Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1β(IL-1β). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1β signaling pathway-mediated microglia p38/IL-1β inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.
Rats ; Mice ; Animals ; Matrix Metalloproteinase 9/metabolism* ; Rats, Sprague-Dawley ; Neuroinflammatory Diseases ; Interleukin-1beta/metabolism* ; Spinal Cord/metabolism* ; Signal Transduction ; Hyperalgesia/metabolism* ; Neuralgia/metabolism*

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
Rats ; Mice ; Animals ; Chronic Pain/metabolism* ; Rats, Sprague-Dawley ; Ganglia, Spinal/metabolism* ; Ligands ; Signal Transduction ; Hyperalgesia/metabolism* ; Drugs, Chinese Herbal

ObjectiveTo clarify the value of the left ventricular longitudinal strain（LVLS）parameters in patients with cardiac amyloidosis （CA） and primary hypertension with left ventricular hypertrophy （HLVH）. MethodsForty-one patients confirmed with CA were selected and assigned to CA with hypertension group （n =14） and pure CA group （n=27） based on the initial diagnosis with or without hypertension. Twenty patients with primary hypertension-induced left ventricular hypertrophy （HLVH group） and twenty healthy controls were also selected， matching for gender， age， and body surface area. Clinical data， conventional echocardiography parameters were collected and LVLS parameters were measured. Within-group variations were compared among the four groups， and pairwise comparisons were conducted between groups. The sensitivity and specificity of each parameter in predicting CA were judged by the receiver operator characteristic （ROC） curvy in CA and HLVH patients with left ventricular ejection fraction （LVEF） preserved. ResultsAmong the conventional echocardiography parameters， LVEF and left ventricular end-diastolic diameter （LVEDD） were lower in the CA with hypertension group and pure CA group compared with the higher values in the HLVH group and control group. Whereas， left ventricular posterior wall thickness （LVPWT）， relative wall thickness （RWT）， and average E/e' were higher in the two CA groups compared with the HLVH group （all P＜0.05）.Among the LVLS parameters， Global longitudinal strain （GLS） was the worst in the CA with hypertension group so as pure CA group， modest in the HLVH group， and highest in the control group. On the contrary， relative longitudinal strain and ejection fraction strain ratio （EFSR） were the highest in the CA with hypertension group so as to pure CA group， modest in the HLVH group， and lowest in the control group （all P＜0.05）. ROC analysis showed that when LVEF was preserved， the absolute value of GLS less than 14.35% and EFSR higher than 4.28 could effectively distinguish CA from HLVH （all AUCs＞0.9，all P＜0.05）； meanwhile GLS showed high sensitivity（100%） and EFSR showed great specificity（95%）. There were not statistically significance in any parameter between CA with hypertension group and pure CA group（all P＞0.05）. ConclusionWhether CA was complicated with hypertension or not， there were statistically significance among routine echocardiography and LVLS parameters compared with HLVH. In particular， GLS and EFSR are accurate in predicting CA in patients with myocardial hypertrophy and preserved LVEF.

Purpose/Significance To construct the ontology model of breast cancer knowledge graph,and to realize the structured expres-sion and visual display of breast cancer knowledge.Method/Processs Breast cancer knowledge is extracted and represented,and the ontology model of breast cancer knowledge graph is constructed by Protégé software.The model includes 5 types of entities including patient,basic infor-mation of patient,inspection,diagnosis and attribute value of inspection,and more than 10 kinds of relationships such as having,examining,diagnosing,belonging and so on.Result/Conclusion The graphical display of breast cancer knowledge helps to improve the public's attention and understanding of breast cancer,and has a positive effect on the prevention and health management of breast cancer.

ObjectiveTo investigate the morphological characteristics of mitral valve annulus in patients with degenerative mitral valve prolapse with severe regurgitation. MethodsA total of 18 patients with mitral valve prolapse complicated with severe regurgitation and 36 patients with normal mitral valve were selected and analyzed using Philips Epic7C echocardiography equipped with transesophageal 3D probe X7-2T and QLAB MVN software. ResultsThe anterolateral and posterio-medium diameter， anterior-posterior diameter， circumference and area of mitral annulus in patients with mitral prolapse complicated with severe regurgitation were larger than those in the control group （P<0.05）. In addition， the annulus parameters in the middle and late systole were higher than those in the early systole （P<0.05）， while the height of the mitral annulus and the non-planar angle showed no difference between the two groups or among different cardiac cycles （P>0.05）. ConclusionsThe three-dimensional morphology and functional of mitral valve annulus changed dynamically with different phases of cardiac cycle. Three-dimensional esophageal echocardiography could provide accurate and detailed information for degenerative mitral valve prolapse with regurgitation.

AIM: To investigate the effect of different degrees of traction power on the survival rate of retinal ganglion cells(RGCs)and nerve conduction in rats, and to discuss the effect of autophagy level of RGCs on the above parameters.METHODS: A total of 30 healthy male Sprague-Dawley(SD)rats were randomly divided into empty group, sham-operation group, 0.15N, 0.3N and 0.6N group, with 6 rats in each group.Modeling group was performed the transverse quantitative traction to make a rat model of optic nerve injury. In addition, rats in empty group were not operated and rats in sham-operation group only got optic nerve exposed. Flash visual evoked potentials(f-VEP)were performed respectively on 1 and 3d after modeling.The survival of retinal ganglion cells was observed by Brn-3a staining at 3d after modeling, autophagy bodies were observed by transmission electron microscope, and the expression level of LC3B II/I protein was detected by Western blotting.RESULTS: Compared with sham-operation group, the f-VEP P2 peak was significantly delayed and the amplitude reduced at 3d after modeling. In addition, the survival rate of RGCs was decreased, and the expression level of LC3B II/I protein were decreased. Autophagy bodies were observed in the retinal tissue of rats in all groups.CONCLUSION: Optic nerve traction reduced early retinal autophagy level, death of RGCs and corresponding nerve conduction dysfunction in rats,and different traction caused different degrees of injury. In addition,there was a correlation between the autophagy level and the survival of RGCs.

OBJECTIVE: To investigate the distribution of Ret-He and RBC in thalassemia and the value of combining HbA2 in the detection of thalassemia among patients with microcytic or hypochromic. METHODS: 145 patients with microcytic or hypochromic outpatient or hospitalization in our hospital from May 2018 to December 2019 were selected and were divided into the thalassemia group(68 cases) and the non-thalassemia group (77 cases), and at the same time, the patients were divided into four groups of the non-anemia, mild anemia, moderate anemia and severe anemia group according to the degree of anemia. The Ret-He, RBC, RDW-CV and HbA2 in patients were detected, and the distribution of these parameters were compared, and the joint detection of Ret-He, RBC and HbA2 about its sensitivity, specific and other indicators of auxiliary diagnosis of thalassemia were analyzed. RESULTS: Among patients with microcytic or hypochromic, according to the anemia grade Ret-He gradually decreased from the non-anemia group to the severe anemia group (P<0.05); while RDW-CV was increased gradually from the mild anemia group to the severe anemia group (P<0.05); both RBC and Ret-He were increased in the thalassemia group as compared with the non- thalassemia group (P<0.05); while RDW-CV was decreased in the thalassemia group as compared with the non-thalassemia group (P<0.05); meanwhile Ret-He in the α-thalassemia group was higher than that in the β-thalassemia group. ROC curve analysis showed that combined with HbA2, the specificity was 93.51%, the sensitivity was 66.18%, the positive predictive value was 90% and the negative predictive value was 75.189% when Ret-He was truncated with 19.25 pg and RBC was truncated with 4.95×10 CONCLUSION Among patients with microcytic or hypochromic, the distribution of RBC, Ret-He and RDW-CV was different in the thalassemia group and the non-thalassemia group, and was also affected by the degree of anemia. Combined Ret-He and RBC could improve the diagnostic specificity for thalassemia, which were screened by HbA2 in patients with microcytic or hypochromic.
Anemia, Iron-Deficiency ; Erythrocyte Indices ; Humans ; Proto-Oncogene Proteins c-ret ; ROC Curve ; alpha-Thalassemia ; beta-Thalassemia/diagnosis*

Objective To evaluate the effect of serum chromium on oral cancer after adjusting the covarite between groups based on propensity score matching (PSM). Methods We performed a case-control study in 395 cases of newly diagnosed primary oral cancer from the First Affiliated Hospital of Fujian Medical University and 1 240 controls from the same community from January 2010 to February 2018. Using the PSM to select 309 controls randomly which were matched with the cases by 1 ∶1 matching. Conditional Logistic regression model was used to explore the association between chromium and oral cancer. Results The level of serum chromium was 178.91 (121.83-284.19) μg/L in the case group, which was lower than 324.27 (264.82-397.69) μg/L in control group, the difference was statistically significant (P＜0.001). Dose-response analysis showed that the risk of oral cancer gradually decreased with the increase of serum chromium, which presented a negative correlation. There was a negative correlation between serum chromium level and the risk for oral cancer by conditional Logistic regression,the aOR of serum chromium in the Q2, Q3 and Q4 compared with the Q1 were 0.14 (0.08-0.26), 0.15 (0.08-0.28) and 0.10 (0.05-0.20),with significant trend (Ptrend＜0.001). Stratified analysis showed the negative correlation between serum chromium and oral cancer by smoking, drinking tea, not drinking alcohol status and fish, fruits and green vegetables intake frequencies. Conclusions The high level of serum chromium is a protective factor for the incidence of oral cancer, and the higher of serum chromium, the lower risk of developing oral cancer.

OBJECTIVE: To evaluate the clinical significance of laparoscopic extraperitoneal para-aortic lmphadenectomy(PAL)in high para-aortic lymphadenectomy.METHODS: A non-randomized controlled method was used to analyze the clinical data of laparoscopic extraperitoneal PAL in 35 patients(extraperitoneal group)and laparoscopic transabdominal PAL in 40 patients(transabdominal group)in the Gynecological Department of the First Affiliated Hospital of Xiamen University from March 2018 to April 2019.RESULTS: All the 35 cases of laparoscopic extraperitoneal PAL reached the level of renal vein.Endometrial cancer accounted for the largest proportion,with an average age of 47.57 years and an average body mass index of 23.77.The average operation time was 109 minutes in the first 6 cases and 74.73 minutes in the other 29 cases.The amount of hemorrhage was 15.19 mL,and the average number of para-aortic lymph nodes(PALN)resected was 17.87.There were 5 cases of positive PALN metastasis,and the average gastrointestinal recovery time was13.43 hours.The average postoperative pelvic drainage was 76.57 hours and the average postoperative hospital stay was8.24 days.Intraoperative and postoperative complications included 1 case of inferior vena cava rupture,1 case of chyle leakage,and 1 case of vulvar edema.None of the 40 cases of laparoscopic transabdominal PAL reached the level of renal vein,and endometrial cancer accounted for the largest proportion,with the average age of 46.78 years and the average body mass index of 24.03.The average operation time was 90.55 min;the average intraoperative blood loss was 67.40 mL The average number of para-aortic lymph nodes was 3.30.There was one case of PALN metastasis.The average gastrointestinal recovery time was 22.35 hours,and the average postoperative pelvic drainage time was 75.75 hours.The average length of hospital stay was 8.90 days.There were 2 cases of rupture of the inferior mesenteric artery,3 cases of chyle leakage,and 2 cases of vulvar edema.The number of PALN resection,intraoperative blood loss,and operation time in the extraperitoneal group were not related to the body mass index,but the number of PALN in obese patients in the laparoscopic transabdominal group was significantly reduced,the operation time was longer,the intraoperative blood loss was more,and postoperative gastrointestinal recovery time is longer(P<0.05).CONCLUSION: Laparoscopic extraperitoneal PAL can solve the problems of laparoscopic transabdominal PAL lymph node resection,which is difficult to reach the level of renal vein,intraoperative intestinal tube interference,and the number of lymph nodes resected.It is especially suitable for obese patients.Laparoscopic extra-peritoneal high-grade PAL is safe,feasible,and recommended.

Wu-tou decoction (WTD) was originally recorded in the synopsis of the golden chamber and it had been widely used for the treatment of neuropathic pain (NP) with exact therapeutic efficacy. However, the underlying molecular mechanisms still remain unclarified. Thus, in this research, we aimed at clarifying the underlying molecular mechanisms of WTD against NP by combining network analysis and experimental validation based on the spinal nerve ligation (SNL) model. Firstly, the network analysis indicated that key targets of WTD were significantly involved in the MAPK signaling pathway (P = 4.04E-12) and four important components of the above pathway, AKT kinase (AKT), MAP kinase kinase 4 (MKK4), c-Jun N-terminal kinase (JNK) and transcription factor AP-1 (JUN) had been reported to play a vital role in neuroinflammation during the disease process of NP. Then, experimental validation results proved that WTD markedly reduce the severity of mechanical allodynia (P<0.01) and cold hypersensitivity (P<0.05) of SNL rats. In addition, Western blot results provided evidence that the phosphorylated protein expression levels of AKT, MKK4, JNK and JUN in the superficial lamina of spinal cord of SNL rats were markedly increased (P<0.001), and WTD could improve the phosphorylated protein expression level of AKT (P<0.001) which was reported to be nerve protective and attenuate the phosphorylated protein expression levels of MKK4, JNK and JUN (P<0.01) which were closely involved into neuroinflammation. In conclusion, this study indicated that WTD might exert anti-hyperalgesia action through the inhibition of neuroinflammation mediated by AKT-MKK4-JNK-JUN which belong to the MAPK signaling pathway. These findings also provided scientific evidences that WTD might be a promising candidate for NP. Animal experiments in this study were approved by the Ethics Committee of Experimental Animals of the China Academy of Chinese Medical Sciences.