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 expression and diagnostic value of circulating microRNA(miR)-126-3p in non-small cell lung cancer(NSCLC).Methods Multi-centred miR chips and sequencing data were col-lected to investigate the differential expression of circulating miR-126-3p in NSCLC.In order to evaluate the comprehensive expression level of circulating miR-126-3p in the cycle,the standardized mean difference(SMD)and summary receiver operating characteristic(sROC)curve were calculated,and the area under curve(AUC)of sROC curve was analyzed.Sensitivity,specificity,positive negative likelihood ratio were ex-plored,and the expression of circulating miR-126-3p was further comprehensively analyzed in combination with tissue.By using miRDB,starBase v2.0,and TargetScan 7.1,combined with up-regulated differentially expressed genes in NSCLC,potential target genes of circulating miR-126-3p were screened using complemen-tary sequence method.Results Based on six circulating miR datasets,the expression level of circulating miR-126-3p was higher than that of the control group,and the difference was statistically significant(P＜0.05).The receiver operating characteristic curves showed that circulating miR-126-3p had strong diagnostic efficacy(AUC＞0.5),and the comprehensive expression of circulating miR-126-3p was lower in 199 cases of NSCLC group than in the control group(SMD=-1.46).The sROC curve showed that circulating miR-126-3p distin-guished the NSCLC group from the control group with high accuracy(AUC=0.91),Egger's test showed no publication bias(P＞0.05),with sensitivity and specificity 0.80,and positive likelihood ratio and negative likelihood ratio were 5.37 and 0.18,respectively.In addition,a comprehensive analysis of the circulation and tissue of 1 320 NSCLC samples from 26 datasets showed that circulating miR-126-3p expression was lower in NSCLC group than in the control group(SMD=-2.07).The sROC curve showed that low-expression circu-lating miR-126-3p had high accuracy in distinguishing between the NSCLC group and the control group(AUC=0.97).In addition,potential target genes ADAM9 and SLC7A5 were screened for circulating miR-126-3p,and their expression in NSCLC group was higher than that in the control group.Conclusion Low ex-pression of circulating miR-126-3p in the circulation may be an important biomarker for high-precision screen-ing of NSCLC.

Objective:To explore the application value of whole-process ultrasound-guided percutaneous portal vein puncture islet transplantation.Methods:From October 2018 to May 2021, 16 diabetics underwent whole-process ultrasound-guided percutaneous portal vein puncture islet transplantation at First Affiliated Hospital of Sun Yat-sen University.The whole process was guided by ultrasound for completing percutaneous portal vein puncture catheterization, islet infusion monitoring, bleeding prevention and ablation hemostasis after bleeding.Results:Ten patients [8 males and 2 females with a mean age of(45.9±21.1)years]underwent 16 islet transplants, including one islet(5 cases), two islets(4 cases)and three islets(1 case). A single puncture was successfully performed without damage to other extrahepatic organs, persistent portal hypertension, portal vein embolism or infection.Bleeding at liver puncture site occurred in 3 cases and ultrasound radiofrequency ablation was performed for immediate hemostasis.Among them, postoperative blood glucose stabilized at 4~12 mmol/l post-operation.And 5 cases(31.3%)achieved insulin independence for>2 months and 10 cases(62.5%)lowered insulin dosage by>50% as compared with preoperative level.The level of fasting C-peptide recovered or was higher than normal in 10 cases(62.5%)and became obviously elevated in the remainders.In 11 cases(68.8%)of them, liver transaminase was briefly and mildly elevated post-operation, and no other complications were observed.Conclusions:The whole-process ultrasound-guided percutaneous portal vein islet transplantation is both safe and feseasible.It avoids the injury of transplanted kidney caused by contrast agent and radiological radiation to operator and patient.It is a method of islet transplantation worth a wider popularization.

Adaptation, Physiological ; Adenosine Monophosphate ; administration & dosage ; analogs & derivatives ; pharmacology ; therapeutic use ; Administration, Intranasal ; Alanine ; administration & dosage ; analogs & derivatives ; pharmacology ; therapeutic use ; Animals ; Betacoronavirus ; genetics ; physiology ; Chlorocebus aethiops ; Coronavirus Infections ; drug therapy ; virology ; Disease Models, Animal ; Female ; Host Specificity ; genetics ; Lung ; pathology ; virology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mutation, Missense ; Nasal Mucosa ; virology ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; RNA, Viral ; administration & dosage ; genetics ; Turbinates ; virology ; Vero Cells ; Viral Load ; Virus Replication

Objective: To evaluate the efficacy and safety of laparoscopic surgery in the treatment of gallstones and common bile duct stones. Methods: Eighty-seven patients with gallstones complicated with common bile duct stones who underwent concurrent laparoscopic surgery at Zhoushan Hospital from December 2015 to December 2017 were enrolled.The patients were divided into A group and B group according to the digital table.A group(38 cases) underwent laparoscopic cholecystectomy (LC) combined with laparoscopic common bile duct exploration (LCBDE), and B group(49 cases) underwent endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST) combined with laparoscopic cholecystectomy (LC). The curative effect of the two groups was observed.The operation time, the success rate of the operation and the rate of laparotomy were recorded in the two groups.The corresponding hospitalization time and cost were compared.The safety of the two different procedures was compared after surgery, and the complications of the two groups were recorded. Results: In A group, the average diameter of common bile duct stones was (1.02±0.25)cm, the average diameter of common bile duct diameter was (1.15±0.25)cm.In B group, the mean diameter of common bile duct stones was (0.99±0.26)cm, and the average diameter of common bile duct was (1.13±0.26) cm.The differences between the two groups were not statistically significant (t=0.513, 0.437, 0.367, P=2.083, 1.533, 1.095). The successful operation rate of A group was 92.11%(35/38), which in B group was 91.84%(45/49), the difference was not statistically significant between the two groups(χ²=0.006, P=0.974). The incidence rate of complications in B group was 20.41%, which was significantly higher than that in A group, the difference was statistically significant(χ²=3.654, P=0.019). The hospitalization time, hospitalization expenses in A group were (10.6±2.6)d, (26 649.8±3 478.6)CNY, respectively, which were significantly better than those in B group (t=21.971, 17.168, all P<0.05). Conclusion The efficacy of LC combined with LCBDE for patients with gallstones complicated with common bile duct stones is better than ERCP/EST combined with LC surgery, and the safety of the former is higher than the latter.

Objective: Screen the pathogenic genes of a pedigree with clinical manifestation of familial dilated cardiomyopathy in Inner Mongolia. Methods: A total of 3 patients with dilated cardiomyopathy and 20 family members from the same family were examined in Ordos Central Hospital in Inner Mongolia from October, 2003 to August, 2017. Data on medical history, physical examinations, electrocardiograms, and echocardiography were obtained. 5 ml peripheral blood was sampled for per person. Chip Capture Sequencing technology was used to capture all the exons and splice sites of the genes that associated with hereditary cardiomyopathy and hereditary arrhythmia. The mutations in these genes were detected by high-throughput sequencing. All suspected pathogenic loci identified by high-throughput sequencing were verified by Sanger sequencing used for mutation detection. One hundred and fifty gender, age and race matched healthy people were included as the control group. Results: Pathogenic gene variations were detected in 3 symptomatic family members and 1 carrier from the pedigree. Five pathogenic gene variations were identified in the proband (Ⅱ1), a pSer236Gly and a pArg215Cys variation in the MYBPC3 gene, a pGln90Arg variation in the DSP gene, and pAsn2912Asp and pGlu2910Val variation in the DMD gene. One pathogenic variation was detected in Ⅲ3, which was a pArg215Cys variation in the MYBPC3 gene. Two pathogenic variations were detected in Ⅲ7, a pSer236Gly variation in the MYBPC3 gene and a pGln90Arg variation in the DSP gene. Two pathogenic variations were detected in the Ⅳ7, a pSer236Gly variation in the MYBPC3 gene and a pGln90Arg variation in the DSP gene. No gene variation loci were detected in the other family members and the control group. Conclusion MYBPC3 gene, DSP gene and DMD gene variations are present in the familial dilated cardiomyopathy pedigree from Inner Mongolia, and these variations may be related with familial dilated cardiomyopathy.

Multiple sclerosis(MS)is a demyelinating disease of the central nervous system and one of the most common autoimmune diseases,characterized by wide-spread lesions and relapsing-remitting encephalomyelitis,accompanied by optic nerve damage.Patients worldwide total about 2.5 million,mostly young adults and women.This disease remains incurable. Dimethylfumarate (DMF)is a new oral drug for MS,which was approved by the FDA in 2013 for clinical treatment of re-lapsing-remitting MS.It can reduce the activity of disease,and the relapsing-remitting MS relapse.This paper outlines the application of DMF to the treatment of MS and its mechanism of action.

ObjectiveTo observe in vivo segmental lumbar motion in patients with lumbar disc herniation (LDH) during functional weight-bearing activities.MethodsFifteen patients with LDH at L4-5 were studied as experimental group.Ten healthy volunteers were recruited as control group.Three-dimension(3D) lumbar spine models of L3,L4 and L5 were reconstructed from thin section CT scans.Spine motions were then reproduced by matching lumbar spine models and images got from dual fluoroscopic imaging system (DFIS)under different motion state (standing,flexion-extension,left-right twisting and left-right bending).From local coordinate systems at the end plates,the motion of the cephalad vertebrae relative to the caudal vertebrae was calculated for vertebrae levels:L4-5 and L3-4.ResultsThe motion pattern at L4-5 was found to be altered.During flexion-extension,the migrations of the affected segments along the frontal axis,sagittal axis,vertical axis were similar with that of the control group,but the rotation angle along the frontal axis was significantly larger than that of the control group (P＜0.05).During left-right bending and left-right twisting,the migration and rotation angle along the frontal axis were significantly larger than those of control group.During flexionextension,the migrations of the neighboring segments (L3-4) along the three axes were larger than those of the control group,but there were no statistical significances.During left-right bending and left-right twisting,the migrations of the neighboring segments (L3-4) along the vertical axis were significantly larger than those of the control group (P＜0.05).ConclusionThe 3D lumbar motion pattern in LDH patient is different with that of normal people.For the affected segment,compared with the normal people,the range of flexion-extension motion and the translocation in left-right direction were significantly larger,but the rotation range along the vertical axis was smaller.