ObjectiveThis paper aims to investigate the mechanism of Jinyang Dingtong plaster in improving the peripheral pain sensitization and synovial fibrosis in rats with knee osteoarthritis （KOA） by blocking the ion channels of transient receptor potentials （TRPs）. MethodsThe active components in the transdermal absorption solution of Jinyang Dingtong plaster were identified by using ultra-high performance liquid chromatography-electrospray ionization-quadrupole ion trap tandem mass spectrometry （UPLC-MS/MS） technology. A KOA rat model was established through intra-articular injection of monoiodoacetic acid. The rats were randomly divided into blank control group， KOA group， compound Nanxing Zhitong plaster Group， and Jinyang Dingtong plaster group， with eight rats per group. Among them， the rats in the compound Nanxing Zhitong plaster group and the Jinyang Dingtong plaster group were intervened with external application treatment. After the intervention period， the cold and mechanical stimulus pain thresholds of rats in each group were detected， and the transverse diameter of the knee joint was measured. The levels of inflammatory factors in the serum such as interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， nerve growth factor （NGF）， and calcitonin gene-related peptide （CGRP） were determined by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of transient receptor potential ankyrin 1 （TRPA1）， transient receptor potential melastatin 8 （TRPM8）， transient receptor potential vanilloid 1 （TRPV1）， transient receptor potential vanilloid 4 （TRPV4）， transforming growth factor-β （TGF-β）， and vascular endothelial growth factor （VEGF） in synovial tissue were detected by Western blot. Histopathological changes in synovial tissue were observed by using hematoxylin and eosin （HE）， Masson， and Sirius red staining， while the expression of type Ⅰ collagen and alpha-smooth muscle actin （α-SMA） was detected by multiplex immunofluorescence. ResultsA total of 35 active components in the transdermal absorption solution of Jinyang Dingtong plaster were identified by UPLC-MS/MS， including phenolic acids， flavonoids， quinones， alkaloids， terpenes， lignans， and coumarins. Among them， the constituents such as berberine， paeoniflorin， ferulic acid， and caffeic acid exhibit clear anti-inflammatory， analgesic， and anti-fibrotic pharmacological effects. Compared to the blank control group， rats in the KOA group showed a significant decrease in cold and mechanical stimuli pain thresholds （P<0.01）. After 14 and 28 days of Jinyang Dingtong plaster intervention， the pain threshold in this group was significantly increased compared to that in KOA group （P<0.01）， showing no significant difference from that in compound Nanxing Analgesic plaster group. Additionally， Jinyang Dingtong plaster reduced the levels of IL-1β， TNF-α， NGF， and CGRP in the serum of KOA rats （P<0.01）， lowered the expression of TRPA1， TRPM8， TRPV1， TRPV4， TGF-β， and VEGF proteins in synovial tissue （P<0.01）， improved synovial pathological damage in KOA rats， and significantly decreased fluorescence intensity of type Ⅰ collagen and α-SMA （P<0.01）. ConclusionJinyang Dingtong plaster can improve the peripheral pain sensitization and synovial fibrosis in KOA rats by downregulating the expression of ion channels of TRPs and related inflammatory and fibrotic factors.

ObjectiveThis paper aims to investigate the mechanism of Jinyang Dingtong plaster in improving the peripheral pain sensitization and synovial fibrosis in rats with knee osteoarthritis （KOA） by blocking the ion channels of transient receptor potentials （TRPs）. MethodsThe active components in the transdermal absorption solution of Jinyang Dingtong plaster were identified by using ultra-high performance liquid chromatography-electrospray ionization-quadrupole ion trap tandem mass spectrometry （UPLC-MS/MS） technology. A KOA rat model was established through intra-articular injection of monoiodoacetic acid. The rats were randomly divided into blank control group， KOA group， compound Nanxing Zhitong plaster Group， and Jinyang Dingtong plaster group， with eight rats per group. Among them， the rats in the compound Nanxing Zhitong plaster group and the Jinyang Dingtong plaster group were intervened with external application treatment. After the intervention period， the cold and mechanical stimulus pain thresholds of rats in each group were detected， and the transverse diameter of the knee joint was measured. The levels of inflammatory factors in the serum such as interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， nerve growth factor （NGF）， and calcitonin gene-related peptide （CGRP） were determined by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of transient receptor potential ankyrin 1 （TRPA1）， transient receptor potential melastatin 8 （TRPM8）， transient receptor potential vanilloid 1 （TRPV1）， transient receptor potential vanilloid 4 （TRPV4）， transforming growth factor-β （TGF-β）， and vascular endothelial growth factor （VEGF） in synovial tissue were detected by Western blot. Histopathological changes in synovial tissue were observed by using hematoxylin and eosin （HE）， Masson， and Sirius red staining， while the expression of type Ⅰ collagen and alpha-smooth muscle actin （α-SMA） was detected by multiplex immunofluorescence. ResultsA total of 35 active components in the transdermal absorption solution of Jinyang Dingtong plaster were identified by UPLC-MS/MS， including phenolic acids， flavonoids， quinones， alkaloids， terpenes， lignans， and coumarins. Among them， the constituents such as berberine， paeoniflorin， ferulic acid， and caffeic acid exhibit clear anti-inflammatory， analgesic， and anti-fibrotic pharmacological effects. Compared to the blank control group， rats in the KOA group showed a significant decrease in cold and mechanical stimuli pain thresholds （P<0.01）. After 14 and 28 days of Jinyang Dingtong plaster intervention， the pain threshold in this group was significantly increased compared to that in KOA group （P<0.01）， showing no significant difference from that in compound Nanxing Analgesic plaster group. Additionally， Jinyang Dingtong plaster reduced the levels of IL-1β， TNF-α， NGF， and CGRP in the serum of KOA rats （P<0.01）， lowered the expression of TRPA1， TRPM8， TRPV1， TRPV4， TGF-β， and VEGF proteins in synovial tissue （P<0.01）， improved synovial pathological damage in KOA rats， and significantly decreased fluorescence intensity of type Ⅰ collagen and α-SMA （P<0.01）. ConclusionJinyang Dingtong plaster can improve the peripheral pain sensitization and synovial fibrosis in KOA rats by downregulating the expression of ion channels of TRPs and related inflammatory and fibrotic factors.

Objective To explore the optimal ratio of Baitong decoction based on efficacy,clarify its spectrum-effect relationship,and identify its potential quality markers.Methods An ulcerative colitis(UC)model in mice was established using dextran sulfate sodium.The efficacy of Baitong decoction with varying drug ratios was assessed by evaluating the apparent score,pathological score and inflammatory factor changes of UC in each group of experimental animals.The fingerprints of Baitong decoction with different ratios were established by high performance liquid chromatography(HPLC),and the relationship between the content of each substance and its efficacy was analyzed by partial least squares regression to determine the potential quality markers of Baitong decoction.Results Baitong decoction was most effective in relieving ulcerative colitis when the mass ratio of Fuzi,Ganjiang and Congbai was 1∶2∶2.The fingerprinting identified 14 common peaks across 7 ratios,with 9 peaks were found to be associated with the remission of ulcerative colitis by partial least squares regression analysis.Conclusion The optimal ratio of Fuzi,Ganjiang and Congbai for treating UC is 1∶2∶2.The spectrum-effect relationship analysis suggested that the quality markers of Baitong decoction may be the substances represented by peak 2(benzoylaconine),3,5,6,8(mesaconine),9(aconitine),10(hypaconitine),13(10-gingerol)and 14.

Objective To study the effects of different implantation angles of bi-leaflet mechanical heart valve(BMHV)on swirling flow in the aorta.Methods Based on the aortic CT images of a healthy volunteer,the effects of 4 different valve implantation angles(0°,45°,90° and 135°)on the aortic swirling flow under constant flow conditions were studied by computational simulation.Results The implantation of BMHV could seriously interfere with the aortic swirling flow,affecting the structure and helicity distributions of the swirling flow in ascending aorta,thus resulting in disturbed blood flows distal to the valve.The 135° implantation angle caused the most disruption to the swirling flow,leading to the largest areas of reversed swirling flows,while the 0° and 45° implantation angles caused relatively smaller damage to the swirling flow.The areas with low wall shear stress(<0.5 Pa)were the smallest when the implantation angle of BMHV was 0°.Conclusions At the implantation angle of 0°-45°,the disruption of BMHV to the swirling flow in ascending aorta was relatively small.Therefore,for different patients,the selection of implantation angle should be individualized according to the spatial geometry of their aorta(including the aortic sinuses),and the implantation angle can be determined between 0°-45°.

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*

Objective:To explore the clinical value of aspirin combined with atorvastatin in the prevention of new onset atrial fibrillation after off-pump coronary artery bypass grafting (OPCABG).Methods:208 patients with coronary artery bypass grafting in our hospital from June 2019 to June 2021 were selected as the research subjects and divided by a random number table method into groups. The control group (104 cases) was treated with aspirin before operation, and the observation group (104 cases) was treated with aspirin and atorvastatin before operation. ECG monitoring was carried out continuously for 7 days of patients in the two groups, and the occurrence and duration of AF were recorded. The clinical therapeutic efficacy, incidence and adverse reactions of AF, left atrial diameter and high-sensitivity C-reactive protein (hs-CRP) level were observed before and after treatment.Results:The incidence of AF in the observation group was significantly lower than that in the control group, the difference was statistically significant ( P<0.05). There was no statistical significant difference in the starting time of AF between the two groups after operation ( P>0.05). The duration of AF in the observation group was better than that in the control group, the difference was statistically significant ( P<0.05). Before treatment, there was no statistical significant difference in left atrial diameter and hs-CRP level between the two groups ( P>0.05). After treatment, the left atrial diameter in the observation group returned to that before treatment, and there was no statistical significant difference in the same group ( P>0.05). The left atrial diameter in the control group was higher than that before treatment, and there was statistical significant difference in the same group ( P<0.05). The level of hs-CRP was lower than that in the control group, the difference was statistically significant ( P<0.05). There were no adverse reactions in both groups. Conclusion:Aspirin combined with atorvastatin has a significant effect in preventing new onset AF after OPCABG. It can reduce the incidence of postoperative AF, shorten the duration of AF, effectively control the inner diameter of left atrium, reduce the degree of postoperative inflammatory reaction, and has no adverse effects. It is worthy of clinical application.

With the appearance of the disadvantages of traditional tumor treatment, immunotherapy has entered people′s horizons as modern emerging treatment strategies, among which plant polysaccharides have received much more attention due to their antitumor activity and significant immunomodulatory effects. Tumor-associated macrophages (TAMs), as a component of tumor microenvironment, are important factors affecting tumors, and the regulation of TAMs by plant polysaccharides is one of the effective immunotherapy to treat tumor. In this review, we mainly described the regulation of TAMs by plant polysaccharides and the underlying mechanisms, and then gave an outlook on the research interests and the development of plant polysaccharides as immune adjuvants, aiming to provide reference for the study of plant polysaccharides in the immunotherapy for tumors.

Objective:To explore the role of genetic testing of VKORC1 and CYP2C9 in determining the dosage of warfarin after aortic valve replacement.Methods:A total of 172 patients receiving warfarin after aortic valve replacement were divided into a control group(86 cases) and an experimental(86 cases) group based on acceptance of genetic testing. In the experimental group, three loci of VKORC1 and CYP2C9 were tested by polymerase chain reaction-restriction fragment length polymorphism technique, and the initial dose of warfarin was determined based on the genetic testing results and warfarin oral-dose table recommended by U. S. Food and Drug Administration(FDA). In the control group, warfarin(3 mg/d) was used as the initial dose. The international normalized ratio(INR) of each patient was continuously monitored after medication. The percentages of patients meeting the target INR in the two groups at specific time points and at 3-month follow-up after discharge from the hospital were monitored, and the incidence of various adverse events was compared between the groups.Results:Based on the results of genetic testing, 68 patients received 3 mg/d(79.1%), 10 patients received 1.5 mg/d(11.6%), and eight patients received 6 mg/d(9.3%) as the initial dosages of warfarin in the experimental group. The percentages of the patients meeting the target INR on the third and sixth day of postoperative medication were 45.3% and 73.3%, respectively, in the experimental group, and 29.8% and 58.3%, respectively, in the control group( P<0.05). The INR critical values during hospitalization occurred in 2.3% in the experimental group and in 7.1% in the control group, while the percentage of the patients meeting the target INR after 3 months was 86.1% in the experimental group and 83.1% in the control group. Conclusion:Genetic testing may guide the selection of the initial dose of warfarin after heart valve replacement to rapidly achieve a stable dose.

Parkinson′s disease is a neurodegenerative disease characterized by bradykinesia, resting tremor, and hypermyotonia. Its pathological features are the loss of nigra dopamine neurons and the abnormal aggregation of α-synuclein, and there is currently no treatment that blocks the progression of the disease. Gene therapy, by increasing the expression of neurotrophic factors and increasing levels of neurotransmitters, may slow, terminate, or even reverse the progression of the disease, so it gets more attention. This article reviews the progress of registered clinical research on gene therapy for Parkinson′s disease.

Objective:To explore the outcomes and mechanisms of coronary endarterectomy combined with electrocautery in patients with diffused coronary artery disease undergoing coronary artery bypass grafting (CABG).Methods:From January 2017 to September 2018, 300 patients undergoing CABG with left anterior descending artery endarterectomy were randomly divided into two groups, after fully informed the risks and other related issues regarding the operations. All the patients in the two groups were treated with CABG. In the study group, patients underwent electrocautery immediately after endarterectomy, whereas in the control group, patients underwent endarterectomy only. The electrocardiogram and serological examination (TNI, IL-6 and TNF-a) were performed at 2 h, 24 h, 72 h and 120 h after operation. The follow-up duration was 1 year.Results:Nine patients in the study group, and 25 patients in the control group had ST segment elevation. The levels of TNI, IL-6 and TNF-a were continuously increased in both groups, and reached the peak at 24 h, then decreased slowly. The levels of TNF-a were significantly lower at 2 h postoperatively in the study group ( P=0.01). There was no significant difference in the levels of TNI and IL-6 between the two groups. The levels of TNI, TNF-a and IL-6 were significantly lower in the electrocautery group at 24 h, 72 h, and 120 h after operation( P<0.05). One year after operation, incidences of ST segment elevation in the study group were significantly lower than that in the control group, and there was no significant difference in restenosis rate and myocardial infarction rate. Conclusion:Endarterectomy combined with electrocautery may prevent the restenosis of the lumen and blood turbulence, smooth the inner wall of the vessel, slow down the release of inflammatory factors in the peripheral blood, inhibit the expression of inflammatory factors in the vessels, and reduce the myocardial damage. The short-term effect was satisfactory; the long-term anti-inflammatory and antithrombotic effect still need further investigations.