the T1,M2,M3,M4,MF,and MH regions compared to normal feet(P＜0.05).The 95％confidence ellipse area of the COP was larger in both the bilateral and uni-lateral pes cavus groups compared to the normal foot group(P＜0.001).Unilateral pes cavus pres-ented a specific lateral COP drift(amplitude of 3 to 4 cm),which is a biomechanical manifestation of compensatory eversion of the unaffected foot.Patients with bilateral pes cavus exhibited a"bimod-al oscillation"trajectory(amplitude of 6 to 8 cm),suggesting possible vestibular-spinal regulatory dysfunction and the poorest postural stability.In the pes cavus group,there was a significant in-crease in pressure in the M2,M3,and MH regions,with peak pressures exceeding 190 kPa in pa-tients with bilateral pes cavus,which was highly correlated with plantar pain and could serve as a pain early warning threshold.Conclusion Unilateral and bilateral pes cavus exhibit significantly different neuromechanical compensation patterns.The classification based on the"lateral drift"and"bimodal oscillation"characteristics of the COP trajectory can serve as a stability early warning indi-cator for assessing fall risk.Decompression interventions targeting the key pressure regions of M2,M3,and MH(such as customized orthotic insoles)are the core strategies for alleviating pain and optimizing dynamic gait stability.

Objective To formulate a pharmaceutical service pathway to standardize the pharmacists'whole process of pharmaceutical services for breast cancer patients in medical institutions,promote the standardization of pharmacists'work and improve the rationality of drug use for breast cancer patients in medical institutions.Methods The editorial committee aimed at several challenging problems in the whole process of pharmaceutical services for breast cancer patients in medical institutions through systematic search,referring to the latest domestic and international guidelines and expert consensus of breast cancer and under the relevant drug administration regulations in China,collected and sorted out the professional opinions of doctors,pharmacists,and methodological experts,developed questionnaires and held two rounds of expert argumentation meetings,and finally screened out the most valuable results.The whole process management pathway of pharmaceutical care for breast cancer patients was formulated,and the referral principles of hospitals at different levels and the contents of pharmacist training and assessment were clarified.Results The whole process management pathway of pharmaceutical services for breast cancer patients was developed,including information collection,analysis,evaluation,development implementation of intervention plans,and follow-up.Conclusion This pharmaceutical service pathway can standardize and guide pharmacists in hospitals at different levels to carry out pharmaceutical services for breast cancer patients,achieve the whole process of monitoring drug use,and ensure rational drug use and treatment effectiveness for patients.

For patients with abnormal thyroid function,the detection of peripheral blood coagulation indicators may be irregular,and there is a potential risk of thrombosis or bleeding.Patients with hyperthyroidism have significant endothelial dysfunction and risk of thrombosis.However,the reports on the effect of hypothyroidism on coagulation function are still controversial.The potential risk of abnormal thyroid function to the coagulation system may interfere with the safety of anticoagulant therapy,and the interaction between thyroid disease treatment drugs and anticoagulant drugs also affects the safety of the patient's medication.Therefore,this article is based on previous research literature,analyzes the correlation between abnormal thyroid function and coagulation function,and evaluates and discusses the impact of abnormal thyroid function on the coagulation system and related therapeutic drug interactions.It is expected to provide a reference for diagnosing and treating patients with thyroid dysfunction and abnormal coagulation function.

In January 2023,the American Heart Association(AHA)released A Scientific Statement:Cancer Therapy Related Hypertension,provided an overview of the mechanisms and clinical management of anticancer therapy related hypertension.Contemporary anticancer drugs are mostly at the expense of cardiovascular toxicities,one of the most common side effects is hypertension,especially vascular endothelial growth factor inhibitors,as well as tyrosine kinase inhibitors and proteasome inhibitors.Cancer therapy related hypertension is often dose limiting,and is usually reversible after interruption or discontinuation of treatment.The exact molecular mechanisms underlying hypertension are unclear,recent discoveries indicate an important role for decreased nitric oxide,increased endothelin-1,endothelial dysfunction,increased sympathetic outflow,and microvascular rarefaction.Based on the International Cardio Oncology Society(IC-OS),this article provides an interpretation of the diagnosis and management of hypertension related to cancer treatment.Insufficient evidence exists supporting an antihypertensive medication strategy specific to patients with anticancer therapy induced hypertension,therefore,antihypertensive management should follow current guidelines for the general population..Multidisciplinary cooperation is needed to optimize management to ensure the optimal therapeutic effect from cancer treatment while minimizing competing cardiovascular toxicities.

Objective To evaluate the efficacy of vitamin C intravenous injection in the treatment of patients with sepsis.Methods PubMed,Embase,Scopus,Cochrane Library,and Clinical Trial databases were retrieved,with a retrieval period from database establishment to December 2022.English literatures on randomized controlled trial(RCT)of vitamin C intravenous injection for the treatment of sepsis or septic shock were collected.Meta-analysis was conducted using RevMan 5.3 software and Stata 15.0 software after literature screening,extraction,and evalua-tion of the bias risk included in the studies by two researchers independently.Results A total of 16 RCT studies involving 3 301 patients were included in the analysis.In terms of main outcomes,the 28-day mortality of patients in the vitamin C treatment group was slightly lower than that of the control group,but the difference was not statis-tically significant(RR=0.86,95％CI[0.72-1.03],P=0.10;I2=44％,P=0.10).In terms of secondary out-comes,vitamin C intravenous injection can reduce the duration of vasoactive drug usage time(MD=-23.44,95％CI[-30.53--16.35],P＜0.01;I2=0,P=0.97),but has no significant effect on the 90-day mortality,inten-sive care unit mortality,hospital mortality,duration of mechanical ventilation,difference in estimated sequential organ failure assessment score at 72 hour,length of stay in ICU,and total length of hospital stay of patients(P＞0.05).Conclusion Intravenous vitamin C injection can significantly reduce vasoactive drug usage time,but the available evidence is insufficient to support that intravenous vitamin C can improve the prognosis of patients with sepsis or septic shock.More high-quality,multicenter randomized controlled trial is needed to provide more substantial evidence about the efficacy of vitamin C in treating sepsis or septic shock.

Objective To investigate doctors'knowledge and differences in islet function assessment methods in China.Methods This is a cross-sectional study that conducted by online questionnaire survey.Demographic data,examination items,blood collection point of OGTT,detection method,kit type and follow-up frequency were collected and compared among doctors in different regions,different levels of hospitals,different specialties and different titles.Results 79.2%and 85.1%of physicians believed that the levels of insulin and C-peptide should be measured at the same time to assess islet function in patients with newly diagnosed and follow-up diabetes mellitus patients.Endocrinologists preferred to access insulin and C-peptide at the same time(P<0.05).56.0%of physicians chose bread meal test for T1DM patients and 54.7%for T2DM patients.Compared with non-specialists,endocrinologists preferred to commit bread meal test to T1DM patients(61.4%vs 41.0%,P<0.05).In addition,for the islet function assessment of new-onset diabetes patients,7.6%of physicians chose the six-point method(0,30,60,90,120,180 min),27.3%selected the five-point method I(0,30,60,120,180 min),8.5%selected the five-point method II(0,30,60,90,120 min),9.8%selected the four-point method I(0,30,60,120 min),10.3%selected the four-point method II(0,60,120,180 min),13.8%chose the three-point method(0,60,120 min)and 13.4%chose the two-point method(0,120 min).At the time of follow-up assessment,the above selection rates were 5.3%,20.4%,6.4%,6.6%,9.4%,15.8%and 24.1%,respectively.In terms of the frequency of assessment,39.2%of doctors assessed islet function once a year and 24.7%once every six months.Specialists preferred to assess islet function once a year,and physicians with senior titles chose to assess islet function more variably.Conclusion At present,there are still great differences in assessment methods of islet function in China.It is of great significance for the clinical diagnosis and treatment of diabetes to understand the differences in the selection of islet function assessment methods among doctors in different regions,specialties and job titles.