High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

Traditional Chinese medicine(TCM) decoction pieces are a core carrier for the inheritance and innovation of TCM, and their quality and safety are critical to public health and the sustainable development of the industry. Conventional quality control models, while having established a well-developed system through long-term practice, still face challenges such as relatively long inspection cycles, insufficient objectivity in characterizing complex traits, and urgent needs for improving the efficiency of integrating multidimensional quality information when confronted with the dual demands of large-scale production and precision quality control. With the rapid development of artificial intelligence, machine learning can deeply analyze multidimensional data of the morphology, spectroscopy, and chemical fingerprints of decoction pieces by constructing high-dimensional feature space analysis models, significantly improving the standardization level and decision-making efficiency of quality evaluation. This article reviews the research progress in the application of machine learning in the processing, production, and rapid quality evaluation of TCM decoction pieces. It further analyzes current challenges in technological implementation and proposes potential solutions, offering theoretical and technical references to advance the digital and intelligent transformation of the industry.
Machine Learning ; Drugs, Chinese Herbal/standards* ; Quality Control ; Medicine, Chinese Traditional/standards* ; Humans

OBJECTIVES: With the accelerating aging of the population and the rising prevalence of chronic diseases, the number of patients with pressure injuries (PIs) has increased markedly, prolonging the period of disease-related care. Informal caregivers play a critical role in the daily care of patients with pressure injuries, and their care burden has become increasingly prominent. This study aims to investigate the current status and influencing factors of care burden among informal caregivers of patients with PIs, providing evidence for targeted intervention strategies. METHODS: A total of 170 informal caregivers of patients with PIs were selected by convenience sampling from the Third Xiangya Hospital of Central South University. General demographic and clinical data of both patients and caregivers were collected. The Zarit Caregiver Burden Inventory (ZBI), Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs, General Self-Efficacy Scale (GSES), and Family Caregiver Task Inventory (FCTI) were used to assess caregiving burden, knowledge-attitude-practice level, self-efficacy, and caregiving ability, respectively. Pearson correlation analysis was conducted to evaluate relationships among ZBI, Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs, GSES, and FCTI scores. Stepwise multiple linear regression analysis was used to identify factors influencing caregiving. RESULTS: Among the 170 patients with pressure injuries, the age was (65.52±15.88) years; 118 (69.41%) were male and 52 (30.59%) were female. The duration of PIs was less than 1 month in 108 (63.53%) cases and 1 to 6 months in 40 cases (23.53%). Stage II injuries were predominant (135 cases, 79.41%). A total of 193 pressure injury sites were recorded, most commonly located at the sacrococcygeal region (127 sites, 65.80%), followed by the head (3 sites, 1.55%), shoulder and back (9 sites, 4.66%), feet (24 sites, 12.44%), and other regions (30 sites, 15.55%). Informal caregivers were 48.82% aged 46 to 59 years, 54.71% female, 41.77% primarily spouses and 47.06% children of the patients, and 77.06% lived with the patients. Caregivers who received assistance from others or had higher family per-capita monthly income reported significantly lower caregiver burden scores than those without assistance or with lower income (all P<0.001). The total ZBI score was 50.89±14.95, indicating a moderate burden. The total scores of the Knowledge-Attitude-Practice Scale for Informal Caregivers, GSES, and FCTI were 50.61±7.22, 26.03±7.11, and 14.76±8.70, respectively. Pearson correlation analysis revealed that ZBI scores were correlated with scores on the Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs (r=-0.543, P<0.001), GSES scores (r=-0.545, P<0.001), and FCTI scores (r=0.800, P<0.001). The scores on Knowledge-Attitude-Practice Scale for Informal Caregivers of patients with PIs were correlated with GSES scores (r=0.500, P<0.001) and FCTI scores (r=-0.461, P<0.001); GSES scores was negatively correlated with FCTI scores (r=-0.415, P<0.001). Stepwise multiple linear regression analysis showed that assistance availability, family per-capita monthly income, total scores on the Knowledge-Attitude-Practice Scale for Informal Caregivers of Patients with PIs, total GSES score, and total FCTI score were the main influencing factors of caregiver burden, jointly explaining 79.38% of its variance. CONCLUSIONS The main factors influencing the caregiving burden of informal caregivers of patients with PIs include the availability of assistance, family per-capita monthly income, total score on the Knowledge-Attitude-Practice Scale for Informal Caregivers of PI patients, total score on the GSES, and total score on the FCTI. Developing targeted intervention strategies addressing these factors may help alleviate the caregiving burden among informal caregivers of patients with PIs.
Humans ; Caregivers/psychology* ; Pressure Ulcer/nursing* ; Female ; Male ; Middle Aged ; Cost of Illness ; Adult ; Aged ; Surveys and Questionnaires ; Health Knowledge, Attitudes, Practice ; Self Efficacy ; Caregiver Burden ; China

Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1％)keywords were identified through co-occurrence analysis,including 50(0.3％)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1％)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.

Objective:To investigate the clinical efficacy and safety of ixazomib-containing regimens in the treatment of patients with multiple myeloma(MM).Methods:A retrospective analysis was performed on the clinical efficacy and adverse reactions of 32 MM patients treated with a combined regimen containing ixazomib in the Hematology Department of the First People's Hospital of Lianyungang from January 2020 to February 2022.Among the 32 patients,15 patients were relapsed and refractory multiple myeloma(R/RMM)(R/RMM group),17 patients who responded to bortezomib induction therapy but converted to ixazomib-containing regimen due to adverse events(AE)or other reasons(conversion treatment group).The treatment included IPD regimen(ixazomib+pomalidomide+dexamethasone),IRD regimen(ixazomib+lenalidomide+dexamethasone),ICD regimen(ixazomib+cyclophosphamide+dexamethasone),ID regimen(ixazomib+dexamethasone).Results:Of 15 R/RMM patients,overall response rate(ORR)was 53.3％(8/15),among them,1 achieved complete response(CR),2 achieved very good partial response(VGPR)and 5 achieved partial response(PR).The ORR of the IPD,IRD,ICD and ID regimen group were 100％(3/3),42.9％(3/7),33.3％(1/3),50％(1/2),respectively,there was no statistically significant difference in ORR between four groups(x2=3.375,P=0.452).The ORR of patients was 50％after first-line therapy,42.9％after second line therapy,60％after third line therapy or more,with no statistically significant difference among them(x2=2.164,P=0.730).In conversion treatment group,ORR was 88.2％(15/17),among them,6 patients achieved CR,5 patients achieved VGPR and 4 patients achieved PR.There was no statistically significant difference in ORR between the IPD(100％,3/3),IRD(100％,6/6),ICD(100％,3/3)and ID(60％,3/5)regimen groups(x2=3.737,P=0.184).The median progression-free survival(PFS)time of R/RMM patients was 9 months(95％CI:6.6-11.4 months),the median overall survival(OS)time was 18 months(95％CI:11.8-24.4 months).The median PFS time of conversion treatment group was 15 months(95％CI:7.3-22.7 months),the median OS time not reached.A total of 10 patients suffered grade 3-4 adverse event(AE).The common hematological toxicities were leukocytopenia,anemia,thrombocytopenia.The common non-hematological toxicities were gastrointestinal symptoms(diarrhea,nausea and vomit),peripheral neuropathy,fatigue and infections.Grade 1-2 peripheral neurotoxicity occurred in 7 patients.Conclusion:The ixazomib-based chemotherapy regimens are safe and effective in R/RMM therapy,particularly for conversion patients who are effective for bortezomib therapy.The AE was manageable and safe.

Additive manufacturing(3D printing)technology aligns with the direction of precision and customization in future medicine,presenting a significant opportunity for innovative development in high-end medical devices.Currently,research and industrialization of 3D printed medical devices mainly focus on nondegradable implants and degradable implants.Primary areas including metallic orthopaedic implants,polyether-ether-ketone(PEEK)bone implants,and biodegradable implants have been developed for clinical and industrial application.Recent research achievements in these areas are reviewed,with a discussion on the additive manufacturing technologies and applications for customized implants.Challenges faced by different types of implants are analyzed from technological,application,and regulatory perspectives.Furthermore,prospects and suggestions for future development are outlined.

Background::The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE.Methods::In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.Results::The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243–5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056–5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792–30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467–8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288–36.484) were independently associated with elevated hs-cTnI. Conclusions::CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

In this study, CM-5 spectrophotometer and Heracles NEO ultra-fast gas-phase electronic nose were used to analyze the changes in color and odor of vinegar-processed Cyperi Rhizoma(VPCR) pieces. Various analysis methods such as DFA and partial least squares discriminant analysis(PLS-DA) were combined to identify different processing degrees and quantify the end point of processing. The results showed that with the increase in vinegar processing, the brightness parameter L~* of VPCR pieces decreased gradua-lly, while the red-green value a~* and yellow-blue value b~* initially increased and reached their maximum at 8 min of processing, followed by a gradual decrease. A discriminant model based on the color parameters L~*, a~*, and b~* was established(with a discrimination accuracy of 98.5%), which effectively differentiated different degrees of VPCR pieces. Using the electronic nose, 26 odor components were identified from VPCR samples at different degrees of vinegar processing. DFA and PLS-DA models were established for different degrees of VPCR pieces. The results showed that the 8-min processed samples were significantly distinct from other samples. Based on variable importance in projection(VIP) value greater than 1, 10 odor components, including 3-methylfuran, 2-methylbuty-raldehyde, 2-methylpropionic acid, furfural, and α-pinene, were selected as odor markers for differentiating the degrees of vinegar processing in VPCR. By combining the changes in color and the characteristic odor components, the optimal processing time for VPCR was determined to be 8 min. This study provided a scientific basis for the standardization of vinegar processing techniques for VPCR and the improvement of its quality standards and also offered new methods and ideas for the rapid identification and quality control of the end point of processing for other traditional Chinese medicine.
Acetic Acid ; Drugs, Chinese Herbal/analysis* ; Rhizome/chemistry* ; Quality Control ; Electronics

On the basis of the qualitative preparation quality markers of Zhibao Sanbian Wan (ZBSBW), we screened out the quantitative markers and evaluated the content consistency of ZBSBW. A method capable of simultaneously determining 34 compounds in ZBSBW was established based on HPLC-MS/MS, and 16 batches of ZBSBW were simultaneously analyzed by this method. Furthermore, we explored a general strategy for analyzing the component migration in preparation, plasma, brain tissue and cerebrospinal fluid. The methodological investigation was confirmed by linear range, recovery (85.10%-105.07%), precision (RSD: 1.37%-4.58%), stability, and repeatability (3.00%-12.45%), the established method was suitable for the detection and quantification of the compounds in ZBSBW. The contents of compounds in ZBSBW were all lower than 1 mg·g^-1, and the contents and daily dose of nystose were the highest, followed by echinacoside, paeoniflorin, osthole and paeonol. The results of systematic clustering showed that the contents were consistent for ordinary preparations of ZBSBW. The principal component analysis showed that the components of berberine, ginsenoside Re, ginsenoside Rg1, pinoresinol diglucoside and tenuifolin had large variation, which contributed significantly to the grouping. The contents of echinacoside, verbascoside, polygalaxanthone Ⅲ, β-ecdysterone, osthole, alisol B 23-acetate, liquiritin and glycyrrhizic acid were stable from batch to batch. The animal experiment results showed that osthole, paeonol and liquiritin in ZBSBW could be absorbed into the blood and enter the brain tissue by passing through the blood-brain barrier. All animal studies were reviewed and approved by the Institutional Animal Care and Use Committee at Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences (No. 2020B071). The above compounds contributed the quantitative preparation quality markers of ZBSBW. In conclusion, the HPLC-MS/MS method established in this study was sensitive, accurate and rapid, and could be used for simultaneous quantification of 34 compounds and content consistency evaluation of multiple batches of preparations in ZBSBW. The result provided a methodological basis for the screening of quantitative preparation quality markers and material basis research of ZBSBW.

Objective: To explore a simple and feasible method for the isolation and purification of hepatocytes, hepatic stellate cells (HSC), and lymphocytes from mice. Methods: The cell suspension was obtained from male C57bl/6 mice by hepatic perfusion through the portal vein digestion method and then isolated and purified by discontinuous Percoll gradient centrifugation. Trypan blue exclusion was used to determine cell viability. Glycogen staining, cytokeratin 18, and transmission electron microscopy were used to identify hepatic cells. Immunofluorescence was used to detect α-smooth muscle actin combined with desmin in HSCs. Flow cytometry was used to analyze lymphocyte subsets in the liver. Results: After isolation and purification, about 2.7×10(7) hepatocytes, 5.7×10(5) HSCS, and 4.6×106 hepatic mononuclear cells were obtained from the liver of mice with a body weight of about 22g. The cell survival rate in each group was > 95%. Hepatocytes were apparent in glycogen deposited purple-red granules and cytokeratin 18. Electron microscopy showed that there were abundant organelles in hepatocytes and tight junctions between cells. HSC had expressed α-smooth muscle actin and desmin. Flow cytometry showed hepatic mononuclear cells, including lymphocyte subsets such as CD4, CD8, NKs, and NKTs. Conclusion: The hepatic perfusion through the portal vein digestion method can isolate multiple primary cells from the liver of mice at once and has the features of simplicity and efficiency.
Male ; Mice ; Animals ; Keratin-18 ; Actins ; Desmin ; Liver ; Hepatocytes ; Hepatic Stellate Cells