1.Neural substrates for regulating self-grooming behavior in rodents
LI GUANQING ; LU CHANYI ; YIN MIAOMIAO ; WANG PENG ; ZHANG PENGBO ; WU JIALIANG ; WANG WENQIANG ; WANG DING ; WANG MENGYUE ; LIU JIAHAN ; LIN XINGHAN ; ZHANG JIAN-XU ; WANG ZHENSHAN ; YU YIQUN ; ZHANG YUN-FENG
Journal of Zhejiang University. Science. B 2024;25(10):841-856
Grooming,as an evolutionarily conserved repetitive behavior,is common in various animals,including humans,and serves essential functions including,but not limited to,hygiene maintenance,thermoregulation,de-arousal,stress reduction,and social behaviors.In rodents,grooming involves a patterned and sequenced structure,known as the syntactic chain with four phases that comprise repeated stereotyped movements happening in a cephalocaudal progression style,beginning from the nose to the face,to the head,and finally ending with body licking.The context-dependent occurrence of grooming behavior indicates its adaptive significance.This review briefly summarizes the neural substrates responsible for rodent grooming behavior and explores its relevance in rodent models of neuropsychiatric disorders and neurodegenerative diseases with aberrant grooming phenotypes.We further emphasize the utility of rodent grooming as a reliable measure of repetitive behavior in neuropsychiatric models,holding promise for translational psychiatry.Herein,we mainly focus on rodent self-grooming.Allogrooming(grooming being applied on one animal by its conspecifics via licking or carefully nibbling)and heterogrooming(a form of grooming behavior directing towards another animal,which occurs in other contexts,such as maternal,sexual,aggressive,or social behaviors)are not covered due to space constraints.
2.Evaluation of tigecycline intraventricular injection regimens in extensively drug resistant Acinetobacter baumannii intracranial infection based on Monte Carlo simulation and pharmacokinetic/pharmacodynamic model
Changxiu LI ; Zhenshan LI ; Han ZHANG ; Fei GAO ; Jin LI ; Jing WANG ; Dapeng HOU ; Yanlin LIU
Chinese Journal of Neuromedicine 2024;23(4):379-386
Objective:To evaluate and screen the regimens of tigecycline intraventricular injection in extensively drug resistant Acinetobacter baumannii (XDRAB) intracranial infection based on Monte Carlo simulation and pharmacokinetic/pharmacodynamic (PK/PD) model.Methods:Nine patients with XDRAB intracranial infection confirmed as having susceptibility to tigecycline or polymyxin antimicrobials from January 1, 2018 to December 31, 2023 were screened from electronic medical record system in Second Affiliated Hospital of Shandong First Medical University. WHONET software was used to extract pathogen susceptibility data isolated from cerebrospinal fluid samples. Minimum inhibitory concentration (MIC) of tigecycline against XDRAB was analyzed by drug susceptibility test; different regimens for intraventricular tigecycline injection were designed based on MIC: 2 mg/12 h, 3 mg/12 h, 4 mg/12 h, 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h, with drug concentration of 0.5 mg/mL or 1.0 mg/mL once a day. Target value of PK/PD index was set as ?C max/MIC≥8; Monte Carlo was used to simulate the compliance of PK/PD index of tigecycline with different MIC against XDRAB for different dosed regimens (probability of target attainment [PTA] and cumulative fraction of response [CFR]); the best regiment was selected (screening basis: PTA≥90% or CFR≥90%). Results:(1) A total of 27 strains of pathogenic bacteria from 9 patients were extracted from drug susceptibility test, in which MIC of tigecycline against XDRAB was 55.56% for 2 mg/L, 25.93% for 4 mg/L, and 18.52% for 8 mg/L. (2) When the drug concentration was 0.5 mg/mL or 1.0 mg/mL, respectively, all 6 regimens had PTA>90% at 2 mg/L MIC; 5 regimens, except for 2 mg/12 h, had PTA>90% at 4 mg/L MIC; regimens of 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h could achieve PTA>90% at 8 mg/L MIC. (3) When the drug concentration was 0.5 mg/mL, regimens of 4 mg/12 h, 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h could achieve CFR>90%; when the drug concentration was 1 mg/mL, regimens of 4 mg/12 h, 5 mg/12 h, 6 mg/12 h, and 10 mg/12 h could achieve CFR>92%.Conclusion:In intraventricular tigecycline injection for XDRAB intracranial infection, 2 mg/12 h regimen is available in 2 mg/L MIC, 3 mg/12 h regimen is available in 4 mg/L MIC, and 5 mg/12 h regimen is available in 8 mg/L MIC, with either 0.5 mg/mL or 1 mg/mL concentration.
3.Comparative Analysis of Serum Pharmacochemistry of Alismatis Rhizoma Before and After Salt Processing Based on UPLC-Q-TOF-MS
Lin YAN ; Zemin OU ; Yanjing WANG ; Yao ZHANG ; Yi CHENG ; Zicheng WANG ; Dewen LIU ; Jinyu WANG ; Zhenshan MA ; Yan TONG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(23):122-130
ObjectiveBased on serum pharmacochemistry and ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) the transitional components in the serum of rats after intragastric administration of water extract of Alismatis Rhizoma(AR)and salt-processed Alismatis Rhizoma(SAR) were compared. MethodSD rats were randomly divided into blank group, AR group(10 g·kg-1) and SAR group(10 g·kg-1), 3 rats in each group, the administration groups were given AR and SAR aqueous extracts by gavage, respectively, and the blank group was given an equal volume of drinking water by gavage once in the morning and once in the evening, for 3 consecutive days. Sixty minutes after the last administration, blood was collected from the eye orbits, and the serum samples were prepared. The serum samples were prepared on an ACQUITY UPLC BEH C18 column(2.1 mm×50 mm, 1.7 μm) with the mobile phase of acetonitrile(A)-0.1% formic acid aqueous solution(B) in a gradient elution(0-10 min, 10%-50% A; 10-27 min, 50%-95%A; 27-27.1 min, 95%-10% A; 27.1-30 min, 10%A), the data were collected at a flow rate of 0.3 mL·min-1 in positive ion mode with a scanning range of m/z 100-1 200. Based on the self-constructed chemical composition library of AR, the total ion flow diagrams and secondary MS fragmentation information of the aqueous extracts of AR and SAR, as well as the administered serum and the blank serum, were compared with each other by UNIFI 1.9.2, so as to deduce the possible blood-migrating constituents and their cleavage patterns in the aqueous extracts, and the response intensity ratios of each chemical component were calculated before and after processing. ResultA total of 20 components, including 5 prototypical components and 15 metabolites, were analyzed and deduced from the serum of rats given aqueous extract of AR. And 14 components, including 5 prototypical components and 9 metabolites, were analyzed and deduced from the serum of rats given aqueous extract of SAR. Of these, 13 components were common to both of them, including 5 prototypical components and 8 metabolites. The 5 prototypical components were 16-oxoalisol A, alisol A 24-acetate, alisol A, alisol B and alisol C. The metabolites were mainly involved in phase Ⅰ metabolism(oxidation) and phase Ⅱ metabolism(glucuronidation). There was a big change in the intensity of response of the common components before and after salt-processing, and the response intensities of the prototypical components, 16-oxoalisol A, alisol B and alisol C, were elevated, while the type and response intensity of metabolites were generally decreased, and it was hypothesized that the metabolic rate of terpenoids might be slowed down after salt-processing of AR, so that the blood-migrating constituents could participate in the metabolism of the body more in the form of prototypes. ConclusionSalt-processing of AR may promote the absorption of prototypical components into the blood by slowing down the metabolic rate of terpenoids, which can provide support for the research on material basis of AR and SAR.
4.Mechanism of Alismatis Rhizoma and Its Processed Product Against Edema of Kidney Yin Deficiency in Rats
Lin YAN ; Zemin OU ; Yanjing WANG ; Yao ZHANG ; Yi CHENG ; Zicheng WANG ; Dewen LIU ; Jinyu WANG ; Zhenshan MA ; Yan TONG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(24):42-49
ObjectiveTo evaluate the pharmacological effect of Alismatis Rhizoma (AR) and its processed product on rats with edema of kidney Yin deficiency and explore the mechanism. MethodA total of 42 male SPF SD rats were randomized into normal group (equivalent volume of distilled water), model group (equivalent volume of distilled water), positive medicine Liuwei Diguangwan group (1.4 g·kg-1), low- and high-dose AR groups (1, 4 g·kg-1, respectively), and low- and high-dose salt-processed AR (SAR) groups (1, 4 g·kg-1, respectively), with six rats in each group. Adriamycin (tail vein injection) and thyroxine (gavage) were used to induce edema of kidney Yin deficiency in rats except the normal group. The administration lasted 4 weeks for all the groups. After the last administration, histopathological changes of rat kidneys were observed based on hematoxylin-eosin (HE) staining. Serum content of triiodothyronine (T3), thyroxine (T4), follicle-stimulating hormone (FSH), and testosterone (T) was determined by radioimmunoassay, and serum content of creatinine (CREA), urea (UREA),cholesterol (CHOL) and triglyceride (TG) by automatic biochemical analyser. The levels of gonadotropin-releasing hormone (GnRH), cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP) in plasma were measured by enzyme-linked immunosorbent assay (ELISA), and the expression of aquaporin(AQP)-1 and AQP-2 and the transcription of mRNA in kidney were measured by immunohistochemistry and real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), respectively. ResultCompared with normal group, the rats in model group showed decrease in body mass and urine volume (P<0.01), increase in water consumption (P<0.05), infiltration of a large number of inflammatory cells and fibrous tissue proliferation in the kidney, rise of the expression and transcript levels of T3, T4, cAMP/cGMP, CREA, FSH, AQP-1, and AQP-2 (P<0.01), the contents of CHOL and TG were significantly increased (P<0.05), and reduction in the levels of GnRH and T (P<0.01). Body mass increased in both the low- and high- dose groups of AR and SAR compared with that in model group, with significant differences between the low-dose AR group and the low-dose SAR group (P<0.01). Moreover, compared with model group, low- and high-dose AR and SAR insignificantly increased the urine volume of rats, reduced the inflammatory cells in kidney tissues, significantly decreased the levels of T4, cAMP/cGMP, UREA, CREA, FSH, CHOL and TG in serum (P<0.05,P<0.01), and elevated the level of GnRH (P<0.01), high-dose AR, low- and high-dose SAR significantly lowered the transcription levels of AQP-1 and AQP-2 mRNA in the kidneys of rats (P<0.01). ConclusionBoth AR and SAR alleviated the edema of kidney Yin deficiency in rats by down-regulating the expression of AQP-1 and AQP-2 and correcting the hypothalamic-pituitary-gonadal (HPG) axis disorder.
5.Clinical observation of the effects of Xihuang pills combined with sodium cantharidinate and vitamin B6 injection in the treatment of tumor-induced fever
Fei LIU ; Yue JIANG ; Zongyu YANG ; Qin MA ; Meng ZHANG ; Zhenshan ZHANG ; Guohua WANG ; Enfeng ZHAO
International Journal of Traditional Chinese Medicine 2018;40(2):116-119
Objective To study the effects of Xihuang pills combined with sodium cantharidinate and vitamin B6 injection in the treatment of tumor-induced fever. Methods A total of 100 patients with tumor-induced fever in our hospital from March 2015 to January 2017 were enrolled in this study. The subjects were divided into the control group (n=50) and the treatment group (n=50) randomly. The control group were treated with aspirin-D L-Lysine injection, and the treatment group were treated with Xihuang pills combined with sodium cantharidinate and vitamin B6 injection. The two groups were treated for 2 periods. The clinical effects of the two groups after treatment were compared. The life quality of the two groups after treatment were compared. The serum TNF-α and IL-1β of the two groups before and after treatment were compared. The adverse reaction rates of the two groups during treatment were compared. Results The total efficacy rate of defervescence of the treatment group was 88.0%(44/50) significantly higher than 56.0%(28/50) of the control group (χ2=12.698, P=0.000). After treatment, the daily life score (1.10 ± 0.18 vs. 2.47 ± 0.21, t=35.025), social communication score (1.21 ± 0.13 vs. 2.53 ± 0.25, t=33.124), mental state score (1.08 ± 0.15 vs. 2.75 ± 0.21,t=45.758), appetite score (1.13 ± 0.16 vs. 2.56 ± 0.19, t=40.708), sleep score (1.22 ± 0.17 vs. 2.71 ± 0.20, t=40.139) of the treatment group were significantly lower than those of the control group (P<0.05). After treatment, the serum TNF-α (1.98 ± 0.07 μg/L vs. 2.86 ± 0.13 μg/L, t=42.144), IL-1β (9.20 ± 1.89 μg/L vs. 13.51 ± 2.36 μg/L, t=10.080) of the treatment group were significantly lower than those of the control group (P<0.05). There was no significantly differences of the adverse reaction rates of the two groups during treatment (χ2=0.211, P=0.646). Conclusions The Xihuang pills combined with sodium cantharidinate and vitamin B6 injection for patients with tumor-induced fever has a good efficacy and low incidence of adverse reactions, can improve the quality of life and reduce the serum levels of TNF-α and IL-1β.
6.Gender differences in femoral component fit and clinical outcomes with unisex total knee prosthesis
Jian WANG ; Aifeng LIU ; Yu ZHANG ; Zhenshan WANG ; Jun LIU ; Lei WANG ; Dongliang ZHANG ; Zhengwei TIAN
Chinese Journal of Orthopaedics 2017;37(23):1474-1482
Objective To determine the effects of gender on distal femoral aspect ratio (DFAR),femoral component fit,and clinical outcomes at 2 years after total knee arthroplasty (TKA).Methods From December 2012 to December 2014,the clinical and radiographic characteristics of 107 consecutive patients (109 knees) were studied prospectively.All patients were divided into two groups according to gender:33 cases (33 knees) were male and 74 cases (76 knees) were female.These subjectives underwent unilateral primary TKAs for end-stage osteoarthritis by using Vanguard high-flex open-box posterior-stabilized fixed-bearing prosthesis.The anterior-posterior size increment of the Vanguard femoral components was 2 mm.The clinical outcomes (Knee Society Score,Western Ontario and McMasters University osteoarthritis index,time-up-to-go test,chair rise test,stair-climbing test,range of flexion,extensor lag,flexion contracture,anterior knee pain score and patient satisfaction) between two groups were compared at 2 years postoperatively.The femoral component fit and two kinds of DFARs were also compared intraoperatively.Results The total overhang value in zone 2 was-5.51±4.46 mm in male and-3.24±3.93 mm in female,respectively.That in zone 3 was-5.99±4.73 mm in male and-3.45±3.98 mm in female.The total underhang value in male was significantly higher than that in female (P<0.05).The rate of significant underhang in zone 3 was significantly higher in male than that in female (60.6%,23.7%,P<O.05).Two kinds of DFARs in male were significantly higher than those in female (1.56±0.12 vs.1.51±0.12,1.28±0.08 vs.1.24±0.11,P<0.05).Compared with intra-operative range of flexion (ROF) in the condition of 90° hip flexion after prosthesis implantation,the loss of ROF against gravity and the loss of passive ROF at 2 years postoperatively were statistically significant higher than those in female (-8.73°±7.71° vs.-4.82°±6.67°,-11.45°±8.78° vs.-7.34°±8.71°,P<0.05).In the male group,the natural ROF after capsule closed (132.85°±6.01°) was significantly larger than that of the female group (128.78°±6.34°),but there was no significant difference in passive flexion.The change of non-weight-bearing passive ROF (1.67°± 14.76°),the Knee Society stairclimbing score (45.15±7.12) and the proportion of being able to squat and rise (97.0%) in male group were greater than those in female group,postoperatively.Conclusion Although DFAR is different within gender;it has little effects on early outcomes after unisex posterior-stabilized TKA.The loss of ROF in male is more prominent than that in female.Increased size offerings of femoral components improve fit in female distal femur.However,distal femur of male still exist obvious underhang.
7.Effect of hypoxic preconditioning on sphingosine kinase-1 expression and blood-brain barrier permeability in rats after traumatic brain injury
Yinsheng YAO ; Jiachuan LIU ; Yanyan YANG ; Xing ZHANG ; Zhenshan HUANG ; Yudong WEN
Chinese Journal of Neuromedicine 2014;13(7):672-676
Objective To explore the effect ofhypoxic preconditioning (HPC) on the expression of sphingosine kinase-1 (SphK-1) and blood-brain barrier (BBB) permeability in rats after traumatic brain injury (TBI).Methods Two hundred and four SD rats were randomly assigned into TBI group (n=96),HPC group (giving HPC and TBI,n=96) and blank control group (n=12).The rats in the TBI group were subjected to TBI with freefall impact method,while the rats of HPC group were treated with the same methods after HPC (50.47 kpa,3 d,3 h/d).And then,they were sacrificed at each time point (1,4,8 and 12 h,and 1,3,7 and 14 d after injury).RT-PCR and Western blotting were employed to detect the mRNA and protein expression changes of SphK-1 in brain contusion area at each time points after injury.Immumohistochemical staining (IgG method) was used to detect the BBB permeability changes of the rats.Results IgG scores and Sphk-1 mRNA and protein expressions in rats of TBI group and HPC group began to increase at 1 h after injury and reached the highest level 1 d after injury; they were still higher than the normal levels,with significant differences (P<0.05); SphK-1 mRNA and protein expressions in all the three groups had the same increased trend at all the time points excepted on the 14th d of injury,with significant differences (P<0.05).IgG scores showed that the BBB permeability in the TBI group at each time point was significantly higher than that in the HPC group (P<0.05).Conclusion Hypoxic preconditioning can increase SphK-1 expressions after TBI to promote sphingosine 1-phosphate sphingosine transformation so as to protect of the integrity of BBB.
8.Magnetic resonance spectroscopic study on regional cerebral metabolic changes of rabbits with explosive brain injury
Yanyan YANG ; Jiachuan LIU ; Yongming ZHANG ; Wenjiang SUN ; Hong TANG ; Zhenshan HUANG ; Bingcang LI ; Liangchao ZHANG
Chinese Journal of Trauma 2011;27(4):375-378
Objective To evaluate the regional cerebral metabolic changes in different episodes by magnetic resonance spectroscopy (MRS) after explosive brain injury in rabbits. Methods Fortyfive New Zealand white rabbits were randomly divided into eight groups, ie, normal control group( 10 rabbits) and trauma group (35 rabbits). The explosive injury in trauma group was induced by explosion of 600 mg TNT equivalent of paper detonators at 6.5 cm above the rabbit brain. The rabbits in trauma group was divided into 1,6, 12, 24 hours, 3, 7, 14 days subgroups (6 rabbits per group). The survival rate was observed at different time points after explosive injury. The MRS was used to detect the regional cerebral metabolic changes including N-acetylaspartate (NAA)/creatine (Cr) ratio and choline(Cho)/Cr ratio as well as evolution of blast injuries over time. Results The rabbits survived for overseven days in the trauma groups, with typical brain contusion manifested by pathological and conventional MRI. Compared with the normal control group, the NAA/Cr ratio was markedly decreased at one hour after injury, slightly rose again at 24 hours and fell again after seven days. The Cho/Cr ratio was markedly increased at one hour after injury, slightly fell again at 12 hours and rose again at three days after injury.Conclusions MRS can manifest the regional cerebral metabolic changes of rabbits with explosive injury at different time points and hence provide a theoretical basis for understanding the local tissue changes and determining the type of tissue damage after blast injury.
9.Distribution of uranium in rata inhaled with depleted uranium aerosols
Xiujie PAN ; Zhihua YANG ; Zhenshan CAO ; Ping LI ; Gang LIU ; Zhongmin CHEN ; Han WEI ; Maoxiang ZHU
Chinese Journal of Radiological Medicine and Protection 2009;29(1):23-26
Objective To investigate the distribution of uranium in rats after inhalation with depleted uranium aerosols. Methods The depleted uranium aerosols were inhaled by Wistar rats. At 30, 90, 180, 270, 360, and 540 d after inhalation, the rata were sacrificed and tissue samples were collected. The contents of uranium in lung, kidney, liver, heart, brain, thighbone, spleen and thymus were measured by laser time-dependent spectroscopy analysis. Resulits The uranium contents of lung increased in the high-dosc and low-dose groups [(499833.3 ± 14214.8) ng/g and (25 424.0 ± 6193.4)ng/g, respectively] after inhalation, and significantly differed from the control (28.8 ± 13.9)ng/g, (P < 0.05).At 30 d after inhalation, the contents of uranium in lung, kidney and thighbone were higher than those of control, and then decreased time-dependently. At 60 d, the contents of uranium in liver, heart, brain, spleen and thymus were higher than those of control. Curve of the eontenta were biphasie, whieh went up first, reached at peak value and then went down. The contents of uranium were high in lung, thighbone, brain and thymus. Conclusions After inhalation of depleted uranium aerosols, lung and thighbone are the primary reservoirs for uranium redistributed, and accumulations in brain and thymus suggest other two organs for unanticipated injury by depleted uranium.
10.Clinical observation of lumbar muscle strain treated by Biqi Capsule
Songjie XU ; Xueming CHEN ; Libin CUI ; Yadong LIU ; Xin YUAN ; Zhenshan YU
China Journal of Traditional Chinese Medicine and Pharmacy 2005;0(06):-
Objective:To study curative effect of Biqi Capsule on lumbar muscle strain. Methods:120 patients who meet the full diagnostic criteria were grouped into the treatment group (66 patients) and the control group (54 patients) at random. The treatment group was treated with Biqi Capsule per os,while the control group was treated with western medicine Composite Chlorzozazone tablets per os.The comprehensive curative effects on the two groups were summarized.Results:The total effective rate of the treatment group and the control group were 92.4% and 79.6% respectively;No significant differences in two groups in statistics (P=0.06).The VAS score of the treatment group and the control group were (0.95?1.63) and (1.83?2.39) respectively.The curative effect was found to be better in the treatment group than that in the control group (P

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