ObjectiveTaking the cuproptosis/oxidative stress pathway as the entry point， this study investigated the effect and mechanism of Liangyi Paste on hepatic lipid deposition in naturally aged mice fed with a high-fat diet. MethodsAfter adaptive feeding， 80 ten-week-old male C57BL/6 mice were used. Thirty of them were randomly divided into three groups （10 mice per group）： The 12-month-old control group （12MCON）， the 15-month-old control group （15MCON）， and the 15-month-old group with a high-fat diet （15MHFD）. The 12MCON and 15MCON groups were continuously fed a standard diet， while the 15MHFD group started receiving a high-fat diet at 12 months of age. Tissue samples were collected at the corresponding time points for each group. The remaining 50 mice were randomly divided into five groups （10 mice per group）： the 20-month-old control group （20MCON）， the model group， and the low-， medium-， and high-dose Liangyi Paste groups （2.91 ， 5.82 ， 11.64 g·kg^-1·d^-1， respectively）. The 20MCON group was continuously fed a standard diet， while the other groups started receiving a high-fat diet at 15 months of age. At 18 months of age， the Liangyi Paste groups were administered the corresponding doses of Liangyi Paste by gavage， while the 20MCON and model groups were given an equal volume of saline by gavage. After 8 weeks of continuous gavage （when the mice reached 20 months of age）， tissue samples were collected. Hepatic TG levels were measured using assay kits； liver histology and lipid deposition were observed via hematoxylin-eosin （HE） and oil red O staining； reactive oxygen species （ROS） were detected by enzyme-linked immunosorbent assay （ELISA）； Cu²⁺， superoxide dismutase （SOD）， and malondialdehyde （MDA） levels were measured by colorimetry； mRNA and protein expression of genes related to cuproptosis and oxidative stress pathways were analyzed by Real-time polymerase chain reaction（Real-time PCR） and Wes automated protein expression system. ResultsCompared with 12MCON， the 15MCON group showed significantly increased hepatic TG， Cu²⁺， ROS， and MDA levels （P<0.01）， decreased SOD （P<0.01）， hepatocyte swelling， and disordered arrangement. The mRNA and protein levels of ferredoxin 1 （FDX1）， dihydrolipoamide S-acetyltransferase （DLAT）， heat shock protein 70 （HSP70）， dihydrolipoamide dehydrogenase （DLD）， pyruvate dehydrogenase E1 subunit-β （PDHB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and peroxisome proliferator-activated receptor γ （PPARγ） were significantly elevated （P<0.05， P<0.01）. Compared with 15MCON group， the 15MHFD and 20MCON groups exhibited further increases in TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， and aggravated hepatocyte swelling and disorder. There were increased lipid droplets with mild vacuolization in the 15MHFD group， and no significant lipid deposition was observed in the 20MCON group. FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and protein levels were significantly increased （P<0.05， P<0.01）. Compared with 20MCON group， the model group demonstrated markedly elevated TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， severe hepatic steatosis， and upregulated expression of FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and proteins （P<0.05， P<0.01）. All abnormalities were significantly reversed after Liangyi Paste treatment. ConclusionLiangyi paste can ameliorate hepatic lipid deposition in naturally aged mice with a high-fat diet by modulating the cuproptosis/oxidative stress pathway.

Objective To evaluate the dissolution effects of pediatric ammonium urate stones in solutions with different pH values, so as to provide reference for the clinical treatment of this type of stones. Methods Eight pure ammonium urate stones(ammonium urate content ≥90%)of similar size and mass(median mass 4.6 g)were obtained from 8 children(＜14 years)undergoing percutaneous nephrolithotomy at the People's Hospital of Xinjiang Uygur Autonomous Region. The stones were placed in sodium chloride solutions with pH values of 5.0, 6.0, 7.0, and 8.5 and artificial urine with pH values of 4. 6, 5.0, 7.0, and 8.5 at a constant temperature of 37 ℃. The mass of the stones was recorded before placement and at 24, 48, and 72 h after placement. The dissolution rates of the stones were calculated. Results The pediatric ammonium urate stones could be dissolved in sodium chloride solution, and the total dissolution rate was the highest(94.6%)after 72 hours when the pH value was 6.0. The total dissolution rate of ammonium urate stones in artificial urine after 72 hours were all over 50%, and the total dissolution rate was the highest(79.7%)when the pH value was 4.6. Conclusion Pediatric ammonium urate stones are soluble in sodium chloride solution and artificial urine, and the total dissolution rate is higher in acidic environment.

Objective To design a high altitude adaptive oxygen generator for the crews to alleviate their high altitude reaction in high altitude environment and meet their requirements for oxygen supply.Methods A high altitude adaptive oxygen generator based on the mature pressure swing adsorption oxygen production method was designed with the key technologies of discharge capacity compensation of air compression pump and airway fusion of molecular sieve tower,which had the components of molecular sieve tower,air compression pump,controller,cooling fan,cooler,solenoid valve,regulator,flow meter and etc.Trials were carried out at the simulated altitude and field plateau environment so as to verify the high altitude adaptive performance of the oxygen generator developed.Results The trial results showed the oxygen generator met the desired objectives and the requirements for oxygen volume fraction in GJB 2799-1996 General specification for medical oxygen generator using molecular sieve method.Conclusion The oxygen generartor provides oxygen supply effectively for vehicle operators in plateau environments or the ones rushing into the plateau.[Chinese Medical Equipment Journal,2025,46(4):29-34]

Hot melt extrusion(HME)technology employs thermodynamic and kinetic principles to mix pharmaceutical polymers with crystalline drugs at high temperatures and extrude them,embedding drug molecules within the polymer matrix to form solid dispersions.Due to its solvent-free nature,capability for one-step processing,and support for continuous operation,HME has garnered significant attention in the pharmaceutical industry in recent years.This article introduced the basic principles and development history of HME technology and its marketed drugs.It reviewed the research progress of HME technology in improving drug solubility,masking taste,controlled release,targeted release,oral dispersible films,implant formulations,semi-solid formulations,and 3D printed formulations.Additionally,the article summarized the advantages and limitations of HME technology and provided an outlook on its future development.

BACKGROUND:Knee finite element modelling can provide insight into knee mechanics,but its complex image segmentation is more difficult for researchers.With the development of deep learning techniques,deep learning techniques have been widely used in knee joint finite element modelling.OBJECTIVE:To replace the manual segmentation step in finite element modelling of the knee joint by using 3D Swin UNETR in combination with a semi-automatic segmentation technique for statistical shape models.METHODS:Manual(artificial)knee joint finite element model was developed based on MR and semi-automatic knee joint finite element model was developed based on 3D Swin UNETR+statistical shape model segmentation.The same loads and boundary conditions were applied to both models.Validation was performed by calculating the Dice similarity coefficient,mean distance,and comparing the peak equivalent stresses,maximum principal stresses,and maximum shear stresses of the two models.RESULTS AND CONCLUSION:(1)The Dice similarity coefficients of the manual and semi-automatic segmented femur and tibia were more than 98％,and the average distances were less than or equal to(0.35±0.08)mm.(2)With the longitudinal load of 750 N and 10 Nm internal overturning moment applied to the femur tip of both manual and semi-automatic finite element models,the peak equivalent stress,maximum principal stress,and maximum shear stresses of meniscus in manual finite element model were 14.12,18.54,and 7.35 MPa;peak equivalent force,maximum principal stress,and maximum shear stress of femoral cartilage were 2.22,2.15,and 1.18 MPa;peak equivalent force,maximum principal stress,and maximum shear stress of tibial cartilage were 2.50,1.91,and 1.41 MPa;semi-automatic finite element model of meniscus:peak equivalent force,maximum principal stress,and maximum shear stress were 14.93,18.53,and 7.75 MPa.The peak equivalent force,maximum principal stress,and maximum shear stress of femoral cartilage were 2.26,2.18,and 1.20 MPa;the peak equivalent stress,maximum principal stress,and maximum shear stress of tibial cartilage were 2.60,1.91,and 1.46 MPa.The peak equivalent stress,maximum principal stress,and maximum shear stress of manual and semi-automatic finite element models were basically consistent,with no significant difference(P＞0.05).(3)The semi-automatic segmentation technique proposed in this study can replace manual segmentation in creating accurate finite element models of the knee joint.

Objective Based on apolipoprotein a-Ⅰ(Apoa-Ⅰ)gene knockout mice,the role and mechanism of phosphotidylcholine(PC)in improving cholesterol reverse transport were explored.Methods Thirty Apoa-Ⅰ-/-mice were randomly divided into an Apoa-Ⅰ-/-group,Apoa-Ⅰ-/-+HFD group,and Apoa-Ⅰ-/-+HFD+PC group using the random number table method;30 C57BL/6J mice were randomly divided into a WT group,WT+HFD group,and WT+HFD+PC control groups,with 10 mice in each group.The Apoa-Ⅰ-/-group and WT groups were fed basic feed,while the other groups were fed high-fat feed for 8 weeks to establish a hyperlipidemia model.From the 9th week,the WT+HFD+PC group and Apoa-Ⅰ-/-+HFD+PC group were given PC 2.5 g/(kg·d),while the remaining mice were given physiological saline by gavage for a total of 4 weeks of intervention.The serum lipid levels of the mice were detected using a fully automated analyzer.Hematoxylin and eosin and Oil red O staining were used to observe pathological and morphological changes,and the COD-PAP method was used to detect cholesterol levels in mouse liver tissue.The ELISA method was used to detect LCTA levels in mouse serum,and RT-qPCR and Western Blot method were used to detect the mRNA and protein expression of cholesterol ATP binding cassette transporter A1(ABCA1),ATP binding cassette transporter G1(ABC A1),lecithin cholesterol acyltransferase(LCAT),hepatic lipase(HL),scavenger receptor class B type Ⅰ(SR-B1),and low-density lipoprotein receptor(LDL-R)in liver tissue.Results Compared with the WT group,the serum lipid levelsof WT+HFD group mice were significantly increased(P＜0.01),LCAT levels were significantly reduced(P＜0.05),hepatic fat vacuoles were obvious,hepatic lipid deposition was significant,and liver tissue TC levels were significantly increased(P＜0.01).The mRNA and protein expression of ABCA1,ABCG1,LCAT,SR-B1,HL,and LDL-R were significantly reduced(P＜0.05,P＜0.01).Compared with the WT+HFD group,serum lipid levels in the WT+HFD+PC group were significantly reduced(P＜0.05,P＜0.01),LCAT levels were significantly increased(P＜0.05),hepatic fat vacuoles were significantly reduced,hepatic lipid deposition was alleviated,and liver tissue TC levels were significantly reduced(P＜0.05);mRNA and protein expression of ABCA1,LCAT,SR-B1,HL and LDL-R were significantly increased(P＜0.05,P＜0.01).The serum levels of TC,TG,and LDL-C were significantly increased,while the levels of LCAT、HDL-C were significantly reduced(P＜0.05,P＜0.01)in the Apoa-Ⅰ-/-+HFD group mice.Hepatocytes underwent balloon-like transformation,liver lipid deposition was significantly aggravated,and liver tissue TC levels were significantly increased(P＜0.05).The mRNA and protein expression of ABCA1,LCAT and HL were significantly reduced(P＜0.05,P＜0.01).Compared with the WT+HFD+PC group mice,the Apoa-Ⅰ-/-+HFD+PC group mice showed a significant increase in serum lipid levels(P＜0.05,P＜0.01),LCAT levels were significantly reduced(P＜0.05),significant hepatic lipid vacuoles,significant hepatic lipid deposition,and a significant increase in TC levels in liver tissue(P＜0.05).Their mRNA and protein expression of ABCA1,ABCG1,LCAT,SR-B1,and HL were also significantly reduced(P＜0.05,P＜0.01).Conclusions Phosphatidylcholine can improve dyslipidemia by interfering with Apoa-Ⅰ and thus regulating cholesterol reverse transport.

Advances in genomics,biochemistry,and genetics have deepened our understanding of epigenetic mechanisms.These mechanisms play a crucial role in life,heredity,and evo-lution.Their growing significance is driving biomedical research toward personalized and precise medicine.Renal diseases,par-ticularly chronic kidney disease and acute kidney injury,require new treatment strategies.Their subtle clinical symptoms and challenges in early diagnosis limit current therapeutic options.Research on epigenetic modifications in renal diseases is expan-ding rapidly.This field is emerging as a promising approach for kidney disease treatment.The transition from basic mechanistic studies to clinical applications is underway.Epigenetic modifica-tions hold great potential for improving early diagnosis,enabling personalized treatment,and advancing precision medicine in re-nal diseases.

Objective To identify the taste critical quality attribute and design and optimize the flavor-correcting formulation of the traditional Chinese medicine oral preparation Qingre Jiedu Oral Liquid,in order to improve its taste and enhance patient medication adherence.Methods The taste assignment method was employed to identify the taste critical quality attribute of Qingre Jiedu Oral Liquid.Based on human sensory evaluation and the standardized Euclidean distance in electronic tongue analysis,suitable types of corrigent were determined.Subsequently,under constraints such as maximum allowable dosage,solubility,and sweetness,the optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined using Box-Behnken experimental design combined with electronic tongue and human sensory evaluation results.The study was reviewed and approved by the Ethics Committee of Beijing University of Chinese Medicine(Ethics Approval Number 2020BZYLL0609).Results The quantitative score for bitter taste of Qingre Jiedu Oral Liquid accounted for 30.36%,confirming bitterness as the taste critical quality attribute requiring attention.The optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined to be 120 mg·mL?1 erythritol,12 mg·mL?1 acesulfame potassium,and 2.4 mg·mL?1 stevioside.This formulation achieved an 11.75-point improvement in sensory evaluation scores compared to the original commercially available oral liquid.Conclusion This study successfully improved the taste of Qingre Jiedu Oral Liquid and established a comprehensive strategy for flavor-correcting formulation optimization,including a method for identifying taste critical quality attribute.This strategy provides a referential paradigm for palatability enhancement of similar traditional Chinese medicine oral preparations,laying a crucial technical foundation for elevating the clinical value of Chinese herbal medicines and promoting the high-quality development of traditional Chinese medicine(TCM).

Advances in genomics,biochemistry,and genetics have deepened our understanding of epigenetic mechanisms.These mechanisms play a crucial role in life,heredity,and evo-lution.Their growing significance is driving biomedical research toward personalized and precise medicine.Renal diseases,par-ticularly chronic kidney disease and acute kidney injury,require new treatment strategies.Their subtle clinical symptoms and challenges in early diagnosis limit current therapeutic options.Research on epigenetic modifications in renal diseases is expan-ding rapidly.This field is emerging as a promising approach for kidney disease treatment.The transition from basic mechanistic studies to clinical applications is underway.Epigenetic modifica-tions hold great potential for improving early diagnosis,enabling personalized treatment,and advancing precision medicine in re-nal diseases.

Objective To identify the taste critical quality attribute and design and optimize the flavor-correcting formulation of the traditional Chinese medicine oral preparation Qingre Jiedu Oral Liquid,in order to improve its taste and enhance patient medication adherence.Methods The taste assignment method was employed to identify the taste critical quality attribute of Qingre Jiedu Oral Liquid.Based on human sensory evaluation and the standardized Euclidean distance in electronic tongue analysis,suitable types of corrigent were determined.Subsequently,under constraints such as maximum allowable dosage,solubility,and sweetness,the optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined using Box-Behnken experimental design combined with electronic tongue and human sensory evaluation results.The study was reviewed and approved by the Ethics Committee of Beijing University of Chinese Medicine(Ethics Approval Number 2020BZYLL0609).Results The quantitative score for bitter taste of Qingre Jiedu Oral Liquid accounted for 30.36%,confirming bitterness as the taste critical quality attribute requiring attention.The optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined to be 120 mg·mL?1 erythritol,12 mg·mL?1 acesulfame potassium,and 2.4 mg·mL?1 stevioside.This formulation achieved an 11.75-point improvement in sensory evaluation scores compared to the original commercially available oral liquid.Conclusion This study successfully improved the taste of Qingre Jiedu Oral Liquid and established a comprehensive strategy for flavor-correcting formulation optimization,including a method for identifying taste critical quality attribute.This strategy provides a referential paradigm for palatability enhancement of similar traditional Chinese medicine oral preparations,laying a crucial technical foundation for elevating the clinical value of Chinese herbal medicines and promoting the high-quality development of traditional Chinese medicine(TCM).