1.Development of analgesic drugs targeting Nav1.7: advances in clinical trials and discovery of selective inhibitors
Rui HAN ; Yi-lin CAI ; Xiao-tong ZHENG ; Fan-qi LIN ; Fan ZHANG
Acta Pharmaceutica Sinica 2024;59(9):2417-2428
The voltage-gated sodium channel subtype Nav1.7 is highly expressed in nociceptive sensory neurons and is a key pathogenic target in several human hereditary pain syndromes. In recent years, a large number of studies have shown that Nav1.7 plays an important role in inflammatory, neuropathic, and nociceptive pain. Therefore, targeting Nav1.7 is a new strategy and hotspot for the development of novel analgesics. This review introduces the structure and function of Nav1.7, its regulatory role in pain, highlights the development progress of small-molecule Nav1.7 inhibitors in clinical trials, and analyzes the preclinical development of highly specific Nav1.7 inhibitors, with a view to providing reference for the development of Nav1.7 analgesic drugs.
2.Current situation analysis of blood pressure and blood lipids in overweight and obese population from coastal areas of Fujian province
Huirong LIN ; Pengli ZHU ; Huazhen XIAO ; Xinnuan WEI ; Fan LIN ; Feng HUANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2016;25(1):6-11
Objective:To investigate current situation of overweight and obesity among population from coastal areas of Fujian province ,and study their correlation with blood pressure (BP) and blood lipids . Methods :A total of 3343≥30 years people from coastal areas of Fujian province were enrolled using cross -sectional survey .Body height and mass ,BP ,waist circumference (WC) ,blood glucose and blood lipids etc .were measured .The correlation among BP ,blood lipids and BMI were statistically analyzed . Results:Detection rates of overweight and obesity were 34.6% and 10.0% respectively .Overweight rate of men was significantly higher than that of women (40.4% vs . 30.7% , P<0.05);percentages of overweight and obese population gradually rose along with age increased before 70 years ,and it showed declining trend after 70 years .Compared with normal weight people of corresponding age , BP and WC significantly rose in overweight and obese young people (<40 years) , P<0.01 all;there were signifi‐cant rise in BP ,WC ,TC and LDL‐C levels ,and significant reduction in HDL‐C level in overweight and obese mid‐dle-aged and aged people (>40 years) , P<0.05 or <0.01. Partial correlation analysis indicated that BMI was positively correlated with WC ,SBP ,DBP ,TC ,LDL‐C and HbA1c levels ( r=0.701 ,0.218 ,0.238 ,0.068 ,0.120 , 0.135 ,P<0.01 all) ,and inversely correlated with TG and HDL‐C levels (r= -0.069 both ,P<0.01 both) .Mul‐tifactor linear regression analysis indicated that BMI was significantly correlated with WC ,sex ,age ,DBP ,HDL‐C and FBG levels .After controlling age ,sex and blood glucose etc .,binary Logistic regression analysis indicated that overweight (OR=2.283 ,95% CI 1.915~2.721) and obesity (OR=4.419 ,95% CI 3.329~5.865) were risk fac‐tors for hypertension and dyslipidemia [overweight (OR= 1.356 ,95% CI 1.160~ 1.584) ,obesity (OR= 1.691 , 95% CI 1.319~2.167 )] , P<0.01 all .Conclusion:Prevalence rates of overweight and obesity are high in coastal population in Fujian province .Percentages of hypertension ,dyslipidemia ,DM and cardiovascular risk factor aggre‐gation significantly rise among overweight and obese people ,so controlling body mass is of important significance for prevention and treatment of chronic diseases ,including hypertension ,DM and dyslipidemia etc .
3.Network pharmacology study of mechanism on xuesaitong injection against retinal vein occlusion.
Lin-Li WANG ; Xiao-Ping ZHAO ; Zhuan-You ZHAO ; Xiao-Hui FAN ; Zheng LI
China Journal of Chinese Materia Medica 2014;39(12):2322-2325
Retinal vein occlusion (RVO) is a common clinical disease causing vision loss. Risk factors such as diabetes, atherosclerosis are closely associated with RVO. Xuesaitong injection is used extensively in clinical treatment of RVO, however the mechanism is still unclear. In this study, we investigated the protective effect of Xuesaitong injection on RVO rat model. Using a compound-target network of Xuesaitong on anti-RVO constructed by literature mining, we aim to elucidate the multi-compound, multi-target effect of Xuesaitong injection. Fifteen potential targets of Xuesaitong injection associated with inflammation, angiogenesis, apoptosis, and coagulation were identified in this study. VEGF, IL-1beta and IL-6, three important targets in the compound-target network were further experimentally validated. This study provided experimental evidence for Xuesaitong injection being effective in treating RVO and a network view on its anti-RVO mode of action through a multi-compound and multiple-target mechanism.
Animals
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Drugs, Chinese Herbal
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administration & dosage
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Gene Regulatory Networks
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drug effects
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Humans
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Interleukin-6
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genetics
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metabolism
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Male
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Rats
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Rats, Sprague-Dawley
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Retinal Vein Occlusion
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drug therapy
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genetics
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metabolism
4.Multicentral randomized controlled study on acupuncture at Sifeng (EX-UE 10) for treatment of infantile malnutrition.
Fan-rong LIANG ; Xiao-hong XIA ; Xiao-hong PENG ; Xiu-li YUAN ; Lin-bo XU ; Xiao-fan LIU
Chinese Acupuncture & Moxibustion 2006;26(1):3-7
OBJECTIVETo evaluate therapeutic effect of acupuncture at Sifeng (EX-UE 10) on infantile malnutrition.
METHODSMulticentral, randomized, controlled and single blind test was adopted. 222 infants of malnutrition were divided into an acupuncture group (n=110) and a medicine group (n=112). The acupuncture group were treated with acupuncture at bilateral Sifeng (EX-UE 10), once each week, for 4 times; and the medicine group were treated with oral administration of Yiqi Jianpi Oral Liquid, twice each day, one ample each time, for 4 weeks. The therapeutic effect was evaluated by improvement of symptoms and signs in the syndrome cumulative score scale, and changes of serum insulin-like growth factor-I (IGF-I), pre-albumin (PA), hemoglobin and red-cell count.
RESULTSTwo hundred and twenty-two cases were enrolled in the 4 centers and 212 cases completed the test. The acupuncture group in improvement of appetite, body weight, subcutaneous fat thickness of the abdomen, etc. were superior to the medicine group (P < 0.01), but there was no significant difference between the two groups in improvement of the body height. There was no significant increase of serum IGF-I level in the two groups, and the acupuncture group in increase of PA was superior to the medicine group (P < 0.05). After treatment, hemoglobin and red-cell count increased significantly in the treatment group (P < 0.01), and hemoglobin increased significantly in the medicine group.
CONCLUSIONAcupuncture at Sifeng (EX-UE 10) has obvious therapeutic effect on infantile malnutrition.
Acupuncture Points ; Acupuncture Therapy ; Appetite ; Humans ; Infant Nutrition Disorders ; Single-Blind Method ; Treatment Outcome
5.Effect evaluation of supplementary food nutrition package for infants aged 6-24 months in rural areas of Hainan
WU Gui-hua ; FAN Li-chun ; HUANG Yan ; DOU Qian-ru ; WU Shao-jing ; FAN Xiao-lin ; CAO Xia
China Tropical Medicine 2022;22(09):837-
Abstract: Objective To analyze the effect of nutrition package on the nutritional status and prevalence of children in rural areas of Hainan Province, and provide scientific basis and suggestions for further improving the nutritional and health status of children in this region. Methods Four cities and counties were randomly selected as the intervention group, and four cities and counties matched with the intervention group in terms of population, economy, social culture, maternal and child health work foundation of township health centers, physical nutrition and health status were selected as the control group.With the combination of monitoring and prospective cohort study, infants in the intervention group and the control group were studied from June 1, 2020, and they were intervened for 12 months with supplementary food nutrition package. Before and after intervention, the nutrition and health status of infants aged 6-24 months in the intervention group and the control group were investigated to evaluate the nutritional and health effects of supplementary food nutrition package for infants aged 6-24 months in rural Hainan Province. Results A total of 999 infants were investigated, including 427 in the intervention group and 572 in the control group. After 12 months of nutritional intervention, there was no significant difference in weight-for-age Z-score (WAZ) and height-for-age Z-score (HAZ) and weight-for-height Z-score (WHZ) between the intervention group and the control group (P>0.05). The rate of emaciation of the intervention group was 1.64%, which was significantly lower than 3.67% of the control group (P<0.05). There were no significant differences in the rate of growth retardation (2.81% and 3.32%, respectively) and underweight (0.47% and 1.92%, respectively) between the intervention group and the control group (P>0.05). The rate of respiratory infection and diarrhea in the intervention group were 9.13% and 1.17%, which were significantly lower than corresponding 23.25% and 3.15% in the control group (P<0.05). The hemoglobin of the intervention group and the control group were 117.24 g/L and 114.51 g/L respectively, and the rates of anemia were 11.11% and 22.84% respectively, the differences were statistically significant (P<0.05). Conclusions The intervention of nutrition package in rural areas of Hainan Province has achieved the expected results, and supplementary food nutrition package has reduced the incidence of malnutrition and respiratory infection and diarrhea in recent two weeks in infants and anemia to a certain extent. We should attach great importance to the supplementary nutrition package for right-age children and promote the growth and health of children in rural areas through supplementary nutrition package, and continuously improve the nutrition and health level of children in Hainan Province.
6.Diagnostic value of FDG-PET in the detection of bone marrow involvement in patients with diffuse large B-cell lymphoma.
Xu ZHANG ; Wei FAN ; Xiao-Ping LIN
Chinese Journal of Hematology 2008;29(12):832-835
OBJECTIVETo evaluate the diagnostic value of bone marrow (BM) involvement detected by F-18-fluorodeoxyglucose-positron emission tomography/computed tomography ((18)F-FDG PET/CT) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).
METHODSThe study population comprised 81 consecutive patients with newly diagnosed DLBCL. All patients had both (18)F-FDG PET/CT and standard BM biopsy at iliac crest. In 9 patients, additional direct BM biopsy at FDG-avid bone lesion was performed.
RESULTSAmong all 81 cases, 23 were diagnosed as BM involvement by PET/CT. Of the 23 positive cases 17 were confirmed by biopsy. However, only 11 cases were diagnosed by merely bilateral iliac crest biopsy. In patients in early stage of disease (18)F-FDG PET/CT had the same results as bilateral iliac crest biopsy.
CONCLUSION(18)F-FDG PET/CT is superior to standard BM biopsy in detecting BM involvement in newly diagnosed DLBCL patients. In patients with FDG-avid bone lesions, direct PET/CT-guided bone biopsy seems to be more accurate than standard BM biopsy.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Marrow ; pathology ; Female ; Fluorodeoxyglucose F18 ; Humans ; Leukemic Infiltration ; diagnostic imaging ; Lymphoma, Large B-Cell, Diffuse ; diagnostic imaging ; pathology ; Male ; Middle Aged ; Positron-Emission Tomography ; methods ; Young Adult
7.Botulinum toxin injection can reduce arthritis pain by inhibiting the expression of calcitonin gene-related peptide in the dorsal root ganglia
Chenglei FAN ; Xiao CHU ; Kaile WANG ; Lin WANG ; Zhenyuan NIU ; Tieshan LI
Chinese Journal of Physical Medicine and Rehabilitation 2016;38(9):652-658
Objective To explore the analgesic effect of intra-articular botulinum neurotoxin type A (BoNTA) injection in rats with adjuvant-arthritis pain,to quantify the expression of calcitonin gene-related peptide (CGRP) in the dorsal root ganglia (DRG) associated with arthritis pain,and to investigate the retrograde axonal transport of BoNT-A into the DRG after peripheral injection.Methods Ninety Sprague-Dawley rats were randomly divided into groups A,B,C,D and E,each of 18.A murine model of adjuvant-arthritis pain was established by injecting 50 μL of complete Freund's adjuvant into the left ankle in all the mice except those in group A.The control group A was treated with intra-articular injection of 50 μL of saline solution.Three weeks later,groups A and B were treated with a 20 μL intra-articular saline injection,while groups C,D and E received an intra-articular injection of BoNT-A at 1 U/20 μL,3 U/20 μL or 10 U/20 μL respectively.Pain threshold and muscle strength were graded before and 1,5,15 and 21 days after the modelling,as well as at 1,3,5 and 14 days after the BoNT-A treatments.Protein expression and the CGRP-positive cell number were observed,as well as any BoNT-A-cleaved synaptosomal-associated 25 kDa protein (cl-SNAP-25) in the DRG using Western blotting and immunofluorescence.Results Compared with group A,there was a significant decrease in the average mechanical withdrawal threshold and muscle strength and a significant increase in the protein expression and the CGRP-positive cell number in the other 4 groups.Compared with group B,the mechanical withdrawal threshold had increased significantly more in groups D and E at 5 days after the BoNT-A injection and in group C at 14 days after the treatment.Compared with group B,the protein expression and the number of CGRP-positive cells were significantly lower in groups D and E at 3 days after the BoNT-A injection.The decrease in group C was significant after 14 days.No significant differences were found between groups D and E in any measurement at any time point.There was no significant difference among groups B,C and D in terms of muscle strength.Five days after the BoNT-A injection,significantly decreased muscle strength was observed in group E.In addition,BoNT-A cleaved-SNAP-25 was detected in the DRG.Conclusion BoNT-A can reduce arthritis pain through inhibiting the expression of CGRP in the DRG.Its analgesic effect has a dose response.A peripheral injection of BoNT-A can arrive at the DRG through retrograde axonal transport.
8.Pathological morphology of vascular endothelial injury and arteriosclerosis caused by high fluoride and the effects of selenium
Jian-chao, BIAN ; Xiao-xia, YANG ; Xin-ying, LIN ; Qiu-li, ZHU ; Ting, FAN
Chinese Journal of Endemiology 2010;29(6):593-598
Objective To study morphological changes of rabbit artery endothelial cell injury and atherosclerosis caused by high fluoride and the role of selenium. Methods Twenty healthy male New Zealand white rabbits, body weight (2.0 ± 0.5)kg, were randomly divided into control group(drinking deionized water, fed basic diet), fluoride group(drinking fluoride 100 mg/L deionized water, fed basic diet), selenium group(drinking selenium 1 mg/L deionized water, fed basic diet), fluoride plus selenium group(drinking fluoride 100 mg/L deionized water, selenium 1 mg/L of deionized water, fed basic diet). The experimental period was 6 months. At 0, 3, 6 months of the experiment, serum fluorine and selenium levels were determined. At the end of the experiment,thoracic aorta was collected to observe its pathology and ultrastructural changes. Results Serum fluoride was significantly higher at the 3rd and the 6th month of experiment(all P < 0.01 ) in fluoride group[ (0.589 ± 0.146),(0.772 ± 0.175)mg/L] and fluoride plus selenium group[ (0.502 ± 0.094), (0.693 ± 0.158)mg/L] than in control group[ (0.174 ± 0.002), (0.208 ± 0.031 )mg/L] and serum fluoride was significantly higher at 6 months than at 3 months(P < 0.05 ) in fluoride group. Serum selenium was significantly higher at the 3rd and the 6th month of experiment (all P < 0.01 ) in selenium group[ (0.252 ± 0.022), (0.319 ± 0.052)mg/L] and fluoride plus selenium group[ (0.239 ±0.016), (0.294 ± 0.018)mg/L] than in control group[(0.135 ± 0.014), (0.167 ± 0.019)mg/L], and serum selenium was significantly higher at the 6th month than at 3rd month of experiment in selenium group(P < 0.05). Endothelial cell apoptosis indices were (4.92 ± 1.32)%, (30.30 ± 6.80)%, (6.57 ± 2.14)% and (14.29 ± 2.99)%, respectively in control group, fluoride group, selenium group and fluoride plus selenium group. Their main effect of fluorine and selenium was statistically significant (F = 106.833,20.082, all P < 0.01 ). There were antagonistic effect between fluoride and selenium(F = 30.402, P < 0.01 ). Pathological changes of rabbit aortic endothelial cells in fluoride group included endothelial with attached fibrin and red blood cells, and structural of the cells changed, with serious vascular injury; in fluoride plus selenium group apoptosis of endothelial cells decreased, with reduced number of attached red blood cells and fibrin, endothelial cell structure normal, the extent and scope of vascular damage significantly reduced. Conclusions Appropriate amount of selenium inhibits the apoptosis of endothelial cells induced by high fluoride, reduces aortic structural damage caused by high fluoride, and maintains the integrity of endothelial cells, thereby antagonizes the vascular damage and atherosclerosis induced by high fluoride.
9.Clinical impact of 18F-FDG PET/CT on suspected cervical cancer recurrence
Ying-ying, HU ; Xu, ZHANG ; Wei, FAN ; Xiao-ping, LIN ; Pei-yan, LIANG ; Xin-ru, SUN
Chinese Journal of Nuclear Medicine 2011;31(2):73-76
Objective To evaluate the clinical impact of 18F-FDG PET/CT on patients with suspected cervical cancer recurrence. Methods Fifty-one cervical cancer patients, clinically suspected to have tumor recurrence during follow-up, underwent 18F-FDG PET/CT examination. 18 F-FDG PET/CT results were compared with those of conventional images, as referred to histopathology or clinical follow-up. Impacts of 18F-FDG PET/CT were evaluated based on documented changes of clinical management. Results In total, 43 patients were found to have positive lesions by 18F-FDG PET/CT, in which 40 were true recurrence,but 2 were pelvic abscess and 1 was radiation enterocolitis. Other 8 patients were found negative by 18F-FDG PET/CT and confirmed by pathology or follow-up. In patient-based analyses, the sensitivity, specificity, and accuracy of 18F-FDG PET/CT for the detection of tumor recurrence were 100% (40/40), 72. 73% (8/11),and 94.12% (48/51) respectively. In 7 patients, the clinical management was changed due to 18F-FDG PET/CT findings. Conclusion 18F-FDG PET/CT is an efficient tool for determining the recurrence of cervical cancer and instructing the clinical management.