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@#Abstract: In the present study, the compound XL-12 from our previous work was utilized as a lead compound. Through the optimization of the terminal phenyl ring, 12 target compounds were designed and synthesized. The structures of all target compounds were confirmed by 1H NMR, 13C NMR, and H RMS. In vitro enzyme activity assay showed that most compounds demonstrated significant inhibitory activity toward Bruton’s tyrosine kinase (BTK) and Janus kinase 3 (JAK3). Among them, compound I-3 exhibited moderate cell proliferation inhibitory activity toward Daudi cells and BaF3-JAK3 cells. In the evaluation of anti-inflammatory activity in vitro, compound I-3 could effectively inhibit the production of inflammatory factors IL-6; besides, it exhibited superior anti-inflammatory activity compared to ibrutinib in xylene-induced ear swelling model in mice.
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Objective To assess the nutritional status of vitamin D and associated factors among adults of six ethnic minority groups native to Yunnan Province,and provide evidence for policy making.Methods Between May 2019 and August 2020,a total of 690 adults were selected from Jinuo,Bulang,Jingpo,Deang,Achang and Pumi ethnic groups according to the sex and age composition in the 6th national census.A questionnaire survey and an anthropometric examination were conducted by trained health workers,and serum 25(OH)D levels were determined with high-performance liquid chromatography-tandem mass spectrometry.Results The median of serum 25(OH)D was 28.7(P25~P75∶24.3~33.8)ng/mL,and the prevalence of vitamin D sufficiency,insufficiency and deficiency were 44.2%、47.5%and 8.3%,respectively.There were significant differences in serum 25(OH)D levels among the six ethnic groups(χ2=139.29,P<0.01).Multivariate logistic regression showed that ethnic groups living in higher latitude areas(Pumi,Jingpo,Deang,and Achang),women,and those whose BMI≥24.0 were more likely to be vitamin D insufficient or deficient.Conclusion More than half of the ethnic adults suffer from vitamin D malnutrition which also varies across ethnicities.Further surveillance and interventions among key areas and populations are needed.
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Objective To explore the eradication rate of human papillomavirus(HPV)and gestational outcome of patients with high-grade squamous intraepithelial disease of the cervix(HSIL)after loop electrosurgical excision procedure(LEEP)by transvaginal dissection of the vesicorectal form the cervix.Methods A total of 53 patients treated with LEEP by transvaginal dissection of the vesicorectal form the cervix in Obstetrics and Gynecology Hospital,Fudan University from Jan to Dec,2019 were investigated.Clinical information of cervical cytological examination,HPV test and cervical biopsy under colposcopy were followed up for 6,12 and 24 months post-LEEP were collected.HPV infection in these 53 patients were compared before and after LEEP surgery.The rate of successful fertility of the cohort,the HPV conversion rate of patients with hysterectomy and LEEP done were compared.The association between the pathological type and positive surgical margin and the association between HPV infection type and positive surgical margin were analyzed.Results HPV infection rate of was 94.3%(50/53)and the proportion of HPV16 and/or 18 infection was 75.5%(40/53).Mono-HPV infection rate(69.8%,37/53)was significantly higher than mixed HPV infection rate(22.7%,13/53).Thirty-eight patients(71.7%)were found with positive surgical margin in previous LEEP operation.Fifteen patients had recurrence(28.3%)and 40 patients(75.5%)successfully delivered baby after surgery.Postoperative pathology was mainly HSIL,accounting for 66%(30/53),and 28.3%patients(15/53)had no pathological change.Forty cases had satisfying fertility-conservative operation outcome with negative surgical margin,and 38 patients eradicated HPV infection after LEEP,which took up 95%of patients with satisfying fertility-conservative operation.There was no significant difference of positive resection margin rate in between groups of HPV16/18 infection and other types.Five cases had successful delivery(12.5%,5/40)with 1 case of vaginal delivery and 4 cases of cesarean section.Among these 5 cases,3 cases undertook preventive cervical cerclage,with 1 case of vaginal delivery and 2 cases of cesarean sections.Conclusion HPV eradication rate and surgical outcome could be significantly improved by LEEP with transvaginal dissection of the vesicorectal from the cervix,which satisfied the fertility preservation of females at reproductive age.
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Objective To study the anti-osteoporotic effect of different concentrations of hesperidin on ovariectomized rat model of osteoporosis(Ovariectomy,OVX)by reducing inflammatory molecules and oxidative stress response mechanism and the relationship between hesperidin and dose.Methods SD female rats were randomly divided into OVX group and Sham group,and OVX operation and sham operation were performed respectively.OVX group was randomly divided into 5 groups with 6 rats in each group,and 6 rats in Sham group were randomly selected as normal control group.They were Sham group(Sham rats+1%CMC suspension),control group(OVX rats+1%CMC suspension),HP1 group(OVX rats+5 mg·kg-1 HP),HP2 group(OVX rats+10 mg·kg-1 HP),HP3 group(OVX rats+20 mg·kg-1 HP)and AN group(OVX rats+2.5 mg·kg-1 AN).After 4 weeks of ovariectomized or sham operation,the drug was given by oral administration every morning for 10 weeks.After 10 weeks of administration,the change of body weight of rats was measured.Before the rats were killed,the serum of abdominal aorta was obtained and placed in the specimen cabinet at-20℃,the levels of Ca2+ and P5+,the levels of inflammatory factors TNF-α,IL-6 and IL-1β,and the levels of periosseous transition markers ALP,ACP,β-CTx and OC were also measured.After the rats were killed,the left femur was also placed in the specimen cabinet at-20℃.After treatment,the levels of oxidative stress factor TRARS and antioxidant enzymes GSH,GST,GR,GPx and CAT in the left femur were measured,and the bone mineral density,Young's modulus,maximum load,energy absorption and maximum stress in the middle part of the left femur were measured,and the expression level of SIRT1 gene was obtained.Results Compared with the control group,after 10 weeks of treatment with different concentrations of HP,the weight gain was significantly reduced(P<0.001),the levels of Ca2+ and P5+ in OVX rats were significantly decreased(P<0.001),and the levels of periosseous transition markers ALP,ACP,β-CTx and OC were significantly decreased(P<0.001).It significantly increased bone mineral density,Young's modulus,maximum load,energy absorption,maximum stress and stiffness(P<0.001),significantly decreased the level of OVX-induced thiobarbituric acid reactive substances and increased the levels of antioxidant enzymes GSH,GST,GR,GPx and CAT(P<0.001),and significantly decreased the levels of inflammatory molecules TNF-α,IL-6 and IL-1β(P<0.001).The expression level of SIRT1 gene was significantly decreased(P<0.001).Compared with the control group,the above parameters in the high concentration HP group were significantly different from those in the control group(P<0.001).Conclusion It is suggested that hesperidin can inhibit osteoporosis by reducing pro-inflammatory cytokines and oxidative stress in ovariectomized rats in a concentration-dependent manner.
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Objective To investigate the application of Rotarex mechanical thrombectomy system in lower extremity arterial thrombosis and to evaluate its clinical efficacy.Methods The clinical data of 61 patients(71 limbs,35 cases in acute phase,21 cases in subacute phase and 5 cases in chronic phase)with lower extremity arterial thrombosis treated with Rotarex were analyzed retro-spectively.Distal protective device was used in patients with poor distal artery outflow.High pressure saline was used during the pro-cedure and stent was used in patients with flow-limiting dissection.Catheter aspiration was performed in patients with distal artery embo-lization.Anticoagulant therapy was used in patients with thromboembolism and dual antiplatelet therapy was used in patients with in-situ thrombosis.Postoperative follow-up was performed with color Doppler ultrasound or computed tomography angiography(CTA)at 1 month,3 months and 6 months.Results Fifty-nine cases were treated with 6F Rotarex catheters and 2 cases were treated with 8F Rotarex catheters.Distal protective device was used in 10 cases,balloon dilation was performed in 49 cases and stent was used in 5 cases.Catheter aspiration was performed in 10 cases.Vessel rupture occurred in 4 cases,among whom 3 cases were successfully treated with the method of balloon compression and 1 case was treated with covered stent.Severe adverse events occurred in 4 cases and perioperative toe amputation was performed in 7 cases.Follow-up time was 3 to 6 months(mean 4.9 months).Lower extremity ischemic event occurred in 1 case at 6th month follow-up and was treated with stent.No other lower extremity ischemic events occurred in the course of follow-up.Conclusion For the treatment of lower extremity arterial thrombosis,Rotarex mechanical thrombectomy sys-tem has the advantages of minimally invasion,rapid and high efficiency.Combined with the therapy of catheter aspiration and stent place-ment,vascular patency can be further maintained and the lower extremity ischemic symptoms can be quickly relieved.
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BACKGROUND:The incidence of high lumbar disc herniation in elderly patients with osteoporosis is increasing.The changes in lumbar overall mechanical strength and biomechanical properties of adjacent vertebrae after conventional posterior approach decompression and interbody fusion have not been clarified.Finite element analysis has great value in the field of biomechanics because of its advantages of non-invasiveness,high repeatability and accuracy. OBJECTIVE:To explore the establishment of a finite element model of senile osteoporotic L3/4 lamina decompression using finite element analysis and intervertebral fusion spine,and to evaluate the biomechanical status of the internal fixation complex of bones under bending motion in elderly patients with osteoporosis. METHODS:Mimics 21.0 was used to extract the DICOM data of the spine CT to establish the 3D bony structure of the lumbar spine(T12-L5),which was imported into Geomagic wrap 2017.The L3/4 full lamina decompression model was established after redrawing the mesh,deleting the nails,cutting the model,filling the cavity,detecting and editing the contour line,constructing curved surfaces and grids,fitting curved surfaces and other operations.Solidworks 2017 was used to construct pedicle screws,connecting rods,and intervertebral fusion cages,which were assembled into the L3/4 full lamina decompression model.Intervertebral discs and articular process cartilage and other structures were established through operations such as stretching,isometric surfaces,moving and copying entities.ANSYS Workbench 17.0 was utilized for material assignment,simulating spinal ligaments,meshing,applying force and limiting boundary conditions.A complete osteoporotic L3/4 laminar decompression and intervertebral fusion spine finite element model was established.The stress,strain and displacement cloud diagram of the L3/4 lamina decompression and intervertebral fusion full lumbar spine finite element model were observed under simulated bending conditions. RESULTS AND CONCLUSION:(1)In terms of the stress cloud diagram:The T12-L1 vertebra had the highest average stress value;L2 dropped by 24%;L3 dropped by 55%,and L4-5 dropped by about 80%.The stress concentration in the L4/5 articular process area was the highest,followed by L2/3,and lighter in L1/2 and T12/L1.The stress concentration at the junction of the screw and the connecting rod was obvious,followed by the screw at the entrance and exit of the pedicle.(2)In terms of strain and displacement cloud map:The strain degree of L4/5 and L2/3 articular process was the highest;the strain degree of T12/L1 and L1/2 was the second,and the L3/4 segmental fusion cage,pedicle screw and connecting rod had no any visible deformation.The intervertebral discs of all segments showed great deformation.(3)It is concluded that the cooperative operation of multiple software can successfully construct a finite element model of the spine with L3/4 lamina decompression and intervertebral fusion in elderly patients with osteoporosis.Elderly patients after lumbar spine surgery can tolerate forward flexion,confirming that L3/4 laminar decompression and intervertebral fusion can maintain the shape of the spine and ensure the stability of the spine,but it is necessary to be alert to the occurrence of thoracolumbar stress fractures and adjacent spondylopathy.
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BACKGROUND:Thromboelastography plays an important role in identifying the hypercoagulable state of blood and thrombosis in humans.Recent studies have shown a correlation between an increase in mean platelet volume and thrombosis.We can therefore ask whether the combined diagnosis of thromboelastography and mean platelet volume is a more accurate predictor of thrombosis. OBJECTIVE:To predict the status of blood and the occurrence of thrombosis after total knee arthroplasty by means of mean platelet volume combined with thromboelastography. METHODS:One hundred and twenty patients who underwent unilateral total knee arthroplasty between May 2015 and March 2022 were collected.Patients were divided into 60 patients in the thrombosis group and 60 patients in the control group based on ultrasound findings on postoperative day 7.Whole blood cell and thromboelastography were performed 1 day before,1 and 7 days after surgery,respectively.Multifactorial analysis was used to investigate independent predictors of thrombosis after total knee arthroplasty.The receiver operating characteristic curve and area under the curve were measured in the subjects. RESULTS AND CONCLUSION:Mean platelet volume correlated most strongly with maximum amplitude,followed by coagulation angle.Mean platelet volume and coagulation angle on postoperative day 1 were independent predictors of thrombosis.Mean platelet volume tended to rise and then fall in patients with thrombosis.The best critical value for mean platelet volume to predict thrombosis was 10.73 fL.The area under the receiver operating characteristic curve of subjects was 0.665(95%CI:0.568-0.762,P<0.05];whereas the area under the receiver operating characteristic curve for subjects using mean platelet volume combined with coagulation angle was 0.815(95%CI:0.750-0.879,P<0.05).In addition,the maximum amplitude,coagulation angle,coagulation index and mean platelet volume were significantly higher in the thrombosis group than in the control group postoperatively(P<0.05).The results suggest that the mean platelet volume can reflect the hypercoagulable state of blood after surgery,and the combination of mean platelet volume and coagulation angle on day 1 after total knee arthroplasty can improve the prediction of thrombosis.
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BACKGROUND:Patients with femoral intertrochanteric fracture may have nutritional risks during proximal femoral nail anti-rotation surgery,and a clinical predictive model is established based on nutritional assessment tools. OBJECTIVE:To establish the nomogram of the nutritional risk prediction model for patients with intertrochanteric fracture after proximal femoral nail anti-rotation fixation and evaluate the accuracy of the model. METHODS:From December 2018 to July 2022,patients with femoral intertrochanteric fractures who underwent proximal femoral nail anti-rotation fixation in First Department of Orthopedics,Second Affiliated Hospital of Baotou Medical College were selected as the study subjects.The nutritional risk status of patients was assessed using nutritional risk screening 2002.Logistic regression was used to build the model.The receiver operating characteristic curve,Calibration plot calibration curve,and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the discrimination,calibration and clinical applicability of the prediction model.The model was visualized using Nomogram diagrams. RESULTS AND CONCLUSION:(1)Seventy-six patients were included according to the inclusion criteria.The incidence of nutritional risk was 80%after being assessed using nutritional risk screening 2002.(2)The results of Logistic regression analysis demonstrated that age≥77 years old,body mass index<22.80 kg/m2,upper arm circumference<25.01 cm,hemoglobin<98.51 g/L,albumin<31.61 g/L,and prealbumin<138.56 g/L were all independent risk factors for nutritional risk(P<0.05).(3)The area under the receiver operating characteristic curve was 0.919(95%CI:0.843-0.994).(4)The results of the Hosmer-Lemeshow goodness-of-fit test displayed that nutritional risk prediction value was high.(5)It is concluded that the nutritional risk assessment model constructed in this study has a good degree of discrimination and calibration,and has a certain predictive ability,which can be used as a reference tool for nutritional risk assessment of patients after proximal femoral nail anti-rotation fixation.
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BACKGROUND:Clinically,the most dangerous and serious complication of artificial joint replacement is periprosthetic infections.It is urgent to find a way to prevent periprosthetic infections after artificial joint replacement. OBJECTIVE:To study the effect of povidone-iodine on muscle,blood vessel,fat and bone of rabbits after immersion and flushing. METHODS:Forty male New Zealand rabbits aged 10 weeks were selected.The left hind leg of each rabbit served as the experimental group and the right hind leg served as the control group.After anesthesia,the hind limbs of each rabbit were cut open to expose the muscle,blood vessels,fat and bone.The control group was soaked and flushed with normal saline inside the surgical incision,while the experimental group was soaked and flushed with povidone-iodine inside the surgical incision.After being soaked in povidone-iodine for 0,1,3,5 minutes,10 rabbits were randomly selected and executed to collect wound tissue samples.The samples were made into pathological slices for hematoxylin-eosin staining observation as well as statistical analysis and comparison of cell counts. RESULTS AND CONCLUSION:Compared with the control group,the muscle,blood vessels,fat and bone after immersion and flushing with povidone-iodine showed no obvious difference in cell structure,morphology and number under microscope.The paired t-test was used to explore the difference between the control and experimental groups,and the paired data did not show any difference(P>0.05).It is suggested that povidone-iodine shows no significant difference from normal saline after immersion and flushing of rabbit tissues such as muscle,blood vessels,fat and bone,indicating that povidone-iodine solution as an intra-incisional antiseptic is safe and effective.
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BACKGROUND:Previous studies on the effects of valgus and varus angles of tibial component on short-term postoperative outcomes after mobile bearing unicompartmental knee arthroplasty have been reported in and outside China.However,there are few reports on the effect of the valgus and varus angles of tibial component on short-term postoperative outcomes after fixed bearing unicompartmental knee arthroplasty. OBJECTIVE:To investigate the effect of valgus and varus angles of tibial component on short-term clinical outcomes in patients with medial knee osteoarthritis undergoing fixed bearing unicompartmental knee arthroplasty. METHODS:120 patients(122 knees)who underwent fixed bearing unicompartmental knee arthroplasty for medial knee osteoarthritis in Department of Orthopedic Surgery,Affiliated Hospital of Xuzhou Medical University from August 2020 to January 2023 were selected as the study subjects.Two physicians measured the varus angle of femoral prosthesis,valgus and varus angles of tibial prosthesis,flexion and extension angles of femoral prosthesis,and posterior inclination angle of tibial prosthesis after unicompartmental knee arthroplasty based on postoperative X-ray.After excluding the influence of the other three angles,the measurement results of the tibial component varus angle were divided into three groups:<-2°,-2° to 2°,>2°,which were denoted as groups 1,2,and 3,respectively.The range of knee motion,the hospital for special surgery knee score,the American knee society score,and forgotten joint score were recorded and compared before and after the operation. RESULTS AND CONCLUSION:(1)A total of 120 patients(122 knees)were enrolled in this study.They were divided into three groups according to the size of the valgus and varus angles of the tibial prosthesis after operation:37 patients in the first group,60 patients in the second group,and 23 patients in the third group.There was no significant difference between the three groups in terms of baseline information such as age,gender,and side of surgery(P>0.05).(2)Patients were followed up for 3-30 months after arthroplasty.(3)The hospital for special surgery knee score of the second group was higher than that of the first group(P=0.015)and the third group(P=0.012).The American knee society score of the second group was significantly higher than that of the first group(P=0.014)and the third group(P<0.001).The forgotten joint score of the second group was higher than that of the first group(P=0.033)and the third group(P=0.016).(4)After fixed bearing unicompartmental knee arthroplasty,when the valgus angle of tibial prosthesis was-2° to 2°,which can achieve better short-term clinical results,the degree of prosthesis self-realization is higher.
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Objective:To investigate the prevalence of adult skeletal fluorosis caused by drinking tea-type endemic fluorosis in Yushu Tibetan Autonomous Prefecture (hereinafter referred to as Yushu Prefecture), Qinghai Province, and provide scientific basis for prevention and control of the disease.Methods:In August 2021, one village was selected as a survey site in six counties (cities) in Yushu Prefecture, including Nangqian, Chindu, Yushu, Zadoi, Qumarlêb, and Zhiduo. Drinking water samples and 10 brick tea samples were collected from each village to determine the fluoride content in water and brick tea; at least 100 permanent residents aged ≥ 25, who had a habit of drinking brick tea and had lived in the local area for more than 5 years, were selected for X-ray imaging to examine the prevalence of adult skeletal fluorosis.Results:A total of 75 samples of residential drinking water were collected, with a fluoride content of (0.21 ± 0.05) mg/L, ranging from 0.11 to 0.34 mg/L; 60 samples of brick tea, with a fluoride content of (626.70 ± 157.27) mg/kg, ranging from 324.00 to 2 102.00 mg/kg. A total of 1 136 adults were examined, and 318 cases of skeletal fluorosis were diagnosed, with a detection rate of 27.99%. Among them, the detection rates of mild, moderate, and severe skeletal fluorosis were 20.95% (238/1 136), 6.07% (69/1 136), and 0.97% (11/1 136), respectively, with mild symptoms being the main. The detection rates of skeletal fluorosis in males and females were 29.09% (121/416) and 27.36% (197/720), respectively, with no statistically significant difference between the gender (χ 2 = 0.39, P = 0.533). Comparison of the skeletal fluorosis in different gender, the differences were statistically significant (χ 2 = 22.31, P < 0.001). The detection rates of skeletal fluorosis in the age groups of 25 - 35, 36 - 45, 46 - 55, 56 - 65, 66 - 75, and ≥76 years old were 6.86% (7/102), 22.37% (51/228), 24.02% (92/383), 37.44% (73/195), 43.48% (70/161), and 37.31% (25/67), respectively. The differences between the groups were statistically significant (χ 2 = 59.84, P < 0.001). Moreover, there was a statistically significant difference in the composition of skeletal fluorosis among different age groups ( H = 37.66, P < 0.001). The Spearman correlation analysis results showed that the severity of adult skeletal fluorosis was positively correlated with age ( r = 0.34, P < 0.001). Conclusions:There is a certain degree of prevalence of adult skeletal fluorosis in Yushu Prefecture. And as age increases, the condition of skeletal fluorosis becomes more severe.
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Objective To investigate the screening and prevalence of tuberculosis among freshmen in different schools in Baoding City,and provide reference for tuberculosis control in schools.Methods Screening data of tu-berculosis and tuberculin test(PPD)of freshmen from 156 schools in different regions of Baoding City from Septem-ber 2021 to March 2022 were collected.PPD screening results of students from different regions and different school stages were analyzed and compared.Results A total of 68 177 freshmen from 156 schools were investigated for suspected symptoms and close contact history of pulmonary tuberculosis.PPD screening was conducted on 63 939 students.13 821 students were PPD positive,with a positive rate of 21.62%.3 083 students were strongly posi-tive,with a strong positive rate of 4.82%.15 cases of tuberculosis were found,and the reported incidence was 23.46/100 000.PPD positive rate and strong positive rate as well as incidence of tuberculosis in students in different school stages presented statistically significant differences(all P<0.01).Positive rate and strong positive rate in students in different school stages showed upward trends(all P<0.01).PPD positive rate and strong positive rate of students from schools in plain and mountainous areas presented statistically significant differences([22.28%vs 17.89%];[4.85%vs 3.62%],both P<0.01).PPD positive rate and strong positive rate between students from boarding junior school and non-boarding junior school were significantly different,respectively([23.94%vs 21.60%];[5.07%vs 3.56%],both P<0.01).Conclusion It is necessary to strengthen tuberculosis screening and health education for freshmen,especially those from boarding schools in plain areas,screening latent Mycobac-terium tuberculosis infection as early as possible,take corresponding measures to prevent and control the spread of tuberculosis,and reduce the risk of tuberculosis.
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Objective:To explore the clinical application and triage management value of using blood circulating cell-free DNA (cfDNA) (cysteine dioxygenase type 1 gene, CDO1, and Homeobox protein A9 gene, HOXA9) hypermethylation level to detect and diagnose ovarian cancer.Methods:A case-control study was conducted on patients who went for surgery at Chengdu Womens and Childrens Central Hospital from November 2022 to October 2023. Blood samples were collected before surgery for evaluation of cancer antigen 125 (CA125), human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA) score, and DNA methylation testing. The basic clinical information, biomarkers, and transvaginal ultrasound (TVS) information were collected simultaneously. Information from a total of 151 patients was collected, including 122 cases with benign pathology and 29 ovarian cancer cases. The pathologic diagnosis of ovarian tissue was defined as the gold standard. The multivariate logistic regression analysis was used to identify high-risk factors for ovarian cancer. The clinical efficacy of DNA methylation detection for ovarian cancer was analyzed using the area under curve (AUC).Results:The results showed that the age, menopausal status, CA125 and HE4 detection, ROMA score, positivity rate of CDO1 gene and HOXA9 gene single or combined testing in ovarian cancer patients were higher than those in the benign group and showed significant differences ( P<0.05). Among these detection protocols, the AUC of CDO1 and HOXA9 dual gene methylation testing for ovarian cancer was the highest at 0.936 (95% CI, 0.878-0.994), with 89.7% (95% CI 73.6%-96.4%) sensitivity and 97.5% (95% CI 93.0%-99.2%) specificity, respectively. The positive detection rate of CDO1 and HOXA9 dual gene methylation in early ovarian cancer FOGO I-II stage is 12/14 higher than other tests. Conclusion:Blood cfDNA methylation detection, a simple, non-invasive, and highly sensitive detection method, is superior to the current ovarian cancer testing in the risk assessment and early detection.
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ObjectiveTo comprehensively evaluate the clinical value of Feilike mixture and provide a basis for the allocation of medical resources, rational drug use, and hospital procurement and supply of Chinese patent medicines. MethodWith the data from available studies and provided by drug manufacturers, the methods of evidence-based medicine, pharmacoeconomics, and health technology assessment were employed to construct a multi-criteria decision-making analysis framework from the "6+1" dimensions of safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine (TCM). The clinical evidence and value evaluation software of Chinese patent medicine, CSCv2.0, was used to comprehensively evaluate the clinical value of Feilike mixture. ResultBased on the existing clinical evidence, the following results were obtained. ① Safety: Multi-sources of evidence showed that Feilike mixture had little known risk and sufficient evidence, with the safety rated as grade A, which indicated good safety. ② Effectiveness: The systematic review and Meta-analysis showed that Feilike mixture combined with conventional Western medicine in the treatment of bronchitis shortened the time to disappearance of cough compared with conventional Western medicine alone, with the evidence rated as grade B by the Grading of Recommendations Assessment, Development, and Evaluations (GRADE) system, which indicated high effectiveness. ③ Economy: From the perspective of health system, Feilike mixture combined with conventional Western medicine was more economical than conventional Western medicine alone, and the quality evaluation of pharmacoeconomics rated the economy as grade B. ④ Innovation: Feilike mixture combined with conventional Western medicine improved the clinical treatment effect and had innovation advantages compared with similar drugs. From the aspects of cultivation, identification of medicinal materials, and production, the sufficient supply and safety of medicinal materials can be ensured for Feilike mixture. This medicine was rated as grade B in terms of the medicinal material quality, preparation technology, and patents, which indicated good innovation. ⑤ Suitability: According to the results of the questionnaire survey, the usage of Feilike mixture was easy to be mastered and accepted by doctors and nurses, without special administration time, complex personalized treatment, and special technical and management requirements. It is convenient for patients to use, with convenient supply and storage, and weak influences of policy, publicity, and drug information. Therefore, the suitability of Feilike mixture was rated as grade B. ⑥ Accessibility: Among the similar Chinese patent medicines, Feilike mixture had a moderate price, high production capacity, wide sales coverage, wide coverage of hospitals, sustainable supply of medicinal materials, and low costs of treatment for acute bronchitis, with the accessibility rated as grade A. ⑦ TCM characteristics: Feilike mixture is composed of Scutellariae Radix, Peucedani Radix, Stemonae Radix, Gentianae Rhodanthae Herba, Scleromitrion diffusum, Firmiana platanifolia Radix, and Aster ageratoides, with reasonable compatibility. This formula is derived from the medical experience of Miao ethnic group, with rich experience in human use and the TCM characteristics rated as grade B. According to the evaluation results in the "6+1" dimensions, Feilike mixture was evaluated as class B, with a high clinical value. ConclusionAccording to the existing clinical evidence, compared with conventional Western medicine alone, Feilike mixture combined with conventional Western medicine demonstrates a high clinical value and prominent TCM characteristics in the treatment of acute bronchitis with phlegm-heat invading lung. It is suggested that it should be translated into the basic clinical drug management policy results according to the conditions.
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Thirty-one phenolic constituents were isolated and purified from the 95% ethanol extract of Sanguisorbae Radix by using various chromatographic techniques, including macroporous resin, silica gel, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated by physicochemical properties, spectroscopic data (MS and NMR) and electronic circular dichroism (ECD) spectra, and identified as 3-methoxyl-2S,3S-epoxyflavanone (1a), 3-methoxyl-2R,3R-epoxyflavanone (1b), longifoin B (2), longifoin C (3), eriodictyol (4), naringenin (5), liquiritigenin (6), 5,3ʹ-dihydroxy-7,4ʹ-dimethoxyflavanone (7), naringenin-7-O-β-D-glucopyranoside (8), dihydroquercetin (9), dihydrokaempferol (10), (-)-garbanzol (11), (2R,3R)-4-methoxyl-distylin (12), kaempferol (13), quercetin (14), α,4,2′,4′-tetrahydroxydihydrochalcone (15), phloretin (16), (+)-catechin (17), ethyl (+)-cyanidan-3-ol-8-carboxylate (18), phyllocoumarin (19), methyl 3-methoxy-4,5-dihydroxybenzoate (20), 4,5-dimethoxy-3-hydroxybenzoic acid methyl ester (21), 3,4′-di-O-methylellagic acid (22), 3,4,3′-O-trimethylellagic acid (23), 3,3ʹ,4ʹ-O-trimethylellagic acid-4-O-β-D-xyloside (24), (3R)-thunberginol C (25), resveratrol (26), 1-hydroxypinoresinol (27), (7S,8S)-3-methoxy-3′,7-epoxy-8,4′-oxyneoligna-4,9,9′-triol (28), emodin-8-O-β-D-glucoside (29), phloracetophenone (30) and 4-(4′-hydroxyphenyl)-butan-2-one (31). Among them, compound 1a and 1b is a pair of new flavonoid enantiomers, compounds 2 and 3 are a pair of new epimers, while compounds 4, 5, 6, 9, 10, 13, 16 and 26 were obtained from S. officinalis for the first time, compounds 7, 8, 27, 30 and 31 were isolated for the first time from the S. officinalis genus, and compounds 11, 12, 15, 18, 19, 25, 28 and 29 were isolated for the first time from the Rosaceae. The antioxidant activities of compounds 1-24 were evaluated by activating the Nrf2 transcriptional pathway, which were measured by the dual-luciferase reporter gene assay in 293T cells. Compounds 4, 6-10, 12, 14, 17, 19, 20 and 22-24 showed significant Nrf2 agonistic effect compared with the control group at 25 μmol·L-1, which provided reference for the research of their antioxidant activity.
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OBJECTIVE To optimize ethanol extraction process of Yihuang powder. METHODS An orthogonal experiment was designed by reflux extraction with ethanol volume fraction, liquid-to-material ratio, and extraction time as investigation factors. The parameters used were the contents of hesperidin, nobiletin, tangeretin, gallic acid, chebulagic acid, chebulinic acid, liquiritin, glycyrrhizin, eugenol, and the paste-forming rate. The analytic hierarchy process (AHP) was used to calculate the comprehensive score. The optimal ethanol extraction process parameters of Yihuang powder were determined by verifying the results predicted by orthogonal experiment and genetic algorithm (GA)-back propagation neural network (BP neural network). RESULTS The optimal ethanol extraction process parameters, as optimized by orthogonal experiment, were as follows: ethanol volume fraction of 60%, liquid-solid ratio of 14∶1 (mL/g), extraction time of 90 min, and extraction for 2 times. The comprehensive score obtained by verification was 79.19. Meanwhile, the optimal ethanol extraction process parameters, optimized by GA-BP neural network, were ethanol volume fraction of 65%, liquid-solid ratio of 14∶1 (mL/g ), extraction time of 60 min, and extraction for 2 times. The comprehensive score obtained by verification was 85.30, higher than the results obtained from orthogonal experiment. CONCLUSIONS The optimization method of orthogonal experiment combined with GA-BP neural network is superior to the traditional orthogonal experiment optimization method. The optimized ethanol extraction process of Yihuang powder is stable and reliable.
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Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.
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AIM To prepare the nanosuspensions of naringenin phospholipids complex,and to investigate their in vivo pharmacokinetics.METHODS High-pressure homogenization method was applied to preparing the nanosuspensions of phospholipids complex.With stabilizer type,stabilizer-phospholipids complex consumption ratio,homogeneous pressure and homogeneous frequency as influencing factors,particle size,PDI and Zeta potential as evaluation indices,the formulation was optimized by single factor test.The morphology was observed under transmission electron microscope,after which X-ray powder diffraction analysis was performed,solubility,oil-water partition coefficient,dissociation rate of phospholipids complex and accumulative release rate were determined.Twenty-four rats were randomly assigned into four groups and given intragastric administration of the 0.5%CMC-Na suspensions of naringenin and its phospholipids complex,nanosuspensions and nanosuspensions of phospholipids complex(30 mg/kg),respectively,after which blood collection was made at 0,0.25,0.5,1,1.5,2,3,4,5,6,8,10,12 h,HPLC was adopted in the plasma concentration determination of naringenin,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was determined to be 50 mg for naringenin consumption,PVP K30+TPGS(1 ∶ 1)as stabilizer,3 ∶ 1 for stabilizer-phospholipids complex consumption ratio,100 MPa for homogeneous pressure,and 10 times for homogeneous frequency,respectively.The obtained spherical-like or oval nanosuspensions of phospholipids complex demonstrated the average particle size,PDI and Zeta potential of(260.53±25.86)nm,0.160±0.024 and(-31.08±1.37)mV,respectively.Naringenin existed in the nanosuspensions of phospholipids complex in an anamorphous state,along with increased solubility,oil-water partition coefficient and dissociation rate of phospholipids complex,and the accumulative release rate reached more than 90%within 4 h.Compared with raw medicine and nanosuspensions,the nanosuspensions of phospholipids complex displayed shortened tmax(P<0.05)and increased Cmax,AUC0-t,AUC0-∞(P<0.05,P<0.01),the relative bioavailability was enhanced to 4.38 times.CONCLUSION The nanosuspensions of phospholipids can enhance naringenin's solubility and dissolution rate,and promote its in vivo absorption.
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AIM To investigate the protective effects and the mechanism of the Liuwei Dihuang Pills on mouse brain microvascular endothelial(bEnd.3)cells damaged by β-Amyloid protein1-40(Aβ1-40).METHODS CCK8 method was used to detect the effects of Aβ1-40 and medicated serum of Liuwei Dihuang Pills(MSLDP)on cell activity,and to screen the appropriate concentration.bEnd.3 cells of the control group,the Aβ1-40 group,the MSLDP+Aβ1-40 group and the MSLDP group had their low density lipoprotein-associated protein 1(LRP1),receptor for advanced glycation end products(RAGE),matrix metalloproteinase-2(MMP-2),MMP-9,scaffold protein zonule protein-1(ZO-1)detected by Western blot.bEnd.3 cells assigned into the control group,the Aβ1-40 group,the FPS-ZM1(RAGE inhibitor)+Aβ1-40 group and the FPS-ZM1+Aβ1-40+MSLDP group had their expressions of RAGE,MMP-9,MMP-2 and ZO-1 detected by Western blot as well.RESULTS The cell activity of bEnd.3,was dose-dependently decreased by Aβ1-40(P<0.01),but was protected by MSLDP(P<0.05,P<0.01).And 10 μmol/L Aβ1-40 and 10%MSLDP were selected for subsequent experiments.Compared with the control group,the Aβ1-40 group displayed increased protein expressions of RAGE,MMP-2 and MMP-9(P<0.01),decreased protein expressions of LRP1,ZO-1 and BDNF(P<0.05,P<0.01),and decreased fluorescence intensities of LRP1 and ZO-1(P<0.01).Compared with the Aβ1-40 group,the MSLDP group shared decreased expressions of RAGE,MMP-2,MMP-9 proteins and RAGE fluorescence intensity(P<0.05,P<0.01),and increased expressions of LRP1,ZO-1 and BDNF proteins,and the fluorescence intensity of LRP1 and ZO-1(P<0.05,P<0.01);the Aβ1-40+FPS-ZM1 group displayed decreased protein expressions of MMP-2,MMP9 and RAGE(P<0.05,P<0.01),and increased ZO-1 protein expression(P<0.05);and the Aβ1-40+FPS-ZM1+ MSLDP group displayed an even more decreased protein expressions of MMP-2,MMP9 and RAGE(P<0.01),increased ZO-1 protein expression(P<0.01)due to the the combination use of FPS-ZM1 and MSLDP.CONCLUSION Liuwei Dihuang Pills can protect the tight junction of bEnd.3 injured by Aβ1-40 and neurovascular units from Alzheimer's disease by alleviating the dysfunction of the blood-brain barrier via RAGE-mediated MMP-2/MMP-9 pathway inhibition.
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ObjectiveTo analyze the psychological resilience characteristics of visually impaired adolescents. MethodsFrom February to May, 2023, 13 visually impaired adolescents (average age of 16.5 years) from Nanjing Normal University of Special Education, Yangzhou Special Education School and Nanjing School for the Blind in Jiangsu, China were selected for semi-structured interviews with phenomenological method, and the interview data were sorted by theme analysis method. ResultsFour themes and twelve sub-themes were obtained; namely multiple sources of difficulties, including travel difficulties, learning difficulties, social difficulties and difficulties in daily life; need for external support, including insufficient family support, school support needs to be improved, need for peer support and insufficient social support; negative and positive adaptation coexist, including negative adaptation and positive adaptation; and negative coping and positive coping coexist, including positive coping and negative coping. ConclusionThe psychological resilience of visually impaired adolescents is characterized by multiple sources of difficulties, insufficient external support, coexistence of positive and negative adaptation, and coexistence of positive and negative coping. A joint family-school-society support system should be formed to reduce the source of their difficulties, and help them establish positive adaptation and positive coping methods, to enhance their psychological resilience.