ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

To systematically evaluate the impact of the "group-based " medical assistance program for Xizang, conducted by Peking Union Medical College Hospital, on the implementation outcomes of standardized residency training (SRT) at the Xizang Autonomous Region People′s Hospital, and to provide evidence-based decision-making references and policy optimization recommendations for medical education support models in border ethnic minority regions.

Objective To investigate the effect and mechnism of betaine(BET)in reversing chemotherapy resistance in prostate cancer(PCa)by inhibiting ATP-binding cassette subfamily B member 1(ABCB1).Methods The PCa chemotherapy-sensitive C4-2B cells were cultured,and the TaxR cells resistant to docetaxel(DTX)were established by gradient increase the concentration of DTX.The drug resistance of C4-2B and TaxR cells against DTX was assessed using CCK-8 and the colony formation experiment.Western blotting and qRT-PCR were used to detect ABCB1 expression.The TaxR cells were divided into:(1)Control group,negative control group(NC),siABCB1-1 group(transfected with siABCB1-1),and siABCB1-2 group(transfected with siABCB1-2).Western blotting was used to detect the effect of small interfering RNA on silencing ABCB1,and CCK-8 was used to detect the differences in DTX resistance between each group.(2)Different concentrations of BET(0,100,200,400,600,800 mmol/L)groups.These groups were subjected to CCK-8 to detect cell viability,and Western blotting was used to detect the protein expression of ABCB1.(3)Control group,DTX group(20 nmol/L DTX),BET group(200 mmol/L BET),and DTX+BET group(20 nmol/L DTX+200 mmol/L BET),flow cytometry was used to detect apoptosis rate and cell cycle,and Western blotting to detect the protein expression of apoptosis-related proteins(Bcl2,BAX,c-caspase-3).(4)Control group,BET group(200 mmol/L BET),wortmannin(WM)group(100 μmol/L WM),and BET+WM group(200 mmol/L BET+100 μmol/L WM).Western blotting was used to detect the protein expression of PI3K,Akt,and ABCB1.(5)Control group,BET group(200 mmol/L BET),and BAY group(10 μmol/L BAY),BAY+BET group(200 mmol/L BET+10 μmol/L BAY).Western blotting was used to detect the protein expression of NF-κB p65,p-ikBα and ABCB1.Network pharmacology combined with transcriptome sequencing was used to predict the possible pathways for BET to reverse chemotherapy resistance.Results Compared with C4-2B cells,TaxR cells showed significantly increased resistance to DTX(P<0.01),and high expression of ABCB1(P<0.01).After silencing ABCB1 with siRNA,TaxR cells'resistance to DTX was significantly inhibited(P<0.01).The inhibition rate of TaxR cells treated with 200 mmol/L BET was less than 20%,and it significantly decreased the expression of ABCB1 protein in TaxR cells(P<0.05).Compared with control group,the combination of 200 mmol/L BET and 20 nmol/L DTX resulted in higher apoptosis rate and higher S stage cell ratio,lower expression of Bcl-2 protein and higher expression of BAX and c-caspase-3 proteins than the two drugs used alone(P<0.05).Compared with control group,the combination of 200 mmol/L BET and 100 μmol/L WM significantly down-regulated the protein expression of PI3K,Akt and ABCB1(P<0.01).The combination of 200 mmol/L BET and 10 μmol/L BAY significantly down-regulated the protein expression of NF-κB p65,p-ikBα and ABCB1(P<0.01).Conclusion BET may reverse TaxR cells'chemotherapy resistance by down-regulating ABCB1 expression through the PI3K/Akt/NF-κB signaling pathway.

Objective To explore the pathogenesis of Alzheimer's disease by examining the effects of dihydroartemisinin(DHA)on cognitive behavior,hippocampal,cerebral cortex and retinal cell morphology,β-amyloid(Aβ)and autophagy-related proteins in 5×FAD mice.Methods Twenty 5×FAD mice and 5 wild type(WT)mice were selected,all of which were female.The 5×FAD mice were randomly divided into model(M)group,donepezil(D)group,low-dose DHA(DHA-L)group,and high-dose DHA(DHA-H)group.The WT and M groups were not treated,and the D group was given donepezil 0.1 mg/kg per day.DHA-L group and DHA-H group were given 10 mg/kg and 20 mg/kg DHA per day,respectively.Group D,group DHA-L and group DHA-H were given intragastric administration once a day for 3 months.The changes of in cognitive behavior were measured by Morris experiment.HE staining was used to observe the arrangement and morphology of nerve cells in cerebral cortex,hippocampus and retina.The expressions of Aβ protein in cerebral cortex,hippocampus and retina were detected by immunohistochemistry.Western blotting detected the expression of autophagy related proteins(LC3-Ⅰ,LC3-Ⅱ,Beclin-1,P62,β-actin).Results The DHA-H group and the D group exhibited more frequent adoption of both linear and trending exploration routes.Compared to the model group,significant differences in the contents of Aβ in the hippocampal CA1,cerebral cortex S1,and retinal were observed(P＜0.0001)in the other four groups.The analysis also showed significant differences in autophagy-associated proteins between the DHA-L,DHA-H,and model groups(P＜0.01).Conclusion DHA improves cognitive function and increases the number of nerve cells in mice.It also reduces Aβ content in the cerebral cortex,hippocampus,and retina,along with improving autophagy-associated protein deposition in mice.

Objective To evaluate the therapeutic effects of different intracranial pressure lower-ing regimens in patients with acute large-area cerebral infarction based on electrical impedance tomo-graphy(EIT)technology.Methods A total of 75 patients with acute large-area cerebral infarction were selected as the study subjects and randomly divided into study group(n=40,using mannitol combined with albumin to decrease intracranial pressure)and control group(n=35,using mannitol alone to decrease intracranial pressure).EIT technology was used to continuously monitor the changes in intracranial pressure within 48 hours in the patients.Clinical data of the two groups were collected,and the 24-hour intracranial pressure change rate,48-hour intracranial pressure change rate,ICU stay duration,hospitalization duration,antibiotic use duration,and National Institutes of Health Stroke Scale(NIHSS)score at discharge were observed and compared between the two groups.A 90-day sur-vival follow-up was also conducted.Results There was no statistically significant difference in the 24-hour intracranial pressure change rate between the two groups(P＞0.05).The 48-hour intracrani-al pressure change rate in the study group was higher than that in the control group,and the difference was statistically significant(P＜0.05).The ICU stay duration,hospitalization duration,and antibiotic use duration in the study group were all shorter than those in the control group,and the NIHSS score at discharge in the study group was lower than that in the control group,with statistically significant differences(P＜0.05).The follow-up results showed that the survival duration in the study group was longer than that in the control group,and the 90-day cumulative survival rate in the study group was higher than that in the control group,but the differences were not statistically significant(P＞0.05).The modified Rankin Scale score in the study group was lower than that in the control group,and the difference was statistically significant(P＜0.05).Conclusion Compared with the use of mannitol alone,early use of mannitol combined with albumin can effectively decrease the in-tracranial pressure within 48 hours,shorten the hospitalization duration,and improve neurological function in patients with acute large-area cerebral infarction.

Objective:To optimize the image quality of PET/CT following 90Y-selective internal radiation therapy ( 90Y-SIRT) using block-sequential regularized expectation maximization (BSREM) reconstruction algorithm, and to evaluate its impact of different β values on image quality and quantitative analysis. Methods:A retrospective study was conducted on 8 male patients with hepatic tumors (age: 62(52, 71) years) treated at Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine Tsinghua University, between June 2024 and January 2025. All patients were treated with 90Y resin microspheres (2.6(0.9, 3.6)GBq) and underwent post-treatment 90Y PET/CT liver imaging. Imaging data were reconstructed using BSREM with different noise penalty weighting factors ( β values: 0, 300, 1000, 1500, 2500, 3500, 4000, 6000, 8000, 10000). Visual assessment was independently performed by two nuclear medicine physicians, using a 4-point scale (1=worst, 4=best). The mean score was considered as the final score. The consistency of the 2 reviewers was calculated and analyzed by Kappa test. Visual scores of different β value groups were compared by Friedman test. The β value demonstrating highest mean score and optimal consistency was selected as the optimal. Quantitative analysis was performed using MIM software to calculate the maximum absorbed dose ( Dmax) and the mean absorbed dose ( Dmean) for tumor, normal liver, and whole liver regions, and the CV was used to evaluate the impact of β values. Results:The visual assessment consistency of reviewers in 3 β value groups (0, 3500, 6000) were the highest (7/8) (all kappa=0.88, all P<0.05). Visual scores of the 10 β value groups were significantly different ( χ2=28.74, P<0.001), and the visual scores of 2 β value groups (3500, 4000) were the highest, both of which were 4.0(4.0, 4.0). Overall, visual assessment identified β=3500 as the optimal. Quantitative analysis revealed that, (1) Dmax in all regions (tumor, normal liver, whole liver) decreased with the increasing β values, stabilizing when β>1000 ( CV 56%-67%); (2) Dmean remained stable across different β values ( CV 0.04%-5.00%). Conclusions:In BSREM reconstruction, β=3500 is the optimal parameter for improving 90Y-PET image quality. β values significantly affect Dmax (stabilizing at β > 1000), but have no significant impact on Dmean, suggesting that reconstruction parameters primarily influence dose distribution morphology rather than average dose assessments.

Objective To explore the distribution and characteristics of traditional Chinese medicine(TCM)syndromes in patients with adenomyosis.Methods A retrospective analysis was conducted on the data collected from patients with adenomyosis between December 2019 and April 2022 based on a cross-sectional survey.Variables included age,body mass index(BMI),disease duration,geographical region,dysmenorrhea,menstrual flow,diagnosis and treatment goals,history of adenomyosis-related surgery,postoperative recurrence,and carbohydrate antigen 125(CA125)and carbohydrate antigen 199(CA199)levels.The distribution pattern of TCM syndromes,including general information of patients with different syndromes,CA125 and CA199 levels,were analyzed.The relationship between syndromes and age,BMI,duration of disease,geographic region,and history of adenomyosis-related surgery were analyzed using the multinomial logistic regression.Results A total of 1,816 patients with adenomyosis were included.The most common TCM syndrome was syndrome of cold coagulation and blood stasis(36.84%).The other four TCM syndromes,ranked by frequency,were syndrome of qi stagnation and blood stasis(25.39%),syndrome of blood stasis due to qi deficiency(17.35%),syndrome of kidney deficiency and blood stasis(15.97%),and syndrome of intermin-gled phlegm and blood stasis(4.46%).Significant differences in age,disease duration,and BMI were observed among patients with different TCM syndromes(P<0.05).Patients with syndrome of cold congelation and blood stasis,syndrome of kidney deficiency and blood stasis,were younger than those with syndrome of qi stagnation and blood stasis.Patients with syndrome of cold congelation and blood stasis had a longer disease duration than those with syndrome of blood stasis due to qi deficiency.Patients with syndrome of blood stasis due to qi deficiency had lower BMI(P<0.05)than those with syndrome of intermin-gled phlegm and blood stasis.The most common symptom in North China,East China,Southwest China,Northwest China,and Northeast China was syndrome of cold congelation and blood stasis,accounting for 45.39%,35.98%,30.33%,41.38%,and 50.00%,respectively.The most common syndrome in Southern and Central China was syndrome of qi stagnation and blood stasis,accounting for 31.34%and 36.23%respectively.Differences in syndrome distribution were observed between patients in East,Southwest,South,and Central China and those in North China(P<0.05).Syndrome distribution also varied significantly across different diagnosis and treatment goals,as well as menstrual conditions(P<0.05).For treatment goals such as pain relief,lesion control,menstrual flow reduction,and recurrence prevention,the dominant syndromes were syndrome of cold congelation and blood stasis(40.67%,37.13%,36.95%,and 43.35%,respectively)and syndrome of qi stagnation and blood stasis(29.35%,26.39%,26.10%,and 25.75%,respectively).Among patients seeking assisted pregnancy,the primary syndromes were syndrome of cold congelation and blood stasis(41.12%)and syndrome of kidney deficiency and blood stasis(18.69%).Patients with dysmenorrhea were mostly diagnosed with syndrome of cold congelation and blood stasis(39.95%)and syndrome of qi stagnation and blood stasis(28.52%).Differences in syndrome distribution were observed between patients with small and large menstrual volume,with a higher proportion of syndrome of kidney deficiency and blood stasis in patients with small menstrual volume(P<0.05).However,no significant difference was noted in the distribution of TCM syndromes in different treatment stages.Additionally,no statistical significance was observed in the CA125 and CA199 levels among patients with various TCM syndromes.Multinomial logistic regression analysis revealed that compared with syndrome of cold congelation and blood stasis,the course of disease was the influencing factor of syndrome of blood stasis due to qi deficiency,BMI was the influencing factor of syndrome of qi stagnation and blood stasis and syndrome of intermin-gled phlegm and blood stasis,and geography was the influencing factor of syndrome of blood stasis due to qi deficiency,syndrome of qi stagnation and blood stasis,syndrome of kidney deficiency and blood stasis,and syndrome of intermin-gled phlegm and blood stasis.Conclusion Syndrome of cold coagulation and blood stasis is the most prevalent TCM syndrome among patients with adenomyosis,and the distribution of TCM syndromes has a specific regularity.The syndromes are independently correlated with region,disease duration,and BMI.

OBJECTIVE: The analgesic effect of acupuncture has been widely accepted. Nevertheless, the mechanism behind its analgesic effect remains elusive, thus impeding the progress of research geared toward enhancing the analgesic effect of acupuncture. This paper investigated the role of acupuncture needle surface textures on acupuncture's analgesic effect by creating four experimental acupuncture needles with different patterns of surface augmentation. METHODS: Four types of acupuncture needles with different surface textures (the lined needle, circle needle, sandpaper needle, and threaded needle) were designed. Additionally, the force/torque measurement system used a robot arm and mechanical sensor to measure the force on the needle during insertion and manipulation. To perform acupuncture analgesia experiments, four experimental acupuncture needles and a normal needle were inserted into the Zusanli (ST36) acupoint of rats with inflammatory pain. By comparing the force and torque and the analgesic efficacy of the different acupuncture needles, these experiments tested the role of acupuncture needle body texture on acupuncture analgesia. RESULTS: The analgesic effects of different acupuncture needle body textures varied. Specifically, the force required to penetrate the skin with the lined needle was not greater than that for the normal needle; however, the needle with inscribed circles and the sandpaper-roughened needle both required greater force for insertion. Additionally, the torque of the lined needle reached 2 × 10^-4 N·m under twisting manipulation, which was four times greater the torque of a normal needle (5 × 10^-5 N·m). Furthermore, the lined needle improved pain threshold and mast cell degranulation rate compared to the normal needle. CONCLUSION Optimizing the texture of acupuncture needles can enhance acupuncture analgesia. The texture of our experimental acupuncture needles had a significant impact on the force needed to penetrate the skin and the torque needed to manipulate the needle; it was also linked to variable analgesic effects. This study provides a theoretical basis for enhancing the analgesic efficacy of acupuncture through the modification of needles and promoting the development of acupuncture therapy. Please cite this article as: Sun MZ, Wang X, Li YC, Liu YH, Yu Y, Ren LJ, Gu W, Yao W. Effects of acupuncture needle modification on acupuncture analgesia. J Integr Med. 2025; 23(1): 66-78.
Needles ; Acupuncture Analgesia/methods* ; Animals ; Rats ; Male ; Acupuncture Points ; Rats, Sprague-Dawley

OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

Osteosarcoma (OS) is the most prevalent primary malignant bone tumor affecting children and adolescents. Despite ongoing research efforts, the 5-year survival rate has remained stagnant for many years, highlighting the critical need for novel drug development to enhance current treatment protocols. Ziyuglycoside II (ZYG II), a triterpenoid saponin extracted from S. officinalis, has recently demonstrated antitumor properties. This study evaluates the antitumor effect of ZYG II on osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma (ESRRG), which inhibits disease progression. The research employs in vitro experiments using multiple established osteosarcoma cell lines, as well as in vivo studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma. Additionally, ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYG II exerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53. Results indicate that ZYG II administration led to decreased OS cell viability and reduced tumor volumes. Furthermore, cell cycles were arrested at the G₀/G₁ phase, while the proportion of apoptotic cells increased. Expression of p53, ESRRG, p21, Bax, Cleaved Caspase-9, and Cleaved Caspase-3 proteins increased, while expression of CDK4, Cyclin D1, and Bcl-2 proteins decreased. Multiple ZYG II and ESRRG docking patterns were simulated through molecular docking. Comparing the pharmacodynamic response of ZYG II to OS cell lines with reduced ESRRG and normal expression demonstrated that ZYG II inhibits osteosarcoma progression, induces cell cycle arrest, and promotes cell apoptosis through the coordination of p53 and ESRRG. In conclusion, ZYG II inhibits osteosarcoma progression, leads to cell cycle arrest, and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.
Osteosarcoma/physiopathology* ; Tumor Suppressor Protein p53/genetics* ; Humans ; Animals ; Saponins/chemistry* ; Bone Neoplasms/physiopathology* ; Signal Transduction/drug effects* ; Cell Line, Tumor ; Mice, Nude ; Mice ; Apoptosis/drug effects* ; Receptors, Estrogen/genetics* ; Mice, Inbred BALB C ; Female ; Male ; Xenograft Model Antitumor Assays