ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

In order to investigate the mechanical response of lumbar vertebrae during gait cycle in adolescents with idiopathic scoliosis (AIS), the present study was based on computed tomography (CT) data of AIS patients to construct model of the left support phase (ML) and model of the right support phase (MR), respectively. Firstly, material properties, boundary conditions and load loading were set to simulate the lumbar vertebra-pelvis model. Then, the difference of stress and displacement in the lumbar spine between ML and MR was compared based on the stress and displacement cloud map. The results showed that in ML, the lumbar stress was mostly distributed on the convex side, while in MR, it was mostly distributed on the concave side. The stress of the two types of stress mainly gathered near the vertebral arch plate, and the stress of the vertebral arch plate was transmitted to the vertebral body through the pedicle with the progress of gait. The average stress of the intervertebral tissue in MR was greater than that in ML, and the difference of stress on the convex and convex side was greater. The displacement of lumbar vertebrae in ML decreased gradually from L1 to L5. The opposite is true in MR. In conclusion, this study can accurately quantify the stress on the lumbar spine during gait, and may provide guidance for brace design and clinical decision making.
Humans ; Lumbar Vertebrae/diagnostic imaging* ; Scoliosis/diagnostic imaging* ; Adolescent ; Gait/physiology* ; Biomechanical Phenomena ; Tomography, X-Ray Computed ; Stress, Mechanical ; Female ; Male

OBJECTIVE:To investigate the correlation of blood concentrations of tamoxifen (TAM) and its metabolites with endometrial hyperplasia in estrogen receptor(ER)-positive breast cancer patients. METHODS:A total of 69 patients with ER-posi-tive breast cancer selected from our hospital during Mar. 2015-Apr. 2016 received TAM (twice a day,one tablet each time) for more than 6 months. According to endometrial thickness,they were divided into abnormal hyperplasia group(40 cases)and normal group(29 cases). The steady state concentrations of TAM and its metabolites [4-OH-tamoxifen(OHT),N-demethylation tamoxifen (DMT),Endoxifen] were determined by HPLC-FLU. The correlation of blood concentration and other factors with endometrial thickness were investigated by Pearson test and multiple regression analysis. RESULTS:The medication time and Endoxifen steady state concentration in abnormal hyperplasia group were both significantly longer or higher than normal group,with statistical signifi-cance (P<0.05). There was no statistical significance in age,BMI,complication and steady state concentrations of TAM,OHT and DMT between 2 groups(P>0.05). The endometrial thickness was positively correlated with Endoxifen steady state concentra-tion and medication time(r=0.447,0.460,P<0.05). Using endometrial thickness(y)as dependent variable,medication time(x1) and Endoxifen steady state concentration(x2)as independent variable,multiple regression analysis was conducted. Multiple regres-sion equation was calculated as follows:y=2.436+0.123x1+0.082x2(F=12.610,r=0.526,P<0.05). CONCLUSIONS:Medication time and Endoxifen steady state concentration may be related to endometrial hyperplasia,which can provide reference for predicting TAM induced endometrial abnormal hyperplasia in ER-positive breast cancer patients.

Objective:To study the correlation between plasma concentration and clinical efficacy in newly diagnosed type 2 diabe-tes treated with nateglinide. Methods:On the basis of diet control and exercise, 73 cases of newly diagnosed type 2 diabetes received nateglinde therapy for 2 months. Adverse events were routinely monitored during the therapy. Fasting blood glucose(FBG), 2h post-prandial blood glucose(2h-PG), fasting C-peptide(F-CP), 2h C-peptide(P-CP) and glycosylated hemoglobin (HbA1c) were ob-served before and after the treatment. LC-MS was used to determine the plasma concentration of nateglinide on the last day of treat-ment. Results:FBG, 2h-PG, HbAlc and P-CP after the treatment had significant changes when compared with those before the treat-ment (P<0. 05). There was no significant difference in F-CP in spite of minor increase (P>0. 05). The difference in HbA1c and P-CP before and after the treatment both showed a significantly positive correlation with plasma concentration of nateglinide (P<0. 05). Conclusion:Nateglinide displays good clinical efficacy and safety in newly diagnosed type 2 diabetes, and its plasma concentration can be used to evaluate the pancreatic islets function and glucose-lowing effects.

Objective To investigate the clinical value of clinical application in diagnosis of prostate cancer (PCa) by prostate biopsy guided by rectal ultrasound contrast guided biopsy.Methods One hundred and ninety-eight patients with prostate in Punan Hospital of Pudong New District of Shanghai were investigated.According to different detection methods, the research objects were divided into two groups, the patients were performed with the ultrasound contrast guided biopsy as the imaging group (n =96), the patients with Doppler ultrasound guided biopsy as the ultrasonic group(n =102).The puncture Results were compared with pathological diagnosis.The positive rate of PCa and number of puncture needle were compared with the two puncture methods.The value of the application of the prostate biopsy guided by rectal ultrasound in diagnosis of prostate cancer was evaluated.Result One hundred and ninety-eight patients were all received pathological diagnosis,78 cases benign lesions, 120 cases were diagnosed as PCa.Thirty-six cases of benign lesions were confirmed by pathological biopsy, 60 case PCa.There were 42 cases of benign lesions in ultrasonic group, 60 case PCa.The positive rate of PCa in the imaging groupwas 62.5％ (60/96), the ultrasonic group was 58.82％ (60/102).There was no difference in Pca positive rate between the ultrasound group and the contrast group(x2 =0.104, P=0.747).The positive number of Pca in the imaging group was 28.50％ (17/60), the difference was statistically significant higher than that of the common group(18.80％ (11/60), P =0.001).The average of the patients in the imaging group was 8.19 needle,less than the ultrasonic group per capita 11.31 needle less.When f/tPSA less than or equal to 0.15, Pca positive rate of the contrast group was 46.55％ (27/55), higher than the ultrasonic group(9.30％ (4/43)), the difference was statistically significant (P =0.001);when f/tPSA more than 0.15, the positive rate of Pca in the contrast group was 92.11％ (35/38), less than the ultrasound group (94.92 (56/59)), the difference was not statistically significant (P =0.89).Anal pain, hematuria and hematochezia in contrast group (7.29％ (7/96), 2.08％ (2/96), 10.42％ (10/96)) were significantly less than the ultrasound group(22.55％ (23/102), 8.82％ (9/102), 23.53％ (24/102)), the difference was statistically significant (P =0.003,0.039,0.014).Conclusion Under the guidance of ultrasound contrast, rectal biopsy has important diagnostic value for prostate cancer.Under the premise of reducing the number of puncture needle,can improvethe positive rate of Pca, reduce the pain of patients and the occurrence of complications after puncture.When f/tPSAless than or equal to 0.15,puncture positive rate in contrast group is higher than the ultrasonic group, puncture effect is better.

Obj ective To invesyigaye yhe clinical effecy of differeny approaches in yhe yreay-meny of dysphagia in payienys wiyh cerebral syroke.Methods 1 12 syroke payieny were randomly di-vided inyo yhree groups.A group was yreayed wiyh swallowing yraining and acupuncyure records u-niyed wiyh elecyric syimulayion yherapy.B group was yreayed wiyh swallowing yraining uniyed wiyh elecyric syimulayion yherapy.C group was yreayed wiyh swallowing yraining merely.All groups were given drinking wayer yesy yo evaluaye swallowing funcyion on yhe hospiyalized day and yhe 2 1 sy day of yhe yreaymeny.Results The yoyal effecyive raye of A group was 93 .7%,B group was 78 .9%,C group was 70 .2%.The yoyal effecyive raye of A group is superior yo yhay of B and C groups wiyh sya-yisyically significany(P<0 .05 ).The difference was syayisyically significany comparing A group and B group(P<0.05).The difference was syayisyically significany in drinking wayer yesy score and swal-lowing funcyion score before and afyer yreaymeny of yhe yhree groups.The resulys revealed yhay yhe yhree meyhods could improve dysphagia of payienys,buy yhe overall effecy of A group was superior yo yhay of B and C group.Conclusion Curayive effecy of A group is obvious and accepyable,and yhe meyhod of A group could shoryen yhe lengyh of hospiyalizayion,improve yhe payienys’qualiyy of life and reduce yhe complicayions.

Obj ective To invesyigaye yhe clinical effecy of differeny approaches in yhe yreay-meny of dysphagia in payienys wiyh cerebral syroke.Methods 1 12 syroke payieny were randomly di-vided inyo yhree groups.A group was yreayed wiyh swallowing yraining and acupuncyure records u-niyed wiyh elecyric syimulayion yherapy.B group was yreayed wiyh swallowing yraining uniyed wiyh elecyric syimulayion yherapy.C group was yreayed wiyh swallowing yraining merely.All groups were given drinking wayer yesy yo evaluaye swallowing funcyion on yhe hospiyalized day and yhe 2 1 sy day of yhe yreaymeny.Results The yoyal effecyive raye of A group was 93 .7%,B group was 78 .9%,C group was 70 .2%.The yoyal effecyive raye of A group is superior yo yhay of B and C groups wiyh sya-yisyically significany(P<0 .05 ).The difference was syayisyically significany comparing A group and B group(P<0.05).The difference was syayisyically significany in drinking wayer yesy score and swal-lowing funcyion score before and afyer yreaymeny of yhe yhree groups.The resulys revealed yhay yhe yhree meyhods could improve dysphagia of payienys,buy yhe overall effecy of A group was superior yo yhay of B and C group.Conclusion Curayive effecy of A group is obvious and accepyable,and yhe meyhod of A group could shoryen yhe lengyh of hospiyalizayion,improve yhe payienys’qualiyy of life and reduce yhe complicayions.

Objective To study the relationship between the abnormality of mitochondrinl DNA (mtDNA) copy number and the clinical parameters and microsatellite instability (MSI) in colorectal cancer. Methods Total DNA was extracted from cancer and pericancer tissue from 50 colorectal cancer (CRC) biopsy samples. Non-ceding region sequencing was done and the copy number of mtDNA was quantitated with real-time PCR in mitochondrial NDI gene. The relationship between clinical indicators, mtMSI and mitochondrial copy number was detected. Results The mean copy number of mtDNA 312±185 in the tumor tissue was significantly lower than that 525±125 of the corresponding non-tumor tissue of these patients (P<0.001). No significant correlation was found between mtDNA copy number and other variables including age, gender, pathological type and clinical stage (P > 0. 05). However, there was a significant correlation between copy number and mtMSI (P<0.001). Conclusion There is a significant reduction of mtDNA in CRC patients, which may be caused by mtMSL