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.

ObjectiveAngelicae Sinensis Radix， a commonly used medicinal herb with both medicinal and edible properties， is frequently adulterated in the market， severely affecting the clinical efficacy of preparations. While qualitative identification techniques for adulterants and counterfeits are now relatively mature， quantitative detection methods for adulterated processed products remain unexplored. Quantitative detection research of Angelicae Sinensis Radix and its primary closely related adulterant， "Tu Danggui" （Angelica gigas）， was conducted to establish a herbal quantitative molecular detection （Herb-Q） method for Angelicae Sinensis Radix and its processed products， providing a model for the establishment of quantitative detection technologies for Angelicae Sinensis Radix and related health products. MethodsThe specific single-nucleotide polymorphism （SNP） loci of Angelicae Sinensis Radix and Angelica gigas Nakai were screened based on the complete chloroplast genome sequence. The specific SNP loci of Angelicae Sinensis Radix were selected for quantitative methodological investigations （linearity， limit of quantification， limit of detection， and reproducibility） by mixing the powder of the herbs with different adulteration ratios. Huoxue Zhitong powder with three distinct adulteration ratios （15%， 25%， and 35%） was utilized to ascertain the precision of the Herb-Q method for the quantitative detection of Chinese patent medicines containing Angelicae Sinensis Radix. ResultsBy comparing the 123 chloroplast genome sequences of Angelicae Sinensis Radix， based on the principles of intraspecies conservation， interspecies specificity， and meeting the requirements of pyrophosphate high-throughput sequencing， it was determined that 9 674^th locus （A/G） in the chloroplast genome sequence NC_042826.1 and 38 592^nd locus （T/C） in the chloroplast genome sequence NC_029393.1 could be the exclusive molecular identification loci of Angelicae Sinensis Radix and Angelica gigas Nakai， respectively. The linear relationship R² of the Herb-Q method established by selecting the specific 9 674^th locus （A/G） of Angelicae Sinensis Radix was 0.997 4 （R²>0.99）， indicating an excellent linear relationship. The limits of quantification and detection were established at 2.0%， exhibiting excellent reproducibility ［relative standard deviation（RSD）<2.0%］. The established quantitative system based on the Herb-Q method detected the adulteration amount of counterfeit A. gigas in the Huoxue Zhitong powder， with an average deviation of 1.3% for three molecular quantitative replicates. ConclusionThis research demonstrates that the Herb-Q quantitative detection method established based on the 9 674^th locus （A/G） in the chloroplast genome sequence NC_042826.1 of Angelicae Sinensis Radix has good applicability， objectivity， and accuracy for Angelicae Sinensis Radix and A. gigas， and its processed products. This method has the capacity to provide technical support for the quantitative detection of commercially available Angelicae Sinensis Radix derivatives， including traditional Chinese medicinal preparations， dietary supplements， and nutraceuticals.

ObjectiveAngelicae Sinensis Radix， a commonly used medicinal herb with both medicinal and edible properties， is frequently adulterated in the market， severely affecting the clinical efficacy of preparations. While qualitative identification techniques for adulterants and counterfeits are now relatively mature， quantitative detection methods for adulterated processed products remain unexplored. Quantitative detection research of Angelicae Sinensis Radix and its primary closely related adulterant， "Tu Danggui" （Angelica gigas）， was conducted to establish a herbal quantitative molecular detection （Herb-Q） method for Angelicae Sinensis Radix and its processed products， providing a model for the establishment of quantitative detection technologies for Angelicae Sinensis Radix and related health products. MethodsThe specific single-nucleotide polymorphism （SNP） loci of Angelicae Sinensis Radix and Angelica gigas Nakai were screened based on the complete chloroplast genome sequence. The specific SNP loci of Angelicae Sinensis Radix were selected for quantitative methodological investigations （linearity， limit of quantification， limit of detection， and reproducibility） by mixing the powder of the herbs with different adulteration ratios. Huoxue Zhitong powder with three distinct adulteration ratios （15%， 25%， and 35%） was utilized to ascertain the precision of the Herb-Q method for the quantitative detection of Chinese patent medicines containing Angelicae Sinensis Radix. ResultsBy comparing the 123 chloroplast genome sequences of Angelicae Sinensis Radix， based on the principles of intraspecies conservation， interspecies specificity， and meeting the requirements of pyrophosphate high-throughput sequencing， it was determined that 9 674^th locus （A/G） in the chloroplast genome sequence NC_042826.1 and 38 592^nd locus （T/C） in the chloroplast genome sequence NC_029393.1 could be the exclusive molecular identification loci of Angelicae Sinensis Radix and Angelica gigas Nakai， respectively. The linear relationship R² of the Herb-Q method established by selecting the specific 9 674^th locus （A/G） of Angelicae Sinensis Radix was 0.997 4 （R²>0.99）， indicating an excellent linear relationship. The limits of quantification and detection were established at 2.0%， exhibiting excellent reproducibility ［relative standard deviation（RSD）<2.0%］. The established quantitative system based on the Herb-Q method detected the adulteration amount of counterfeit A. gigas in the Huoxue Zhitong powder， with an average deviation of 1.3% for three molecular quantitative replicates. ConclusionThis research demonstrates that the Herb-Q quantitative detection method established based on the 9 674^th locus （A/G） in the chloroplast genome sequence NC_042826.1 of Angelicae Sinensis Radix has good applicability， objectivity， and accuracy for Angelicae Sinensis Radix and A. gigas， and its processed products. This method has the capacity to provide technical support for the quantitative detection of commercially available Angelicae Sinensis Radix derivatives， including traditional Chinese medicinal preparations， dietary supplements， and nutraceuticals.

AIM:To investigate the effects of electroacupuncture at the Taiyang on refractive parameters and the expression of β-catenin and integrin β1 in the ciliary body of mice with form-deprivation myopia(FDM).METHODS:A total of 48 3-week-old healthy C57BL/6J mice were randomly divided into 4 groups: normal control(NC), FDM group, sham acupuncture(sham), and electroacupuncture at Taiyang acupoint(Taiyang), with 12 mice in each group. Mice in the FDM, sham, and Taiyang groups, wore translucent custom-made eye masks on the right eye to induce myopia. The Taiyang group received electroacupuncture stimulation at the Taiyang acupoint, while the sham group underwent non-penetrating stimulation with a blunt wooden stick. No intervention was performed on the NC group. Refraction and axial length were measured by infrared autorefractor and optical coherence tomography(OCT)before modeling and at 4 wk after modeling. The expression levels of β-catenin and integrin β1 in the ciliary body of mice at 4 wk after modeling were detected using quantitative real-time PCR(qPCR)and Western blotting(WB).RESULTS:After modeling for 4 wk, compared with the NC group, the FDM and sham groups showed significantly decreased refractive power(both P<0.05), elongated axial length(both P<0.05), and increased β-catenin and integrin β1 expression. Compared with the FDM and sham groups, the Taiyang group showed significantly increased refractive power(both P<0.05), shortened axial length(both P<0.05), and decreased β-catenin and integrin β1 expression.CONCLUSION:Electroacupuncture stimulation at the Taiyang acupoint effectively delayed the progression of myopia in FDM mice, and this effect may be partially mediated through modulating the expression of β-catenin and integrin β1 in the ciliary body.

Insulin-like growth factor-1(IGF-1)is a multifunctional growth factor which plays an important role in various physiological and pathological processes of the body by regulating biological behaviors such as cell proliferation, differentiation, and migration. Studies have found that abnormal expression of IGF-1 in the retina, sclera and other eye tissues can participate in the occurrence, development and prognosis of various ophthalmic diseases by regulating retinal autophagy flux and angiogenesis, adipogenic differentiation of orbital soft tissues and degradation of scleral extracellular matrix. This paper systematically integrates the expression level changes and mechanism of action of IGF-1 in ophthalmic diseases such as diabetic retinopathy(DR), age-related macular degeneration(ARMD), retinopathy of prematurity(ROP), Graves' ophthalmopathy, myopia, corneal injury and uveal melanoma(UM), and combines the latest clinical and animal experimental evidence to evaluate the bright prospects and potential risks of IGF-1 targeted therapy, in order to provide new ideas and theoretical basis for the prevention and treatment of ophthalmic diseases.

Objective:To identify the prognostic value of the Revised 15-item Myelodysplastic Syndrome-specific frailty scale (FS-15) in Chinese patients with myelodysplastic syndromes (MDS) .Methods:This retrospective study analyzed 812 patients with newly diagnosed MDS admitted to the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College from August 2016 to June 2023. Patients were assessed using the FS-15 and subsequently categorized into frail and non-frail groups. Clinical and laboratory characteristics, as well as overall survival (OS), were compared between these groups.Results:① The median patient age was 55 years ( IQR 45–64), with a median follow-up of 22.5 months (95% CI: 20.2–24.9) and a median OS of 43.3 months (95% CI: 36.8–49.8). The median FS-15 score was 0.42, with a cutoff value of 0.44. Male patients demonstrated higher median FS-15 scores than female patients (0.42 vs 0.38, P=0.006). In both the Revised International Prognostic Scoring System (IPSS-R; P=0.001) and Molecular International Prognostic Scoring System (IPSS-M; P=0.014) stratifications, FS-15 scores were significantly higher in the very high-risk group compared with the very low-risk group. ② The median OS was 54.7 months (95% CI: 47.5–NA) and 31.5 months (95% CI: 22.9–41.0) in the nonfrail ( n=452) and frail groups ( n=360), respectively ( P<0.001). The 3-year OS rates were (63.2 ± 3.2) % and (46.4 ± 3.6) % for the non-frail and frail groups, with 5-year OS rates of (49.9 ± 4.7) % and (32.0 ± 4.3) %, respectively ( P<0.001). ③Subgroup analysis revealed that nonfrail patients demonstrated significantly higher 3-year OS rates than frail patients in both the IPSS-M low-risk and very high-risk groups (all P<0.05). Similarly, nonfrail patients demonstrated superior 3-year OS rates compared with frail patients in the IPSS-R very low-risk, low-risk, and high-risk groups (all P<0.05). ④Among patients receiving hypomethylating agent therapy, the overall response rate was significantly higher in the non-frail group than in the frail group (86.7% vs 64.6%, P=0.007). Moreover, the frail group experienced higher rates of treatment-related adverse events, including febrile neutropenia (67.1% vs 47.4%, P=0.016) and liver function abnormalities (30.0% vs 14.5%, P=0.023), compared with the non-frail group. Conclusion:The FS-15 frailty score is a feasible and effective tool for assessing frailty in patients newly diagnosed with MDS in China and serves as a valuable prognostic indicator.

BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P＜0.05),and trabecular separation was elevated(P＜0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P＜0.05),and the level of osteocalcin was decreased(P＜0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P＜0.05);protein expression of β-Catenin and Frizzled9 was decreased(P＜0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P＜0.05)and a decrease in trabecular separation(P＜0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P＜0.05)and the serum level of osteocalcin was elevated(P＜0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P＜0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P＜0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P＜0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.

Objective To analyze the correlation between tongue image features and the risk levels of disease in patients with idiopathic membranous nephropathy(IMN).Methods Based on IMN clinical research electronic data acquisition system,a cross-sectional study method was used to analyze the clinical diagnosis and treatment data of 135 IMN patients from Guangdong Provincial Hospital of Chinese Medicine.The patients were grouped according to the risk levels of disease,and then the correlation between the risk levels of disease and tongue image features was analyzed.During the description of tongue image features,TB is for tongue body,TC is for tongue coating,L is for luminance,a is for red-green axis,G is for the value of green,B is for the value of blue,and AUT is for the value of autocorrelation.Results The comparison of tongue image feature indicators of patients with different risk levels of IMN showed that:(1)the higher the level of disease risk of IMN patients,the greater the values of TB-L,TB-G and TB-B(P<0.05 or P<0.01).The values of tongue image indicator TB-a and TC-a of the patients with different risk levels of IMN were shown in decreasing sequence:low-risk group>high-risk group>middle-risk group>extremely-high-risk group(P<0.05).(2)Linear regression analysis showed that TB-L,TB-G,and TB-B were significantly increased in the high-risk group compared with those in the middle-and low-risk groups(P<0.05 or P<0.01),whereas there were no significant differences between the middle-risk group and low-risk group(P>0.05).(3)The results of correlation analysis showed that there was a positive correlation among most of the tongue image feature indicators(including TB-L,TB-G,TB-B,TB-AUT,TC-L,TC-G,and TC-B,etc.)and the risk level of disease,while TB-a was negatively correlated with the risk level of disease,and the differences were all statistically significant(P<0.05 or P<0.01).(4)All patients were treated with Chinese medicine and/or Chinese patent medicine,and 46.7%of patients were given hormones and immunosuppressants,and there was no statistically significant difference in the the use of hormones and immunosuppressants among various groups(P=0.637).Conclusion There is a correlation between the tongue image features of IMN patients and the risk level of disease,and the results will provide an objective reference for the assessment of illness state and traditional Chinese medicine(TCM)syndrome differentiation of IMN patients.With reference to the changes in the tongue image features,the illness state can be precisely identified,which is more accurate than the inspection of four diagnostic methods of TCM.

Objective To investigate the forensic toxicological characteristics associated with etomidate abuse.Methods Blood and urine samples from six cases of etomidate abuse were quantitatively analyzed for etomidate and its metabolite etomidate acid.Relevant literature on etomidate abuse and poisoning was reviewed to summarize the pharmacological and toxicological effects of etomidate and case data.Results In the cases examined,the blood concentrations of etomidate and its metabolite,etomidate acid,were relatively low,ranging from 1.97～187.61 ng/mL and 12.29～316.31 ng/mL,respectively.Urine samples offered a broader detection window,with etomidate concentrations ranging from 1.65 to 700.89 ng/mL and etomidate acid concentrations from 295.26～214 483.52 ng/mL.Notably,in a sexual assault case,the victims's blood concentration of etomidate acid dropped below 6.98 ng/mL eight hours post-ingestion,while urinary concentration was still above 59 449.02 ng/mL.Conclusion Abuse of electronic cigarettes containing etomidate can result in severe overdoses.Given that etomidate is rapidly metabolized in vivo,it is essential to collect and analyze biological samples promptly,with a particular emphasis on detecting its metabolite,etomidate acid.

Purpose To investigate the evaluation value of multimodal MRI in the outcome of traumatic brain injury(TBI)in rats.Materials and Methods A total of 30 TBI rat models were established,randomly divided into an untreated TBI group and a TBI treated group(hyperbaric oxygen)with 15 rats each.The Sham group with 15 rats was used as a healthy control,and the brain injury status of the rats was evaluated at 1 d,3 d,7 d,14 d and 28 d of modeling.Multimodal MRI was performed in parallel,and coronary T2WI,diffusion weighted imaging,diffusion kurtosis imaging and diffusion tensor imaging sequences were routinely scanned.The correlation between rat neurological function scores and various sequence parameters were analyzed,as well as multimodal MRI and the outcome of brain injury after TBI treatment in rats.Results The neurological function score and average kurtosis of the TBI treatment group were lower than those of the TBI untreated group(P<0.05).The apparent diffusion coefficient and anisotropy score of the TBI treatment group were higher than those of the TBI untreated group(P<0.05).The diffusion weighted imaging parameter apparent diffusion coefficient value and diffusion tensor imaging parameter fraction anisotropy value were negatively correlated with the degree of brain injury in TBI rats after 28 days of treatment(r=-0.675,-0.611,P<0.05),while the diffusion kurtosis imaging parameter mean kurtosis value was positively correlated with the degree of brain injury in TBI rats after 28 days of treatment(r=0.623,P<0.05).Conclusion Multimodal MRI can effectively evaluate the brain injury status of TBI rats and provide valuable information for dynamic evaluation after hyperbaric oxygen therapy for TBI,with high evaluation value in treatment outcomes.