1.Effects of borneol on pharmacodynamics and pharmacokinetics of Corydalis saxicola total alkaloids in depression model rats
Yu YE ; Guoliang DAI ; Huaxi HANG ; Meishuang YU ; Yiran WANG ; Xuewen SHAO ; Wenzheng JU
China Pharmacy 2025;36(1):30-36
OBJECTIVE To investigate the effects of borneol on pharmacodynamic and pharmacokinetic effects of Corydalis saxicola total alkaloids in depression model rats. METHODS Thirty male SD rats were divided into blank control group, negative control group, positive control group (fluoxetine 10 mg/kg, i.g.), single drug group (C. saxicola total alkaloids 210 mg/kg, i.g.) and combined drug group (C. saxicola total alkaloids 210 mg/kg+borneol 50 mg/kg, i.g.) according to the random number table method, with 6 rats in each group. By lipopolysaccharide (LPS) induction modeling, except blank control group (no model and no administration) received intraperitoneal injection of the same amount of normal saline, the rats in the other groups were intraperitoneally injected with LPS once a day to establish a rat model of depression. After 1 week of modeling, each administration group was given relevant drug intragastrically according to the corresponding dose, and blank control group and negative control group (without drug treatment) were administered intragastrically with an equal volume of solvent to dissolve the drug; continued modeling while administering the drug. After two weeks of continuous administration, the effects of C. saxicola total alkaloids versus the combination of C. saxicola total alkaloids and borneol on the behavior of depressed rats were tested by behavioral experiments; the levels of tumor necrosis factor-α, interleukin-1β and interleukin-6 in rats were determined; the histopathological changes of the hippocampus of rats were observed. Blood sample was collected from the orbit at different time points after administration on the 15th day, and the upper plasma was obtained. Ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry was established for the simultaneous determination of dehydrocarvedine, tetrahydropalmatine, coptisine, palmatine, jatrorrhizine, berberine, berberrubine and epiberberine in rat plasma. The average plasma concentration-time curve was depicted, the area under the curve (AUC) was calculated, and the pharmacokinetic parameters were analyzed by DAS 3.2.2 software. RESULTS Compared with blank control group, the negative control group had a decrease in body mass and sugar water preference rate, a decrease in the total distance of open field, a prolonged swimming immobility time, and a increased in the expression of inflammatory factors in serum (P<0.05); compared with negative control group, the single drug group and the combined drug group increased the preference rate of sugar water, increased the total distance of open field, shortened the time of swimming immobility, and decreased the expression of inflammatory factors in serum (P<0.05). There was no significant difference in the above indicators between the single drug group and the combined drug group in rats (P>0.05). Pharmacokinetic results showed that compared with single drug group, AUC0-t of coptisine, AUC0-t, AUC0-∞, tmax and cmax of jatrorrhizine, AUC0-t, AUC0-∞, t1/2 and cmax of berberrubine, and AUC0-t of epiberberine, cmax of dehydrocarvedine, cmax of palmatine were significantly increased in combined drug group, but there was no significant difference, indicating that borneol didn’t have a significant effect on the efficacy of Corydalis saxicola nigra at this dose. CONCLUSIONS Both C. saxicola total alkaloids alone and in combination with borneol can improve depression-like behavior in depression model rats, reduce serum inflammatory cytokine levels, and protect hippocampal neurons. Compared with the use of Corydalis saxicola base alone, the combination with borneol do not show significant pharmacodynamic differences, bu can improve the absorption of coptisine, jatrorrhizine in model rats.
2.Exploration of the Intervention Mechanism of Qingshi Anti-itch Ointment (青石止痒软膏) on Psoriasis Model Mice Based on Caspase-1/GSDMD Protein Pathway
Yatong LI ; Yuanwen LI ; Yutong DENG ; Xuewen REN ; Xuewan WANG ; Xinhui YU ; Tangyunni LIU
Journal of Traditional Chinese Medicine 2025;66(2):170-177
ObjectiveTo explore the possible action mechanism of Qingshi Anti-itch Ointment (青石止痒软膏, QAO) in the treatment of psoriasis. MethodsForty mice were randomly divided into four groups, blank group, model group, calcipotriol group and QAO group, with 10 mice in each group. Except for the blank group, psoriasis was induced by applying imiquimod cream to the dorsal skin. After modeling for 6 hours daily, the calcipotriol group and QAO group were treated with 0.5 g of calcipotriol ointment or 0.5 g of QAO, respectively, applied to the treated dorsal skin. The blank group and the model group received no treatment. The skin lesions were observed, and the psoriasis area and severity index (PASI) score was assessed every other day. After 7 days, Hematoxylin and Eosin (HE) staining was performed on dorsal skin tissue to observe pathological changes. The levels of interleukin 1β (IL-1β) and interleukin 18 (IL-18) were determined by enzym-linked immunosorbent assay (ELISA). The protein levels of Caspase-1,Pro-Caspase-1, gasdermin D (GSDMD) and gasdermin-D-N (GSDMD-N) were detected by Western Blot (WB). The protein levels of GSDMD were observed by immunohistochemistry. ResultsCompared with the blank group, the model group mice showed redness, erythema, and white scales on their skin, with histological observations indicating epidermal thickening, elongated spines, and infiltration of inflammatory cells. The PASI scores of the skin tissue on days 1, 3, 5, and 7 were elevated; the IOD and AOD values of GSDMD protein increased; the protein levels of Caspase-1, Pro-Caspase-1,GSDMD, GSDMD-N, and IL-1β and IL-18 were significantly elevated (P<0.05 or P<0.01). Compared with the model group, the QAO group and calcipotriol group showed lighter skin lesions; the PASI scores on day 5 and day 7 in the QAO group, and on day 3, 5, and 7 in the calcipotriol group, were reduced; the IOD and AOD values of GSDMD protein, and the protein level of Caspase-1, GSDMD, and GSDMD-N, as well as level of IL-18 and IL-1β decreased in both groups; in the calcipotriol group, Pro-Caspase-1 protein level also decreased (P<0.05 or P<0.01). Compared with the calcipotriol group, the QAO group showed slightly redder skin, more obvious thickening of the stratum corneum, and less capillary dilation; the PASI scores on day 3 and day 7 increased, while the score on day 5 was reduced; the protein level of Pro-Caspase-1, GSDMD, GSDMD-N, and the level of IL-18 and IL-1β were increased in the QAO group (P<0.05). ConclusionQAO can effectively relieve psoriasis dermatitis in mice. Its potential mechanism may be related to the regulation of the Caspase-1/GSDMD protein pathway, down-regulation of IL-18 and IL-1β levels, and alleviation of pyroptosis.
3.Effect of finite element method in treatment of developmental dysplasia of the hip in children
Xiaojun SUN ; Huaming WANG ; Dehong ZHANG ; Xuewen SONG ; Jin HUANG ; Chen ZHANG ; Shengtai PEI
Chinese Journal of Tissue Engineering Research 2025;29(9):1897-1904
BACKGROUND:Developmental dysplasia of the hip often leads to limb deformities in children,and the research related to its diagnosis and treatment has been gradually clarified.Recently,the finite element method has been paid attention to by scholars in the research related to developmental dysplasia of the hip because of its advantages. OBJECTIVE:Through literature search and review of the relevant research progress of finite element method in children's developmental dysplasia of the hip and treatment,analyze and summarize its advantages and disadvantages,and explore the direction of further research in the future. METHODS:PubMed,SCI,CBM,and CNKI were searched for relevant articles published from January 2014 to November 2023 with the key words of"developmental dysplasia(dislocation)of the hip,dysplasia of the hip,finite element analysis(method),pavlik harness,fixation in herringbone position,biomechanics,pelvic osteotomies,pemberton,salter,dega,periacetabular osteotomy,children"in Chinese and English.A small number of long-term articles were included,and 62 articles were finally included for analysis through screening. RESULTS AND CONCLUSION:(1)The mechanical environment of hip joint in children with developmental dysplasia of the hip was abnormal.The pressure in acetabulum was uneven.The stress increased and concentrated;the joint contact area decreased,and the local stress concentrated in femoral neck.(2)In the Pavlik sling and herringbone fixation,the mechanical environment of the hip was improved;the concentrated high stress area disappeared and the joint contact area increased,but the excessive abduction angle led to the increase of stress in the acetabulum and the lateral femoral head.(3)After pelvic osteotomy,the stress environment of hip joint and sacroiliac joint was improved.There was no single hinge in the three kinds of osteotomy,and the stress load position was different according to the age of the children.(4)After peri-acetabular osteotomy,the joint contact pressure was close to normal,but it was difficult to recover in patients with non-spherical femoral head.(5)The postoperative X-ray film findings could not show that the joint contact mechanics was the best.(6)It is indicated that the information that cannot be measured in the body can be obtained by using the finite element method,which can be operated in a virtual environment without the limitation of time and ethics.It can directly see the stress change area of normal and developmental dysplasia of the hip,explain the effectiveness of treatment from the point of view of mechanics,establish a specific finite element model and tailor-made operation plan for patients who need osteotomy.There is no standard or unified standard for the finite element modeling of developmental dysplasia of the hip and the material characteristic parameters of children's hip joint.Due to the inherent limitations of finite element method,it is impossible to analyze the model that contains bone,cartilage,ligament,muscle and other elements at the same time.The operation of finite element analysis is difficult,although it has advantages,it is not universal,and the current research sample size is small,which needs to be further expanded and verified.
4.A Randomized Controlled,Double-Blind Study on Huaban Jiedu Formulation (化斑解毒方) in the Treatment of Psoriasis Vulgaris with Blood-Heat Syndrome
Xuewen REN ; Yutong DENG ; Huishang FENG ; Bo HU ; Jianqing WANG ; Zhan CHEN ; Xiaodong LIU ; Xinhui YU ; Yuanwen LI
Journal of Traditional Chinese Medicine 2025;66(16):1679-1686
ObjectiveTo evaluate the clinical efficacy and safety of Huaban Jiedu Formulation (化斑解毒方, HJF) in treating psoriasis vulgaris with blood-heat syndrome. MethodsA randomized, double-blind, placebo-controlled study was conducted with 60 patients diagnosed with psoriasis vulgaris of blood-heat syndrome. Patients were randomly assigned to either a treatment group or a control group, with 30 cases in each. The treatment group received HJF granules orally, one dose a day, combined with topical Qingshi Zhiyang Ointment (青石止痒软膏), while the control group received placebo granules, one dose a day, combined with the same topical ointment. Both groups were topically treated twice daily of 28 days treatment cours. Psoriasis area and severity index (PASI), visual analogue scale for pruritus (VAS), traditional Chinese medicine (TCM) syndrome scores, dermatology life quality index (DLQI), and psoriasis life stress inventory (PLSI) were assessed before treatment and on day 14 and day 28. Response rates for PASI 50 (≥50% reduction) and PASI 75 (≥75% reduction), as well as overall clinical efficacy, were compared between groups. Serum levels of interleukin-6 (IL-6) and interleukin-17 (IL-17) were measured before and after 28 days of treatment. Adverse reactions during treatment were recorded. ResultsAfter 28 days of treatment, both groups showed significant reductions in PASI total score, lesion area score, erythema, scaling, and infiltration scores, pruritus VAS score, TCM syndrome score, DLQI, PLSI, and serum IL-6 and IL-17 levels (P<0.05). Compared to the control group, the treatment group had significantly greater improvements in PASI total score and erythema score, TCM syndrome score, serum IL-6 and IL-17 levels, and PASI 50 response rate after 28 days (P<0.05). Between-group comparisons of score differences before and after 28-day treatment revealed that the treatment group showed significantly better improvements in PASI total, lesion area score, erythema score, TCM syndrome score, DLQI, PLSI, and inflammatory markers (P<0.05 or P<0.01). The total effective rate on day 14 and day 28 was 40.00% (12/30) and 83.33% (25/30) in the treatment group, versus 6.90% (2/29) and 41.38% (12/29) in the control group, respectively. The clinical efficacy in the treatment group was significantly superior to that in the control group (P<0.05). Mild gastric discomfort occurred in 3 patients in the treatment group and 1 in the control group. ConclusionHJF can effectively improve skin lesions and TCM symptoms relieve pruritus, enhance quality of life, and reduce inflammatory markers IL-6 and IL-17, in patients with blood-heat syndrome of psoriasis vulgaris, with a good safety profile.
5.Effect of Borneol on Pharmacodynamics,Pharmacokinetics and Brain Tissue Distribution of Main Active Ingredients of Jiaotaiwan in Depression Model Rats
Meishuang YU ; Guoliang DAI ; Huaxi HANG ; Yu YE ; Yiran WANG ; Xuewen SHAO ; Wenzheng JU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):18-27
ObjectiveTo investigate the pharmacodynamics, pharmacokinetics and brain distribution of seven main components of Jiaotaiwan alone and Jiaotaiwan combined with borneol in lipopolysaccharide(LPS)-induced depression rats. MethodRats were randomly divided into the control group, model group, fluoxetine group(10 mg·kg-1), Jiaotaiwan group(1.5 g·kg-1) and combination group(1.5 g·kg-1 of Jiaotaiwan+0.05 g·kg-1 of borneol), with 8 rats in each group. Except for the control group, the depression model was established by intraperitoneal injection of LPS for 7 consecutive days, and each group was given the corresponding drugs or the same volume of pure water by gavage for 14 consecutive days. The behavioral indicators and levels of serum inflammatory factors[interleukin-1β(IL-1β), IL-6 and tumor necrosis factor-α(TNF-α)] of rats in each group were compared. The morphological changes of hippocampal neurons were observed by hematoxylin-eosin(HE) and Nissl staining. After the behavioral tests of sucrose preference, open field and forced swimming were completed, blood samples were collected from Jiaotaiwan group and combination group at the set time points after gavage, the contents of seven components in plasma were determined by ultra performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS/MS), and the pharmacokinetic parameters of each component were analyzed by DAS 3.2.2. Brains were rapidly removed on ice after blood collection was completed, and UPLC-QqQ-MS/MS was used to compare the content changes of the 7 components in brain tissue. ResultCompared with the control group, rats in the model group showed decreased sucrose preference rate and total distance of open field, prolonged swimming immobility time, and increased expression of inflammatory factors in serum(P<0.01). Compared with the model group, the sucrose preference rate and total distance of open field were increased, and the swimming immobility time was shortened in the rats of each administration group, and the expression of inflammatory factors in serum was decreased in rats from Jiaotaiwan group and combination group(P<0.05, P<0.01). The results of HE and Nissl staining showed that Jiaotaiwan group and combination group had a certain protective effect on hippocampal neurons. The pharmacokinetic results showed that compared with Jiaotaiwan group, the area under the curve(AUC0-t, AUC0-∞), peak concentration(Cmax) and the average steady-state plasma concentration(Cav) of berberine and epiberberine in the combination group were increased(P<0.05, P<0.01), AUC0-t, AUC0-∞, mean residence time(MRT0-∞) and Cav of coptisine were significantly increased(P<0.05, P<0.01), Cmax of jatrorrhizine increased significantly(P<0.05), but the pharmacokinetic changes of the seven alkaloids were consistent. The results of brain tissue distribution showed that compared with Jiaotaiwan group, the contents of jatrorrhizine, epiberberine, coptisine, palmatine and berberine in the brain tissue of combination group were increased(P<0.05, P<0.01), the content of magnoflorine increased and that of berberrubine decreased, but the difference was not statistically significant. ConclusionJiaotaiwan alone or combined with borneol can improve the depression-like behavior of rats, reduce the levels of serum inflammatory factors, improve the pathological damage of hippocampus, and have antidepressant effect. Compared with Jiaotaiwan alone, the combination of Jiaotaiwan and borneol can increase the exposure of multiple active components of Jiaotaiwan in the plasma and brain tissue of rats, improve its bioavailability, promote its absorption, and improve the brain targeting of the drug, which is more conducive to the antidepressant effect of Jiaotaiwan.
6.The early prediction of umbilical cord blood S100β protein and lactate combined with amplitude integrated electroencephalogram in small for gestational age preterm infants with brain injury
Junlong CHEN ; Xiaoli WANG ; Xiaoling YANG ; Xuewen SU ; Fuhua JIA ; Shuli WU
International Journal of Pediatrics 2024;51(1):64-68
Objective:To explore the early predictive value of umbilical cord blood S100β protein and lactate combined with amplitude integrated electroencephalogram(aEEG)in small for gestational age(SGA)preterm infants with brain injury.Methods:One hundred and six cases of SGA preterm infants were enrolled in this study in Neonatology Department of Inner Mongolia People's Hospital from January 2019 to December 2021. Umbilical cord blood serum S100β protein and lactate at birth of All SGA preterm infants were tested,and aEEG was monitored at 6h and 72 h after birth,corrected gestational age of 32 weeks and 37 weeks. According to the diagnostic criteria of brain injury in preterm infants,SGA preterm infants were divided into brain injury group(45 cases)and non-brain injury group(61 cases),and compared the differences of S100β protein,lactate and the designated time aEEG between the two groups.SGA preterm infants with brain injury were further divided into symmetrical group(28 cases)and non-symmetrical group(15 cases). The differences of umbilical cord blood S100β protein and lactate level between the two groups were compared,and the diagnostic value in different types of SGA preterm infants with brain injury was also compared.Results:SGA preterm infants in the brain injury group had significantly higher levels of umbilical cord blood S100β protein[(0.826±0.218)μg/L vs(0.397±0.196)μg/L, t=8.316, P<0.05]and lactate[(8.5±1.3)mmol/L vs(3.8±0.9)mmol/L, t=3.281, P<0.05]than those in non-brain injury group.Symmetric SGA group had higher level of S100β protein than the asymmetric SGA group[(0.924±0.205)μg/L vs(0.438±0.196)μg/L, t=5.734, P<0.05].But there was no statistically significant difference in lactate levels[(5.6±1.4)mmol/L vs(3.9±1.2)mmol/L, t=0.932, P>0.05]between symmetric SGA group and asymmetric SGA group. The abnormal rates of aEEG in brain injury group and non-brain injury group were respectively 100%(45/45)vs 22.95%(14/61)at 6 h after birth,95.56%(43/45)vs 16.39%(10/61)at 72 h after birth,62.22%(28/45)vs 6.56%(4/61)at 32 weeks of corrected gestational age,22.22%(10/45)vs 3.28%(2/61)at 37 weeks of corrected gestational age. The abnormal rate of brain injury group was higher than the non-brain injury group in the same nodal time,and the differences were statistically significant( χ 2 value respectively 62.292,64.913,38.074,9.257,all P<0.05). Conclusion:There were significant value in umbilical cord blood S100β protein,lactate level and aEEG monitoring in the early diagnosis in preterm infants SGA with brain injury. The combination of the three might be more helpful for the early diagnosis and timely treatment of brain injury in SGA preterm infants.
7.Pharmacokinetics of Total Alkaloids of Corydalis saxicola in Depression Model Rats
Huaxi HANG ; Meishuang YU ; Yu YE ; Qian HUANG ; Yiran WANG ; Xuewen SHAO ; Peiyao CHEN ; Yang CAO ; Guoliang DAI ; Wenzheng JU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):175-183
ObjectiveTo investigate the effect of total alkaloids of Corydalis saxicola on a rat model of lipopolysaccharide(LPS)-induced depression, as well as the pharmacokinetic characteristics of 8 of its major components. MethodTwenty-four male SD rats were randomly divided into normal group, model group, fluoxetine group(10 mg·kg-1) and total alkaloids of C. saxicola group(210 mg·kg-1), with 6 rats in each group. In addition to the normal group, the rats were injected intraperitoneally with LPS to establish the inflammation model of depression, and the drug administration was started 1 week after modeling, and the administration groups were gavaged according to the corresponding dose, and the normal and model groups were intragastric administration with equal volume of distilled water, and the administration was performed along with the modeling. After two weeks of continuous administration, the effect of total alkaloids of C. saxicola on the behavior of depressed rats were tested by sucrose preference, forced swimming and open field experiments, the levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-6 in serum of rats were determined by enzyme-linked immunosorbent assay(ELISA), the histopathological changes of rat hippocampus were observed by hematoxylin-eosin(HE) staining. After the last administration, blood was collected from orbit according to the set time, and ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS) was established to simultaneously detect the concentrations of dehydrocavidine, tetrahydropalmatine, coptisine, palmatine, jatrorrhizine, berberine, berberrubine and epiberberine in plasma, and drug-time curves were drawn. The pharmacokinetic parameters were analyzed by DAS 2.0 software. ResultCompared with the normal group, the model group exhibited a decrease in sucrose preference rate, total distance traveled in the open field, as well as an increase in swimming immobility time and serum inflammatory factor expression(P<0.01). In contrast, compared with the model group, rats in each administration group showed an increase in sucrose preference rate and total distance traveled in the open field, a decrease in swimming immobility time, and a reduction in serum inflammatory factor expression(P<0.05, P<0.01). Additionally, HE staining results revealed that neurons in the hippocampus of rats from the model group were characterized by loss, disorganization and residual vacuoles, whereas those from the total alkaloids of C.saxicola group displayed an increase in number with orderly arrangement and clear cytoplasm. Pharmacokinetic results showed that the time to peak(tmax) and half-life(t1/2) of the 8 active ingredients were 0.19-2.06 h and 3.71-8.70 h after continuous administration of total alkaloids of C. saxicola. Among them, the area under the curve(AUC0-∞) of tetrahydropalmatine was the highest and the t1/2 was the shortest, and the AUC0-∞ of coptisine, palmatine, jatrorrhizine, berberine, berberrubine and epiberberine were low. The curves of dehydrocavidine, coptisine, palmatine, berberine and epiberberine showed obvious double peak phenomenon. ConclusionTotal alkaloids of C. saxicola can improve the depression-like behavior of rats, inhibit the expression of inflammatory factors in serum, improve the pathological injury of hippocampus, and has the antidepressant effect. Meanwhile, the effective site is absorbed quickly and eliminated slowly in the depressed model rats, and the efficacy is maintained for a long time.
8.Clock genes regulate the browning of white fat in obese rats undergoing hypoxia exercise
Dongzi SHI ; Hua ZHANG ; Chang MENG ; Xinrui LI ; Panpan DONG ; Xuewen TIAN ; Qinglu WANG
Chinese Journal of Tissue Engineering Research 2024;28(16):2473-2480
BACKGROUND:Hypoxic exercise can promote the degradation of body fat,and changes in the external environment can affect the circadian rhythm of animals,but the mechanisms by which changes in circadian rhythm regulate adipose tissue browning and fat degradation are unclear. OBJECTIVE:To elucidate the mechanism of clock gene regulation on epididymal adipose tissue Browning in obese rats undergoing hypoxia exercise. METHODS:Forty obese rats were randomly selected and divided into four groups(n=10 per group):normoxic sedentary group,hypoxic sedentary group,normoxic exercise group,and hypoxic exercise group for 4 weeks of intervention.The rats in the sedentary groups were not intervened,while those in the hypoxic groups lived in a hypoxic chamber with an oxygen concentration of 13.6%for the whole day.In the exercise groups,adaptive training was performed in the 1st week,and the speed and length of training remained unchanged for the last 3 weeks.The body mass,body length and perirenal fat mass of obese rats were measured.Serum levels of triacylglycerol,total cholesterol,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol in obese rats were detected by a biochemical assay kit.Liver fat content was observed by oil red O staining.Hematoxylin-eosin staining was used to evaluate the browning of epididymal adipose tissue of rats in different groups.RNA sequencing combined with bioinformatics analysis was used to analyze transcriptome changes in adipose tissue.The mRNA expressions of PGC-1α,Beclin 1,KLF 2 and Perilipin 1 in epididymal adipose tissue were detected by RT-PCR. RESULTS AND CONCLUSION:Hypoxic exercise intervention significantly decreased body mass,body fat percentage,Lee's index,serum triacylglycerol,total cholesterol,and low-density lipoprotein cholesterol levels(P<0.01),and significantly increased high-density lipoprotein cholesterol level(P<0.01).Oil red O staining and hematoxylin-eosin staining results showed that hypoxic exercise was more effective in promoting fat mobilization in liver tissue and promoting the browning of parepididymal adipose tissue compared with normoxic sedentary group,hypoxic sedentary group,and normoxic exercise group.RNA-seq results showed that hypoxic exercise significantly upregulated the expression of clock genes Dbp,Nr1d1,Sik1 and adipose tissue browning gene Ppargc1a(PGC-1α)and downregulated the expression of Arntl(Bmal1),accompanied by the enhanced expression of genes related to substance metabolism.qRT-PCR indicated that hypoxic exercise significantly increased the mRNA expression levels of PGC-1α and Perilipin1(P<0.01).Therefore,these findings indicate that clock genes play an important role in promoting adipose tissue browning during hypoxic exercise.
9.Effect of moderate-intensity exercise on the level of autophagy in bone tissue of ovariectomized rats
Xun LI ; Weichao ZHANG ; Yingjie LI ; Rong LIU ; Xuewen TIAN ; Pengyi ZHANG ; Xiaoqiang WANG
Chinese Journal of Tissue Engineering Research 2024;28(20):3130-3136
BACKGROUND:Exercise is an effective method for preventing and treating osteoporosis,but it is unclear whether its effect on postmenopausal osteoporosis is related to changes in bone autophagy levels. OBJECTIVE:To observe the effects of exercise via cellular autophagy on the morphology and mechanical properties of bone tissue in ovariectomized rats,and to explore the mechanism of exercise on bone mass in ovariectomized rats from the perspective of autophagy. METHODS:A rat model of postmenopausal osteoporosis was established,and a 24-week moderate-intensity exercise was used for intervention.After the experiment,serum estradiol levels were measured by ELISA,and bone mineral density and bone microstructure of the cortical and trabecular bone were detected by micro-CT.The biomechanical indicators of the tibia were tested by a three-point bending test.Autophagosomes were observed by transmission electron microscopy.The expression of LC3 and ATG7 proteins was analyzed by western blot. RESULTS AND CONCLUSION:The serum estradiol level in the ovariectomized group was significantly lower than that of the sham-operation group and ovariectomized+exercise group(P<0.01).The body mass of rats in each group increased,and the order was the ovariectomized group>the ovariectomized+exercise group>the sham-operation group>the sham-operation+exercise group.The bone mineral density and bone mass of rats in all groups significantly increased(P<0.01),but the increase in the ovariectomized group was significantly lower than that of the other groups,and the increase in the ovariectomized+exercise group was significantly higher than that of the ovariectomized group.Compared with the sham-operation group,the bone mineral density of the tibial cancellous bone in the sham-operation+exercise group was significantly increased(P<0.01),while the bone mineral density in the ovariectomized and ovariectomized+exercise groups was significantly decreased(P<0.01).Compared with the ovariectomized+exercise group,the ovariectomized group showed significantly lower bone volume fraction,number of trabeculae,and bone mineral density of cancellous bone(P<0.05),extremely significantly lower trabecular thickness(P<0.01),and significantly higher mean trabecular pattern factor,trabecular separation,and structural model index(P<0.01).Compared with the ovariectomized group,the LC3-Ⅱ/LC3-I ratio and the relative expression of ATG7 protein significantly increased in the ovariectomized+exercise group(P<0.05).Compared with the sham-operation and ovariectomized groups,the number of autophagosomes increased in the sham-operation+exercise and ovariectomized+exercise groups,respectively.To conclude,moderate-intensity treadmill exercise can improve the bone microstructure and biomechanical properties of the tibial cancellous bone and increase bone mass in ovariectomized rats by increasing serum estradiol levels and bone autophagy levels.
10.Special application of stone extractor balloon catheter in ERCP for anastomotic biliary stenosis after liver transplantation
Xuan WANG ; Xuewen CHEN ; Jinxin HUANG ; Jiajun CHEN ; Yan QU ; Hao GAO ; Biao GONG ; Xiwen ZHANG ; Fu LI
China Journal of Endoscopy 2024;30(3):7-13
Objective To discuss the application effect of using a stone extractor balloon catheter to assist in crossing the anastomotic stenosis in treatment of anastomotic biliary stenosis after liver transplantation using endoscopic retrograde cholangiopancreatography(ERCP).Methods Clinical data of 48 patients who developed anastomotic biliary stenosis after liver transplantation and underwent ERCP treatment were collected.Upon unsuccessful use of a dilation catheter to cross the stricture,attempts were made to cross the anastomotic biliary stenosis by using a stone extractor balloon catheter.The success rate of the procedure was recorded,intraoperative conditions were observed,treatment outcomes and complications were analyzed.Results The main presenting symptoms in the 48 patients on admission were abdominal discomfort(32 patients),fever(7 patients),pruritus(4 patients),jaundice(3 patients),and no obvious symptoms(2 patients).Preoperative magnetic resonance cholangiopancreatography(MRCP)examination revealed isolated stricture of the anastomotic site in 35 cases,and stricture associated with stones in 13 cases.Using the stone extractor balloon catheter as a guide,guidewire crossing of the anastomotic stenosis was successful in 26 cases,resulting in a success rate of 54.17%(26/48).Through statistical analysis of the successful group and the failed group,there was a significant difference in whether the distal biliary dilatation between the two groups,and the difference was statistically significant(χ2 = 8.39,P = 0.004).In the 26 successfully treated cases,alanine transaminase(ALT),aspartate transaminase(AST),γ-glutamyl transpeptidase(γ-GT),alkaline phosphatase(ALP),and total bilirubin(TBiL)levels decreased significantly 48 hours after the procedure(P<0.05),and no serious complications occurred.Conclusion The use of a stone extractor balloon catheter significantly increases the success rate of crossing anastomotic stenosis in the treatment of anastomotic biliary stenosis after liver transplantation,especially in cases with distal dilatation of the common bile duct.This approach is safe and worth promoting.

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