BACKGROUND:Troxerutin has been found to have a significant ameliorative effect on brain disorders,but there are fewer studies on the effects of troxerutin on the treatment of cerebral infarction and on neuronal cells. OBJECTIVE:To investigate the mechanism by which troxerutin regulates nuclear factor-κB signaling pathway to reduce brain injury and neuronal apoptosis in cerebral infarction rats. METHODS:Fifty clean grade rats were randomized into healthy group,model group,and troxerutin+nuclear factor-κB agonist group,troxerutin group,and nuclear factor-κB inhibitor group.Except for the healthy group,all other groups were used to establish a rat model of cerebral infarction by arterial ligation.The healthy and model groups were treated once a day with an equal amount of physiological saline by gavage.The troxerutin+nuclear factor-κB agonist group was intervened with 72 mg/kg troxerutin by gavage+20 mg/kg RANK intraperitoneally.The troxerutin group was treated with 72 mg/kg troxerutin by gavage.The nuclear factor κB inhibitor group was intervened intraperitoneally with 120 mg/kg nuclear factor κB inhibitor pyrrolidine disulfiram.Administration in each group was given once a day for 30 continuous days.Zea-longa was used to detect neurological damage in rats,hematoxylin-eosin staining was used to observe pathological changes,TUNEL was used to detect neuronal apoptosis,and immunoblotting and PCR were used to detect the expression of nuclear factor-κB p65 and nuclear factor-κB p50 at protein and mRNA levels,respectively. RESULTS AND CONCLUSION:Compared with the healthy group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65,nuclear factor-κB p50 mRNA and protein expression levels were elevated in the model group(P＜0.05).Compared with the model group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were decreased in the troxerutin+nuclear factor-κB agonist group(P＜0.05).Compared with the troxerutin+nuclear factor-κB agonist group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were reduced in the troxerutin group and nuclear factor-κB inhibitor group(P＜0.05).In addition,there was no difference between the troxerutin group and the nuclear factor-κB inhibitor group(P＞0.05).In the model group,there was a large number of cytoplasmic vacuolation,obvious edema and necrosis,and a large number of inflammatory cell infiltrations.In the troxerutin+nuclear factor-κB agonist,the swelling of brain tissue was reduced,and reticulate structures and condensed cells were reduced,still with some edema.In the troxerutin group and nuclear factor-κB inhibitor group,brain tissue swelling,neuronal edema degeneration,cytoplasmic vacuolation and neuronal nucleus consolidation were reduced,and the inflammatory cell infiltration was significantly decreased.To conclude,troxrutin can reduce the expression of neurological impairment,inhibit neuronal apoptosis and improve the pathological injury of brain tissue in rats with cerebral infarction,and its mechanism of action may be related to the modulation of nuclear factor-κB expression and related signaling pathways.

Objective:To investigate the response of mandibular condylar chondroprogenitors to flow fluid shear stress(FFSS).Methods:Chondroprogenitors were in vitro cultured and stimulated with FFSS that can cause cell degeneration,and treated with sec-ond-generation high-throughput RNA sequencing.Differential gene expression was screened using DESeq2 software for gene ontology(GO)functional enrichment analysis,kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis and protein-protein interaction(PPI)network analysis.qRT-PCR was performed to validate the core genes screened by PPI.Results:A total of 1996 differentially expressed genes were obtained,mainly including inflammatory response and cell cycle related molecules.Among them,Actal,Atf3,Ccl2,116,Nfkbia,Ret and Vcaml were identified as the core genes.Conclusion:FFSS stimulation affects chondroprogenitor function by acting on inflammatory responses and cell cycle-related signaling pathways in chondroprogenitors.

Objective:To investigate the effects of the taurochenodeoxycholic acid(TCDCA)on cartilage degeneration in tem-poromandibular joint osteoarthritis(TMJ OA).Methods:36 female SD rats aged 6 weeks were randomly divided into 3 groups:con-trol group(CON),unilateral anterior crossbite group(UAC),UAC plus TCDCA injection group(UAC+TCDCA).UAC model was es-tablished in all rats in UAC and UAC+TCDCA groups.Samples were collected at 8 and 12 weeks(control group,UAC group,UAC+TCDCA group)after set up of the experiment(n=6),and TMJ morphological examination was performed.The expression of CYP7A1,BAAT and TGR5 in the tissue and cells was examined by immunohistochimical staining.Results:(1)Compared with the CON group of the same age,the cells in the condylar cartilage were disordered,the cartilage matrix was reduced and thinner in UAC group.Compared with UAC group of the same age,cell arrangement,cell number,cartilage matrix and cartilage thickness were im-proved in UAC+TCDCA group(P＜0.05).(2)Compared with the CON group of the same age,the positive cells for TCDCA-specific receptor TGR5 and the key enzymes CYP7A1 and BAAT were mainly distributed in the anterior hypertrophic layer and hypertrophic layer at each time point.The number of positive cells in the UAC group was significantly reduced compared with the CON group.Conclusion:TCDCA has obvious therapeutic effects on the degeneration in TMJ OA.

Objective:To explore the predictive value of uterine artery blood flow parameters of Doppler ultrasound combined with coagulation related indicators on the pregnancy outcome of recurrent abortion caused by thrombophilia.Methods:A total of 82 patients with recurrent abortion who admitted to the department of gynecology outpatient of Beijing Haidian Hospital from January 2020 to January 2023 were selected.All patients received relevant treatment,and the follow-up results were calculated as statistic method.Before treatment on the day after admission,uterine artery pulse index(PI),resistance index(RI),the ratio of the maximum blood flow velocity of systolic pressure(S)to the maximum blood flow velocity of end-diastolic(D)(S/D),and activated partial thromboplastin time(APTT),prothrombin time(PT),fibrinogen(FIB),thrombin time(TT)and D-dimer(D-D)of all patients were detected.Pearson correlation analysis was adopted to analyze the correlations between PI,RI,S/D and each of APTT,PT,FIB,TT and D-D.Receiver operating characteristic(ROC)curve was used to analyze the values of single PI,RI,S/D,APTT,PT,FIB,TT and D-D,and the value of the combined detection of them in predicting the pregnancy outcome of recurrent abortion caused by thrombophilia.Results:Follow up results showed that 49 cases of 82 patients with recurrent abortion were successful pregnancy and 33 cases of them occurred pregnancy loss,and the PI,RI and S/D of pregnant women with successful pregnancy were significantly lower than those of pregnant women who occurred pregnancy loss,with statistical significance(t=10.598,6.693,3.059,P<0.05).The levels of APTT,PT,FIB,TT and D-D of pregnant women with successful pregnancy were significantly lower than those of pregnant women who occurred pregnancy loss,and the differences were statistically significant(t=9.552,96.462,22.767,5.100,95.805,P<0.05),respectively.PI appeared respectively positive correlation with APTT,PT,FIB,TT and D-D(r=3.178,P<0.05),and RI appeared respectively positive correlation with APTT,PT,FIB and D-D(r=3.246,P<0.05),and S/D also appeared respectively positive correlation with PT,FIB,TT and D-D(r=3.246,P<0.05).The sensitivities of single PI,RI,S/D,APTT,PT,FIB,TT and D-D detection,and the combined detection of them were respectively 42.40%,48.50%,39.40%,48.50%,63.60%,72.70%,42.40%,39.40%and 84.80%in predicting the pregnancy outcome of recurrent abortion caused by thrombophilia.The specificities of them were respectively 98.00%,71.40%,55.10%,75.50%,59.20%,71.40%,77.60%,85.70%and 98.80%,and the AUC values of them were respectively 0.674,0.685,0.409,0.646,0.784,0.788,0.566,0.563 and 0.941.Conclusion:Both single and combination of PI,RI and S/D of uterine artery blood flow parameters,as well as APTT,PT,FIB,TT and D-D of coagulation related indicators,have a certain value in predicting pregnancy outcome of recurrent abortion caused by thrombophilia,and the combined detection has higher predictive value.

Objective To investigate the progress of two-dimensional echocardiographic parameters in patients with different severity of aortic stenosis.Methods A retrospective analysis was per-formed on 96 patients diagnosed with aortic stenosis with at least 2 times of transthoracic echo-cardiography(interval ≥1 year)in Department of Cardiology,Fourth Medical Center of Chinese PLA General Hospital from March 2017 to December 2023.According to aortic stenosis severity,they were divided into a mild group(72 cases),a moderate group(14 cases)and a severe group(10 cases).Peak pressure gradient(PPG)across aortic valve,Vmax,mean aortic valve pressure gradient(ΔPm),pulmonary artery systolic pressure(PASP)were collected,and the changes and annual progress of these echocardiographic parameters at baseline and before and after follow-up were analyzed.Results The values of IVST,LVPWT,Vmax,aortic valve PPG and ΔPm were sig-nificantly increased in the mild,moderate and severe stenosis groups in turn(P＜0.05,P＜0.01).The values of Vmax,PPG and ΔPm were significantly lower in the mild stenosis group than the moderate and severe stenosis groups,and the LVPWT value was obviously lower in the mild ste-nosis group than the severe stenosis group(P＜0.05).The aortic valve PPG and ΔPm values at follow-up were significantly higher than those before the follow-up in the three stenosis groups(P＜0.05,P＜0.01).After follow-up,the Vmax values in mild and moderate stenosis groups were notably higher than before(P＜0.01).The PASP value at follow-up was significantly higher than before in the severe stenosis group(P＜0.05).The annual progression rate of Vmax,PASP,LVEF were gradually increased in the mild,moderate,and severe stenosis groups(P＞0.05).The annual progression rate of ΔPm was gradually increased in the three groups in turn(2.30±1.77 mm Hg/year vs 2.40±1.18 mm Hg/year vs 6.08±1.70 mm Hg/year,P＜0.05).Conclusion As the severity of baseline aortic stenosis increases,obvious changes are observed in cardiac structure and function.Before and after follow-up,the serious the aortic stenosis severity is,the faster the annual progression rates of Vmax,PPG,LVEF and PASP are.

ObjectiveA rapid method for identification of chemical constituents in Puerariae Lobatae Radix dispensing granules was established in order to clarify the material basis. MethodThe chemical constituents of Puerariae Lobatae Radix dispensing granules was qualitatively analyzed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） under positive and negative ion modes， and the chromatographic conditions were on an ACQUITY UPLC HSS T3 column（2.1 mm×100 mm， 1.8 μm） with 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） as mobile phase for gradient elution（0-4 min， 5%-10%B； 4-10 min， 10%-15%B； 10-20 min， 15%-16%B； 20-27 min， 16%-31%B； 27-33 min， 31%-59%B； 33-42 min， 59%-95%B； 42-42.1 min， 95%-5%B； 42.1-45 min， 5%B）， the flow rate was 0.35 mL·min^-1， the column temperature was 40 ℃， the injection volume was 5 μL， and electrospray ionization（ESI） was selected. Then these chemical constituents were comprehensively identified based on PeakView 1.2， PubChem， ChemicalBook， ChemSpider， comparative control profiles and literature information. ResultA total of 128 chemical constituents were identified from the dispensing granules， including 60 flavonoids， 26 organic acids， 7 glycosides， 6 coumarins， 3 nucleosides and 26 other compounds. By focusing on the cleavage patterns of flavonoids， organic acids， glycosides， coumarins， nucleosides and other compounds， 12 compounds that have not been reported in Puerariae Lobatae Radix species were identified from the dispensing granules. ConclusionThe established method can systematically and rapidly identify the chemical constituents in Puerariae Lobatae Radix dispensing granules， and cleared it composition is mainly flavonoids and organic acids. Laying a foundation for the study of the material basis， mechanism of action and clinical application of the dispensing granules.

Objective:To investigate the effects of needle-embedding therapy on improvement of pneumoperitoneum and abdominal distension after colonoscopy.Methods:A total of 102 patients who received colonoscopy in Hangzhou Hospital of Traditional Chinese Medicine, China between June 2018 and June 2020 were included in this study. They were randomly assigned to observation and control groups ( n = 51 per group). The control group was subjected to routine symptomatic treatment and the observation group was given needle-embedding therapy. The improvement effects on pneumoperitoneum and abdominal distension, examination duration, numerical rating scale score, and grade of abdominal distension at 6 and 24 hours after colonoscopy were compared between observation and control groups. Results:Total response rate in the observation group was significantly higher than that in the control group [92.16% (47/51) vs. 74.51% (38 /51), χ 2 = 5.71, P < 0.05]. The time to enteroscope entry and the time to enteroscope withdrawal were (4.86 ± 1.23) minutes and (5.24 ± 1.13) minutes, respectively, which were significantly shorter than those in the control group [(8.79 ± 1.25) minutes, (6.97 ± 1.12) minutes, t = 16.00, 7.76, both P < 0.001]. Numerical rating scale score in the observation group was significantly lower than that in the control group [(1.50 ± 0.41) points vs. (2.30 ± 0.42) points, t = 9.73, P < 0.001). At 6 and 24 hours after colonoscopy, the amplitude of improvement of abdominal distension in the observation group was significantly greater than that in the control group (both P < 0.05). Conclusion:Needle-embedding therapy can effectively improve pneumoperitoneum and abdominal distension after enteroscopy, shorten the examination duration, and relieve pain.

Objective:To describe and analyze the clinical manifestations of patients with orofacial pain of temporomandibular disorders (TMD).Methods:A retrospective study on orofacial pain was conducted for 3 425 patients diagnosed as TMD based on clinical symptoms and signs in the Department of Temporomandibular Disorders and Orofacial Pain, School of Stomatology, The Fourth Military Medical University. The patients included 1 158 males and 2 267 females with a median age of 32 years. The gender, age, course of disorders, pattern and site of pain, CT imaging diagnosis of temporomandibular joint (TMJ) were analyzed. The distribution of gender, age and disorder course interval were described. The differences in frequency of the pattern and site of pain, imaging diagnosis in different gender, age and disease course interval were compared. Chi-square test and non-parametric rank sum test were performed using software SPSS 23.0.Results:Of the 3 425 patients, 29.1% (997/3 245) had signs of joint popping, and 40.1% (1 373/3 425) had restricted opening. The pain frequency was higher in males who had disorder course less than 1 month ( P<0.01) and also in males who had open-and-close and/or lateral excursion and/or protrusion pain without tenderness or other pain without tenderness ( P<0.05). However, the pain frequency was higher in females who had tenderness ( P<0.01). The pain frequencies in those over 56 years old with tenderness combined with open-and-close and/or lateral excursion and/or protrusion pain were higher than in patients of other ages ( P<0.01). In patients with unilateral TMJ pain, the frequency in males was higher than females( P<0.01), while the frequency in females was higher in patients with unilateral TMJ pain combined with unilateral or bilateral myalgia and the frequency was higher in patients under 15 years old having bilateral TMJ pain and/or unilateral or bilateral myalgia ( P<0.05). In patients with unilateral TMJ pain, the frequency in those with disorder course≤1 month was higher than in those with other disease duration intervals ( P<0.01), while in patients with bilateral myalgia or TMJ pain plus unilateral or bilateral myalgia, the frequency in those with disorder course>3 years was higher than in those with other disease duration intervals( P<0.01). In patients with unilateral TMJ pain, the frequency was higher in those having open-and-close and/or lateral excursion and/or protrusion pain ( P<0.01). In patients with unilateral myalgia and bilateral myalgia, the frequency was higher in those having tenderness ( P<0.01). The frequency of TMJ space changes in male patients was higher than females and the frequency of hyperosteogeny and resorption in females were higher than males ( P<0.05). The frequency of TMJ space changes and developmental problems were higher in patients aged 16 to 35 years, while the frequencies of hyperosteogeny, bone resorption and cystis in those over 56 years were higher than other ages ( P<0.01). The frequency of TMJ space changes in patients with disorder course≤1 month was higher than in those with other disease duration intervals ( P<0.01), while the frequency of hyperosteogeny was higher in patients with disorder course>3 years ( P<0.01). Conclusions:The male to female ratio in the present patients with orofacial pain of TMD was about 1 to 2. Most of the patients visited hospital within half a year after the disorders occurred. The pattern and site of the orofacial pain, signs on TMJ CT images showed some distribution regularities in views of gender, age and disorder course.

More efficient drug delivery system and formulation with less adverse effects are needed for the clinical application of broad-spectrum antineoplastic agent doxorubicin (DOX). Here we obtained outer-membrane vesicles (OMVs), a nano-sized proteoliposomes naturally released by Gram-negative bacteria, from attenuated and prepared doxorubicin-loaded O0MVs (DOX-OMV). Confocal microscopy and distribution study observed that DOX encapsulated in OMVs was efficiently transported into NSCLC A549 cells. DOX-OMV resulted in intensive cytotoxic effects and cell apoptosis as evident from MTT assay, Western blotting and flow cytometry due to the rapid cellular uptake of DOX. In A549 tumor-bearing BALB/c nude mice, DOX-OMV presented a substantial tumor growth inhibition with favorable tolerability and pharmacokinetic profile, and TUNEL assay and H&E staining displayed extensive apoptotic cells and necrosis in tumor tissues. More importantly, OMVs' appropriate immunogenicity enabled the recruitment of macrophages in tumor microenvironment which might synergize with their cargo DOX . Our results suggest that OMVs can not only function as biological nanocarriers for chemotherapeutic agents but also elicit suitable immune responses, thus having a great potential for the tumor chemoimmunotherapy.

Objective To clarify the applied anatomy of Chinese female breasts,to improve the breast reduction mammoplasty,and to compare the quality of life in women with symptomatic macromastia before and after reduction mammoplasty with the modified round block technique.Methods The blood supply and innervation of the nipple-areolar complex were dissected in 6 Chinese adult females (12 breast specimens).Special attention was paid to the Würinger horizontal septum and the medial and lateral ligaments.The specific beneficial effects of reduction mammoplasty were evaluated with the modified round block technique,and a general questionnaire the Short Form-36 Health Survey Questionnaire (SF-36) was used in this study,which has good reliability and validity.The scores of the patients before and after the surgery were collected respectively.Results In 12 breast specimens,there existed Würinger horizontal septum and the medial and lateral ligaments.The blood supply and nerve innervation of nipple-areolar complex went along Würinger horizontal septum.In all the patients enrolled,SF-36 showed significant higher quality of life after the operation with regard to 7 of 8 investigated domains.Role of emotion increased most significantly.Increased self-esteem and increased personal and public self-consciousness after surgery were observed.Conclusions The incidence of postoperative complications is reduced after using the modified round block technique.Patients have a higher degree of satisfaction overall.These data are further evidence that breast hypertrophy is not solely an esthetic problem.The reduction mammoplasty with the modified round block technique is an ideal technique.