ObjectiveTo establish the specific chromatogram of Chuanxiong Rhizoma dispensing granules（CRdg）， and to evaluate its quality by chemometrics and two reference substances for determination of multiple components（TRSDMC）. MethodsHigh performance liquid chromatography（HPLC） specific chromatograms were established using 13 batches of CRdg from 7 manufacturers， and preliminary quality evaluation was performed by similarity evaluation and chemometrics analysis. Eight characteristic peaks in the specific chromatogram of CRdg were measured on 22 different types of C₁₈ columns， and the actual retention times were recorded. Taking chlorogenic acid（peak 1） and senkyunolide A（peak 8） as double standard compounds， the retention times of the eight characteristic peaks were predicted by linear calibration using two reference substances（LCTRS）， and the method was validated on three other columns of different brands. Taking chlorogenic acid as reference peak， the relative correction factor method（RCFM） was used to quantify cryptochlorogenic acid， caffeic acid， ferulic acid， senkyunolide I and senkyunolide A， and the results were compared with the external standard method（ESM）. ResultsThe similarities of specific chromatograms of 13 batches of CRdg were all >0.90， and a total of 8 characteristic peaks were calibrated， and six of them were identified， including chlorogenic acid（peak 1）， cryptochlorogenic acid（peak 2）， caffeic acid（peak 3）， ferulic acid（peak 5）， senkyunolide I（peak 6） and senkyunolide A（peak 8）. Through chemometric analysis， it was found that ferulic acid， chlorogenic acid， senkyunolide I and cryptochlorogenic acid were the main components causing quality difference in CRdg， and the accuracy of LCTRS in predicting the retention time of 8 characteristic peaks was superior to that of the relative retention time method（RRT）. Further comparison of the results obtained from RCFM and ESM showed that there was no statistically significant difference between the two methods. ConclusionA quality evaluation method for CRdg based on HPLC specific chromatogram and TRSDMC is established， its qualitative accuracy is better than that of RRT， the quantitative accuracy is similar to that of ESM， and 4 quality-differentiated components among different manufacturers are found. This method is stable and reliable， and has reference value for the quality evaluation of other dispensing granules.

ObjectiveTo establish the specific chromatogram of Chuanxiong Rhizoma dispensing granules（CRdg）， and to evaluate its quality by chemometrics and two reference substances for determination of multiple components（TRSDMC）. MethodsHigh performance liquid chromatography（HPLC） specific chromatograms were established using 13 batches of CRdg from 7 manufacturers， and preliminary quality evaluation was performed by similarity evaluation and chemometrics analysis. Eight characteristic peaks in the specific chromatogram of CRdg were measured on 22 different types of C₁₈ columns， and the actual retention times were recorded. Taking chlorogenic acid（peak 1） and senkyunolide A（peak 8） as double standard compounds， the retention times of the eight characteristic peaks were predicted by linear calibration using two reference substances（LCTRS）， and the method was validated on three other columns of different brands. Taking chlorogenic acid as reference peak， the relative correction factor method（RCFM） was used to quantify cryptochlorogenic acid， caffeic acid， ferulic acid， senkyunolide I and senkyunolide A， and the results were compared with the external standard method（ESM）. ResultsThe similarities of specific chromatograms of 13 batches of CRdg were all >0.90， and a total of 8 characteristic peaks were calibrated， and six of them were identified， including chlorogenic acid（peak 1）， cryptochlorogenic acid（peak 2）， caffeic acid（peak 3）， ferulic acid（peak 5）， senkyunolide I（peak 6） and senkyunolide A（peak 8）. Through chemometric analysis， it was found that ferulic acid， chlorogenic acid， senkyunolide I and cryptochlorogenic acid were the main components causing quality difference in CRdg， and the accuracy of LCTRS in predicting the retention time of 8 characteristic peaks was superior to that of the relative retention time method（RRT）. Further comparison of the results obtained from RCFM and ESM showed that there was no statistically significant difference between the two methods. ConclusionA quality evaluation method for CRdg based on HPLC specific chromatogram and TRSDMC is established， its qualitative accuracy is better than that of RRT， the quantitative accuracy is similar to that of ESM， and 4 quality-differentiated components among different manufacturers are found. This method is stable and reliable， and has reference value for the quality evaluation of other dispensing granules.

ObjectiveTo establish the quality standards for Sennae Folium（Cassia angustifolia） dispensing granules based on standard decoctions. MethodsHigh performance liquid chromatography（HPLC） specific chromatograms were established for 15 batches of Sennae Folium（C. angustifolia） standard decoctions and 10 of Sennae Folium（C. angustifolia） dispensing granules from different manufacturers， and the similarity evaluation， hierarchical cluster analysis（HCA） and principal component analysis（PCA） were performed. Linear calibration with two reference substances（LCTRS） and quantitative analysis of multi-components by single-marker（QAMS） were established for the common peaks in the specific chromatograms to determine the contents of main components in the decoction pieces， standard decoctions and dispensing granules， and to calculate their transfer rates from decoction pieces to standard decoctions and dispensing granules. ResultsThe similarities of specific chromatograms of 15 batches of Sennae Folium（C. angustifolia） standard decoctions and 10 batches of Sennae Folium（C. angustifolia） dispensing granules were all greater than 0.95， and a total of 8 characteristic peaks were calibrated， and five of them were identified， including kaempferol-3，7-O-diglucoside， apigenin-6，8-di-C-glucoside， quercetin-3-O-gentianoside， sennoside B and sennoside A. HCA and PCA results showed that there were certain differences in the composition of different batches of standard decoctions， but no clustering was observed in the production area. As the standard decoctions， the extract rate of 15 batches of samples was 26.54%-45.38%， the contents of kaempferol-3，7-O-diglucoside， apigenin-6，8-di-C-glucoside， quercetin-3-O-gentianoside， sennoside B and sennoside A were 12.16-19.26， 2.57-4.94， 3.27-5.11， 6.75-11.39， 4.69-7.79 mg·g^-1， and their transfer rates from decoction pieces to standard decoctions were 45.41%-79.02%， 29.12%-55.07%， 40.52%-67.90%， 24.72%-49.12%， 27.54%-49.34%， respectively. The extract rates of Sennae Folium（C. angustifolia） dispensing granules（C8-C10） were 38.10%-39.50%， the transfer rates of the above five components from decoction pieces to dispensing granules were 72.85%-73.58%， 53.43%-53.94%， 40.19%-40.74%， 24.62%-25.00%， 28.65%-29.11%， respectively， which were generally consistent with the transfer rates from decoction pieces to standard decoctions. ConclusionCompared with the relative retention time method， LCTRS has higher prediction accuracy and is more suitable for chromatographic columns. The established quality control standard of Sennae Folium（C. angustifolia） dispensing granules based on standard decoction is reasonable and reliable， and all indicators of samples from different manufacturers are within the range specified based on the standard decoction， which can provide reference for the quality control and process research of this dispensing granules.

Objective To compare the effects of proprioceptive neuromuscular facilitation(PNF),con-centric-isometric-eccentric fast training(CIEFT),and concentric-isometric-eccentric slow training(CI-EST)in young adults with flexible flatfoot.Methods Forty participants were randomly allocated into a PNF group,a CIEFT group,a CIEST group and a control group,each of 10.The PNF,CIEFT and CIEST groups underwent six weeks of training as their group names indicated.Then the height differ-ence in the navicular drop test(NDt),normalized navicular height truncated(NNHt),muscle strength of ankle joint,plantar pressure distribution characteristics,and dynamic balance of all groups were re-corded before and after the intervention.Results As to the arch morphology,compared with pre-inter-vention,NDt decreased significantly in the dominant side of PNF group(P=0.049)and the non-domi-nant side of CIEFT group(P=0.034),while NNHt increased significantly in the non-dominant side of CIEFT group(P=0.026).Moreover,compared with pre-intervention,the muscle strength of plantar flex-ion increased significantly in all groups except the control group(dominant/non-dominant side:P=0.003/P=0.004,P=0.000/P=0.000,P=0.001/P=0.001),and that of inversion increased significantly in both PNF and CIEFT groups(dominant/non-dominant side:P=0.011/P=0.005,P=0.003/P=0.003).When it comes to the plantar pressure distribution characteristics,after the intervention,in the non-dominant side,the incremental center of pressure(COP)connections decreased significantly in CIEFT group(P=0.037),while the ratio of medial arch load and the contact area of the medial arch in PNF group de-creased significantly(P=0.012,P=0.027).Moreover,in the dominant side,the contact area decreased significantly in CIEST group(P=0.038),but increased significantly in the control group(P=0.015).What's more,after intervention,the Y-balance test score increased significantly in both sides of PNF and CIEST groups and the dominant side of CIEFT group(P=0.006/P=0.023,P=0.001/P=0.035,P=0.011).Conclusion Through a 6-week exercise intervention,PNF can improve the foot arch morphology and enhance dynamic balance ability in young adults with flexible flatfoot,while concentric-isometric-eccen-tric fast and slow training is superior in improving the foot arch morphology and the dynamic balance ability,respectively.

Objective To investigate the therapeutic efficacy of combining fractional CO2 laser with triam-cinolone acetonide and econazole nitrate cream for the treatment of vulvar lichen sclerosus(VLS).Methods The clinical data of 113 patients with vulvar lichen sclerosus(VLS)were retrospectively analyzed.The patients were divided into an observation group and a control group based on different treatments received.Clinical symptoms(vulvar itching,painful intercourse)and signs(vulvar skin color,vulvar skin elasticity,range of vulvar lesions)were scored using the Cattaneo scoring criteria.The Cattaneo scores before and after treatment were recorded for each patient,and comparisons were made between groups in terms of Cattaneo scores and occurrence of adverse reac-tions.The therapeutic efficacy of fractional CO2 laser combined with triamcinolone acetonide and econazole nitrate cream was evaluated.Results After three treatments,both groups exhibited a significant decrease in Cattaneo scores,with a statistically significant difference(P<0.05).The study group demonstrated a significantly greater reduction in Cattaneo scores compared to the control group(P<0.05).Furthermore,the cure rate of VSL was higher in the study group than in the control group(25.86%vs.10.91%,P<0.05).Regarding adverse effects,there was no statistically significant difference between the two groups(P>0.05).Conclusions Compared to the single application of fractional CO2 laser,the combination of fractional CO2 laser with triamcinolone acetonide and econazole nitrate cream demonstrates enhanced efficacy in alleviating signs and symptoms among patients with vulvar sclerosing tundra,while minimizing adverse reactions.This approach holds significant potential for clinical implementation.

BACKGROUND:Lower limb peri-knee muscle strength training and neuromuscular electrical stimulation are generally safe and effective rehabilitation methods for patellofemoral joint pain,but the mechanism of their intervention is still unclear. OBJECTIVE:To determine the effect of muscle strength training combined with neuromuscular electrical stimulation on pain,lower extremity function and biomechanical characteristics in patients with patellofemoral pain. METHODS:Thirty-seven patients with patellofemoral pain were randomly divided into muscle strength training combined with electrical stimulation group(trial group,n=19)and muscle strength training group(control group,n=18).Both groups underwent intervention training for 6 weeks,three times a week.The visual analog scale and anterior knee pain scale were used to evaluate the pain level and functional level of the knee.Kinematic and kinetics data during running were collected by using an infrared motion capture system and a three-dimensional force platform simultaneously.A two-way analysis of variance with repeated measures(group*time)was applied to analyze the data. RESULTS AND CONCLUSION:(1)After the intervention,the visual analog scale scores of the trial group and the control group were significantly decreased(P<0.001),and the anterior knee pain scale scores were significantly increased(Ptrial group<0.001,Pcontrol group=0.001)in the trial group and control group.The anterior knee pain scale scores of the trial group were significantly higher compared to the control group after the intervention(P=0.001).(2)The peak knee flexion angle(P=0.011),peak knee extension moment(P<0.001),the peak knee internal rotation moment(P=0.008),the peak patellofemoral stress(P<0.001)and the peak patellofemoral contact force(P<0.001)were significantly decreased in the trial and control groups during running after the intervention compared with those before the intervention.(3)In conclusion,both muscle strength training and muscle strength training combined with electrical stimulation training are helpful to improve the subjective pain and lower limb function of patellofemoral pain patients,enhance the movement pattern during running and reduce the stress of the patellofemoral joint.Compared with muscle strength training alone,muscle strength training combined with electrical stimulation can improve lower limb function more significantly.

AIM To explore the clinical effects of Bushen Huoxue Ointment Formula on patients with ankylosing spondylitis of Kidney Deficiency and Blood Stasis Pattern.METHODS One hundred and sixty-seven patients were randomly assigned into control group(55 cases)for 2-year intervention of conventional treatment,exposure group(54 cases)for 2-year intervention of both Bushen Huoxue Decoction and conventional treatment,and high exposure group(58 cases)for 2-year intervention of Bushen Huoxue Ointment Formula,Bushen Huoxue Decoction and conventional treatment.The changes in clinical effects,BASDAI score,ASDAS-CRP,BASFI score,spinal pain score,PGA score,BASMI score,ASQoL score,SPARCC score,Kidney Deficiency and Blood Stasis Pattern score,ESR,CRP,IL-6,TNF-α,IL-17,IL-23,IL-35,NLR,PLR and safety indices were detected.RESULTS The high exposure group demonstrated more ASAS40,ASASAS5/6,BASDAI50 cases than the exposure group and the control group(P<0.05).After the treatment,the high exposure group displayed lower BASDAI score,ASDAS-CRP,BASFI score,spinal pain score,PGA score,BASMI score,SPARCC score,ASQoL score,Kidney Deficiency and Blood Stasis Pattern score,ESR,CRP,IL-6,TNF-α,IL-17,IL-23 than the other two groups(P<0.05),and higher IL-35(P<0.05).After adjusting confounding factors by logistic regression analysis,Bushen Huoxue Decoction and Bushen Huoxue Ointment Formula reduced BASDAI score,ASDAS-CRP(P<0.05),and enhanced clinical effects(P<0.05).No serious adverse reactions were found in the three groups.CONCLUSION For the patients with ankylosing spondylitis of Kidney Deficiency and Blood Stasis Pattern,Bushen Huoxue Ointment Formula can safely and effectively inhibit inflammation,reduce disease activity,alleviate bone marrow edema,improve clinical symptoms,and enhance joint functions and life quality.

OBJECTIVE To confirm the therapeutic effect of Jintiange capsules on osteoarthritis(OA) and the potential mechanism of synovial mesenchymal stem cell exosomes(SMSC-Exos) and articular chondrocytes(ACs) in the treatment of OA based on high-throughput sequencing technology. METHODS Type Ⅱ collagenase-induced OA rats were used for efficacy verification through general behavioral observation, bipedal balance difference experiment, mechanical foot reflex threshold, Micro-CT observation, and Safranin O-Fast Green staining. SMSCs and ACs were cultured in suitable concentration of drug-containing serum, and mRNA sequencing was performed on ACs in the control, model, and Jintiange capsules groups, as well as miRNA sequencing on SMSC-Exos. Differential expressed mRNAs and miRNAs were screened and target genes were predicted. The common differential expressed genes between SMSC and ACs were obtained by intersecting the differential expressed genes, and a miRNA-mRNA regulatory network was constructed using Cytoscape software. The expression trend analysis of common differential expressed genes was conducted, as well as the correlation analysis between differential expressed gene mRNA and miRNA, Micro-CT efficacy indicators, and differential expressed gene mRNA. RESULTS Under the pathological state of OA, the expression of miRNA-23a-3p, miRNA-342-3p, miRNA-146b-5p, miRNA-501-3p, and miRNA-214-3p were down-regulated, while miRNA-222-3p, miRNA-30e-3p, miRNA-676-3p, and miRNA-192-5p were up-regulated (P<0.05). The expressions of these miRNAs were significantly reversed after intervention with drug-containing serum of Jintiange capsules. There was a certain correlation between Micro-CT efficacy indicators, mRNA and miRNA. CONCLUSION Jintiange capsule has obvious efficacy in the treatment of OA, and its mechanism may be related to the promotion of SMSC-Exos targeting ACs to transport miRNA and then regulate Serpinb10, Ntn1, Il1b, Tgm2, Megf10, Il11, Cd40, Slc15a3, Pou2f2 and other genes.

ObjectiveTo investigate the effect of different doses of Jiedu Tongluo Shengjin prescription （JTSP） on serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and forkhead box P3 （FoxP3） in submandibular gland of NOD/Ltj mice with Sjögren's syndrome， and to explore the mechanism of JTSP on immune regulation in NOD/Ltj mice. MethodThirty NOD/Ltj mice （eight weeks old） were randomly divided into model group， JTSP low-dose group， JTSP medium-dose group， JTSP high-dose group and hydroxychloroquine group， and were administrated with normal saline， JTSP 9， 18， and 36 g·kg^-1， and hydroxychloroquine 60 mg·kg^-1 daily， respectively from the age of 12 weeks. Six ICR mice were given an equal amount of normal saline by gavage as the control group. During the experiment， daily water consumption and saliva secretion of mice at the age of 9， 12， 16 weeks were recorded. After 4 weeks of administration， submandibular gland and spleen tissues were dissected to calculate corresponding indexes. The pathological morphology of submandibular gland was observed by hematoxylin-eosin （HE） staining. Meso Scale Discovery （MSD） and immunohistochemistry were employed to detect the serum levels of IL-6， TNF-α and IL-10， and the expression and distribution of FoxP3 in submandibular gland， respectively. The protein expression of FoxP3 in mouse submandibular gland was determined by Western blot， and the mRNA expressions of FoxP3 and TNF-α were determined by real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the control group， the model group presented increased daily water consumption， decreased saliva secretion， lowered submandibular gland index， elevated pathological score of submandibular gland， up-regulated serum IL-6 and TNF-α and mRNA expression of TNF-α while down-regulated serum IL-10 and protein and mRNA expressions of FoxP3 in submandibular gland （P<0.05）. Compared with the conditions in model group， daily water consumption in JTSP groups was reduced while saliva secretion was increased， especially in medium-dose and high-dose groups （P<0.05）， and there was an increase in the submandibular gland index of JTSP medium-dose group （P<0.05） while a decrease in the spleen index of JTSP high-dose group （P<0.05）. Additionally， JTSP groups had lower pathological score of submandibular gland than the model group （P<0.05）， especially high-dose group， as well as lower serum IL-6 and TNF-α and mRNA expression of TNF-α while higher serum IL-10 （P<0.05）. JTSP at medium and high doses up-regulated the protein and mRNA expressions of FoxP3 in submandibular gland （P<0.05）. ConclusionJTSP may inhibit the secretion of inflammatory cytokines by regulating the stability of FoxP3⁺ regulatory T （Treg） cells， thus alleviating the systemic immune inflammation in Sjögren's syndrome.

Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.
Animals ; Humans ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Heterografts ; Photothermal Therapy ; Biomimetics ; Disease Models, Animal ; Head and Neck Neoplasms/therapy* ; Cell Line, Tumor ; Tumor Microenvironment