[Electroacupuncture intervention improves lipid metabolism and promotes browning of white adipose tissue by activating AMPK/Sirt1 pathway and up-regulating Nrg4 content in middle-aged and aged obese rats].

OBJECTIVE: To investigate the mechanism of electroacupuncture （EA） in promoting the browning of white adipose tissue in middle-aged and aged obese rats induced by high fat by regulating AMP-activated protein kinase （AMPK） /silence-information regulatory factor 1 （Sirt1） pathway and neuregulin 4 （Nrg4）. METHODS: Twenty-four male SD rats were randomized into blank control, model and EA groups （n=8 per group）. The obesity model was established by feeding the rats with high-fat diet for 6 weeks. For the EA group, EA （2 Hz/15 Hz, 1.5 mA） was applied to "Guanyuan" （CV4） and bilateral "Shenshu" （BL23）, "Fenglong" （ST40） and "Tianshu" （ST25） for 20 min, once a day, 5 days a week for 6 weeks. Rats of the blank control and model groups were also restrained for 20 min. The body mass and food intake were measured every week, and the Lee's index, epididymal fat, perirenal fat and brown adipose tissue were weighed. The contents of serum total cholesterol （TC）, triglyceride （TG）, high density lipoprotein cholesterol （HDL-C）, low density lipoprotein cholesterol （LDL-C） and norepinephrine （NE） were determined by ELISA. H.E. staining was used to observe the morphological changes of white and brown adipose tissue. The mRNA expression levels of mitochondrial uncoupling protein 1 （UCP1）, peroxisome proliferator activated receptor γ co-activator 1α （PGC-1α）, PR-domain protein 16 （PRDM16）, peroxisome proliferator activated receptor γ （PPARγ） and Nrg4 in the adipose tissue were detected by quantitative real time PCR, and the protein expression levels of Nrg4, AMPKα, Sirt1 and interleukin-6 （IL-6） in the white and brown adipose tissue were detected by Western blot. RESULTS: Compared with the blank control group, the body mass, food intake, the Lee's index, epididymal fat and perirenal fat mass, and serum TG, TC and LDL-C contents and the expression level of IL-6 protein were significantly increased （P<0.01, P<0.05, P<0.001）, and the brown adipose mass, serum HDL-C and NE contents, the expression levels of UCP1, PGC-1α, PRDM16, PPARγ and Nrg4 mRNAs, and the protein expression levels of AMPKα, Sirt1 and Nrg4 proteins in both white and brown adipose tissues were significantly decreased in the model group （P<0.01, P<0.05）. After EA intervention, the increased levels of body mass, food intake, Lee's index, epididymal fat and perirenal fat mass, serum TG, TC and LDL-C contents, and the expression of IL-6 protein, and the decreased levels of brown adipose mass, serum HDL-C and NE contents, expression levels of UCP1, PGC-1α, PRDM16, PPARγ and Nrg4 mRNAs, and those of AMPKα, Sirt1 and Nrg4 proteins in both white and brown adipose tissues were apparently reversed（P<0.05, P<0.01, P<0.001）. H.E. staining showed an increase of the volume and content of intracellular vacuoles of both white and brown adipose tissues, disordered arrangement of cells with vague boundary in the model group, which was relatively milder including a decrease of volume and content of vacuoles of both white and brown adipose, neat arrangement of cells with clear boundary. CONCLUSION: EA intervention can improve lipid metabolism and promote white adipose tissue browning in middle-aged and aged obese rats, which is possibly associated with its functions in activating AMPK/Sirt1 signaling pathway and up-regulating the level of Nrg4.

Modeling Syphilis and HIV Coinfection: A Case Study in the USA.

Syphilis and HIV infections form a dangerous combination. In this paper, we propose an epidemic model of HIV-syphilis coinfection. The model always has a unique disease-free equilibrium, which is stable when both reproduction numbers of syphilis and HIV are less than 1. If the reproduction number of syphilis (HIV) is greater than 1, there exists a unique boundary equilibrium of syphilis (HIV), which is locally stable if the invasion number of HIV (syphilis) is less than 1. Coexistence equilibrium exists and is stable when all reproduction numbers and invasion numbers are greater than 1. Using data of syphilis cases and HIV cases from the US, we estimated that both reproduction numbers for syphilis and HIV are slightly greater than 1, and the boundary equilibrium of syphilis is stable. In addition, we observed competition between the two diseases. Treatment for primary syphilis is more important in mitigating the transmission of syphilis. However, it might lead to increase of HIV cases. The results derived here could be adapted to other multi-disease scenarios in other regions.

Analysis of an environmental epidemic model based on voluntary vaccination policy.

With the worsening of the environment and the increasing international trade, indirect transmission from exposure to contaminants in the surrounding environment has become an overlooked mode of transmission. This paper proposes a new game-theoretic model considering voluntary vaccination against imperfection and the unique integration of human-to-human and virus-to-human transmission routes. Based on the individual-based risk assessment update rule (IB-RA), the strategy-based risk assessment update rule (SB-RA), and the direct commitment update rule (DC), the different effects of individuals' behaviors on disease prevalence are analyzed. To find the effect of indirect transmission on epidemic transmission, we compare our model with the traditional SVIR model. Finally, it can be seen that indirect transmission mechanisms will aggravate the spread of epidemics.

[Effect of mild moxibustion on vascular aging in senescence rats based on local MCP-1/MMP-2/TGF-ß1 pro-inflammatory signal loop].

OBJECTIVE: To observe the effect of mild moxibustion on monocyte chemotaxis protein 1 (MCP-1)/matrix metalloproteinase 2 (MMP-2)/transforming growth factor ß1 (TGF-ß1) pro-inflammatory signal loop in senile rats, so as to explore its mechanisms underlying improving vascular aging (VA). METHODS: Twenty-four male VA SD rats were randomized into senium (VA) control, medication and moxibustion groups, and other 8 young SD rats (aged 2 months) were used as the young control group. The VA model was established by intraperitoneal injection of D-galactose (300 mg·kg-1·d-1) once daily for 4 weeks, and verified by serum total testosterone (TT) and free testosterone (FT) levels. For rats of the moxibustion group, mild moxibustion was applied to bilateral "Shenshu"(BL23) and "Guanyuan"(CV4) for 20 min, once a day, 5 days a week for 8 weeks. Rats of the medication group were treated by intraperitoneal injection of testosterone propionate (7 mg·kg-1·[3 d]-1) once daily for 8 weeks except weekends, and rats of the senium control and young control groups treated by intraperitoneal injection of the same dose of normal saline, once daily for 8 weeks except weekends. The duration of exhausted swimming (DES) before and after the treatment was recorded. H.E. staining and Masson staining were used to observe histopathological changes and collagen fiber content of the thoracic aortic tissue, respectively. The contents of serum TT, FT and angiotensin 2 (Ang Ⅱ) were determined by ELISA. The immunoactivity of aortic MCP-1 was detected by immunohistochemistry, and the expression levels of aortic MCP-1, MMP-2 and TGF-ß1 were detected by Western blot. RESULTS: Compared with the young control group, the levels of DES, serum TT and FT contents were significantly decreased (P<0.01), while those of serum AngⅡ and collagen fiber contents, aortic MCP-1 immunoactivity and MMP-2, TGF-ß1 and MCP-1 protein expression considerably increased in the senium control group (P<0.01). After the interventions, the decreased levels of DES, serum TT and FT contents and the increased levels of serum AngⅡ, collagen fiber contents, aortic MCP-1 immunoactivity and MMP-2, TGF-ß1 and MCP-1 protein expression were reversed in both medication and moxibustion groups (P<0.01, P<0.05). The therapeutic effect of mild moxibustion was significantly superior to that of medication in down-regulating the aortic collagen fiber, serum AngⅡ contents and MCP-1 immunoactivity and protein expression (P<0.05). H.E. staining showed thickened endometrium and disordered arrangement of vascular smooth muscles of the aorta in the senium group, and thinner endometrium and regular and ordered arrangement of aortic vascular smooth muscles in both moxibustion and medication groups. CONCLUSION: Mild moxibustion may improve vascular aging in senescence rats, which is possibly by suppressing vascular MCP-1/MMP-2/TGF-ß1 pro-inflammatory signal loop.

Using an age-structured COVID-19 epidemic model and data to model virulence evolution in Wuhan, China.

COVID-19 is a disease caused by infection with the virus 2019-nCoV, a single-stranded RNA virus. During the infection and transmission processes, the virus evolves and mutates rapidly, though the disease has been quickly controlled in Wuhan by 'Fangcang' hospitals. To model the virulence evolution, in this paper, we formulate a new age structured epidemic model. Under the tradeoff hypothesis, two special scenarios are used to study the virulence evolution by theoretical analysis and numerical simulations. Results show that, before 'Fangcang' hospitals, two scenarios are both consistent with the data. After 'Fangcang' hospitals, Scenario I rather than Scenario II is consistent with the data. It is concluded that the transmission pattern of COVID-19 in Wuhan obey Scenario I rather than Scenario II. Theoretical analysis show that, in Scenario I, shortening the value of L (diagnosis period) can result in an enormous selective pressure on the evolution of 2019-nCoV.

Modeling and Research on an Immuno-Epidemiological Coupled System with Coinfection.

In this paper, a two-strain model with coinfection that links immunological and epidemiological dynamics across scales is formulated. On the with-in host scale, the two strains eliminate each other with the strain having the larger immunological reproduction number persisting. However, on the population scale coinfection is a common occurrence. Individuals infected with strain one can become coinfected with strain two and similarly for individuals originally infected with strain two. The immunological reproduction numbers [Formula: see text], the epidemiological reproduction numbers [Formula: see text] and invasion reproduction numbers [Formula: see text] are computed. Besides the disease-free equilibrium, there are strain one and strain two dominance equilibria. The disease-free equilibrium is locally asymptotically stable when the epidemiological reproduction numbers [Formula: see text] are smaller than one. In addition, each strain dominance equilibrium is locally asymptotically stable if the corresponding epidemiological reproduction number is larger than one and the invasion reproduction number of the other strain is smaller than one. The coexistence equilibrium exists when all the reproduction numbers are greater than one. Simulations suggest that when both invasion reproduction numbers are smaller than one, bistability occurs with one of the strains persisting or the other, depending on initial conditions.

Modeling and optimal control analysis of COVID-19: Case studies from Italy and Spain.

Coronavirus disease 2019 (COVID-19) is a viral disease which is declared as a pandemic by WHO. This disease is posing a global threat, and almost every country in the world is now affected by this disease. Currently, there is no vaccine for this disease, and because of this, containing COVID-19 is not an easy task. It is noticed that elderly people got severely affected by this disease specially in Europe. In the present paper, we propose and analyze a mathematical model for COVID-19 virus transmission by dividing whole population in old and young groups. We find disease-free equilibrium and the basic reproduction number (R 0). We estimate the parameter corresponding to rate of transmission and rate of detection of COVID-19 using real data from Italy and Spain by least square method. We also perform sensitivity analysis to identify the key parameters which influence the basic reproduction number and hence regulate the transmission dynamics of COVID-19. Finally, we extend our proposed model to optimal control problem to explore the best cost-effective and time-dependent control strategies that can reduce the number of infectives in a specified interval of time.

Coinfection dynamics of heroin transmission and HIV infection in a single population.

We propose a model of a joint spread of heroin use and HIV infection. The unique disease-free equilibrium always exists and it is stable if the basic reproduction numbers of heroin use and HIV infection are both less than 1. The semi-trivial equilibrium of HIV infection (heroin use) exists if the basic reproduction number of HIV infection (heroin use) is larger than 1 and it is locally stable if and only if the invasion number of heroin use (HIV infection) is less than 1. When both semi-trivial equilibria lose their stability, a coexistence equilibrium occurs, which may not be unique. We compare the model to US data on heroin use and HIV transmission. We conclude that the two diseases in the US are in a coexistence regime. Elasticities of the invasion numbers suggest two foci for control measures: targeting the drug abuse epidemic and reducing HIV risk in drug-users.

[Electroacupuncture intervention increases testosterone level of aged rats by activating ERK/Nrf2/HO-1 signaling of Leydig cells].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on anti-oxidant function of Leydig cells in aged rats with low testosterone, so as to reveal its underlying mechanism of anti-aging of male reproduction. METHODS: Eighteen 20 months old SD rats were divided into aged control, medication and EA groups(n=6 in each group), and other 6 young male SD rats (2 months of age) were used as the youth control group. The rats of the youth and the aged control groups received subcutaneous injection of 0.9% normal saline (7 mg·kg-1·3 d-1) for 8 weeks, and those of the medication group received abdominal subcutaneous injection of Testosterone Propionate (7 mg·kg-1·3 d-1) for 8 weeks. EA (2 Hz/100 Hz, 1 mA) was applied to bilateral "Shenshu" (BL23) and "Guanyuan" (CV4) for 15 min, once daily for 8 weeks except the weekends. The levels of serum total testosterone (TT) and free testosterone (FT) were determined by enzyme linked immune sorbent assay (ELISA), the immunoactivity of phosphorylated extracellular signal-regulated protein kinase (p-ERK) was detected by immunohistochemistry, and the expression levels of ERK, p-ERK, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins in the testis tissues were determined by Western blot. RESULTS: Before and after the treatment, the levels of serum TT and FT in the aged control group were significantly lower than those of the youth control group (P<0.01). After the treatment, the serum TT and FT contents in the EA and medication groups were obviously higher than those in the aged control group (P<0.01). Compared with the youth control group, the expression levels of ERK, p-ERK, Nrf2 and HO-1 proteins were significantly down-regulated in the aged control group (P<0.01), while in comparison with the aged control group, the expression levels of ERK, p-ERK, Nrf2 and HO-1 proteins were significantly up-regulated in the medication and EA groups (P<0.01). The therapeutic effect of EA was notably superior to that of medication in up-regulating the immunoactivity of p-ERK, and the expression levels of ERK, p-ERK, Nrf2 and HO-1 proteins (P<0.01). No significant differences were found between the EA and medication groups in the increased levels of serum TT and FT after the intervention (P>0.05). CONCLUSION: EA intervention may increase testosterone level of the aged rats, which may be related to its effects in triggering ERK /Nrf2 /HO-1 signaling (anti-oxidative stress signal pathway) in the testis.

[Effects of Electroacupuncture and Intracerebral Injection of VEGF on Caspase12, Caspase3, and GRP78 Genes in Rats with Cerebral Ischemia-Reperfusion Injury].

OBJECTIVE: To determine the effects of electroacupuncture (EA) and intracerebral injection of vascular endothelial growth factor (VEGF) on caspase12, caspase3, and glucose regulated protein 78 kD (GRP78) genes of rats with cerebral ischemia reperfusion injury. METHODS: 60 SD rats were randomly divided into sham-operation group, model group, EA group and EA+VEGF group with 15 rats in each group. Middle cerebral artery occlusion (MCAO) method was used to establish the model of cerebral ischemia reperfusion injury. Electro-acupuncture intervention was introduced 1 day after the injury in the EA group and EA+VEGF group: 30 minutes each session and once a day for a total of 14 d [acupoint selection: Baihui (GV 20), Quchi(Li 11), Zusanli (ST36)]. The rats in the EA+VEGF group were also injected with 10 µL of VEGF165 (0.025 µg/µL) into the lateral ventricle after the first session of EA. Five rats in each group were sacrificed after obtaining a neurological function score (mNSS) at day 0 (1 d after modeling, before EA intervention), day 7 and day 14, respectively. Nissl staining was used to observe the histomorphology of cerebral infarction areas. Immunohistochemistry was used to CM(155mm]detect GRP78 activity in the ischemic brain tissues. Real-time fluorescence quantitative PCR (real-time PCR) was used to detect the expressions of caspase12, caspase3 and GRP78 mRNA in the ischemic brain tissues. RESULTS: Compared with the sham-operation group, rats in the model group had higher mNSS scores ( P<0.05), showed signs of cerebral infarction (with reduced numbers of and disordered Nissl bodies and unclear structure), increased GRP78 immunopositive cells, increased expression of GRP78 mRNA ( P<0.05), and increased expressions of caspase12 and caspase3 mRNA ( P<0.05). Compared with the model group, EA and EA+VEGF decreased mNSS scores at day 7 and 14 ( P<0.05), showing alleviated signs of cerebral infarction, increased GRP78 immunopositive cells ( P<0.05), increased GRP78 mRNA expression ( P<0.05), and decreased caspase12 and caspase3 mRNA expressions ( P<0.05). The most obvious changes were found in the EA+VEGF group ( P<0.05). No significant changes were observed in the sham-operation group over time ( P<0.05). In comparison, mNSS scores, the signs of cerebral infarction, and the expressions of caspase12 and caspase3 decreased over time in the other groups ( P<0.05), accompanied with increased GRP78 immunopositive cells and the expression of GRP78 gene ( P<0.05). CONCLUSION: Electroacupuncture and intracerebral injection of VEGF promote tissue repair of rats with cerebral ischemic injury, possibly through down-regulating the expressions of caspase12 and caspase3 genes and up-regulating the expression of GRP78 gene. The effect of electroacupuncture in combination with intracerebral injection of VEGF is superior to that of the single use of electroacupuncture.

[Warm needle moxibustion, mild moxibustion and electroacupuncture interventions have an anti-aging effect possibly by regulating hypothalamus-pituitary-testis axis in aged male rats].

OBJECTIVE: To observe the effect of warm needle moxibustion (WNM), mild moxibustion and electroacupuncture (EA) of "Shenshu" (BL23) and "Guanyuan" (CV4) on serum gonadal hormone levels and related gene expression in the hypothalamus and testis in aged rats, so as to explore their underlying mechanisms in anti-aging. METHODS: Forty male SD male rats were randomly divided into aged control, WNM, mild moxibustion, EA and medication groups (n ＝ 8 in each group), and other 8 male young adult SD rats were used as the youth control group. WNM (acupuncture plus moxibustion), mild moxibustion or EA (2 Hz /100 Hz, 1 mA) was separately applied to CV4 and bilateral BL23 for 15 min, once daily, 5 days a week for 8 weeks. Rats of the medication group received subcutaneous injection of testosterone propionate injection (7 mg/kg), once every 3 days, and those of the aged and youth groups received the same dose of 0.9% NaCl solution for 8 weeks. The levels of serum testoste-rone (T) and gonadotropin-releasing hormone (GnRH) were measured by ELISA. The expression of Kisspeptin (KISS-1), G protein-coupled receptors 54 (GPR54), RFamide-related peptide-3 (RFRP-3) and GPR147 mRNAs in the hypothalamus and GnRH-R, GPR54 and GPR147 mRNAs in the testis tissues were detected by quantitative real-time PCR. RESULTS: The levels of serum T and GnRH, and the expressions of KISS-1, GPR54, RFRP-3 and GPR147 mRNAs in the hypothalamus and GnRH-R and GPR54 mRNAs in the testis in the aged rats were significantly lower than those in the youth rats (P<0.05), while the expression level of GPR147 mRNA of the testis tissue was obviously higher in the aged group than that in the youth group (P<0.05). Follo-wing the treatment, the lowered serum T and GnRH contents, the down-regulated expression levels of hypothalamic KISS-1, GPR54, RFRP-3 and GPR147 mRNAs and testicle GnRH-R and GPR54 mRNAs, as well as the up-regulated testicle GPR147 mRNA expression in the aged rats were reversed in the WNM, mild moxibustion and EA groups (not the medication group except serum T) in comparison with the aged control group (P<0.05). The therapeutic effects of WNM, mild moxibustion and EA were significantly superior to those of medication in up-regulating serum GnRH content and expression levels of KISS-1, GPR54, RFRP-3 and GPR147 mRNAs in the hypothalamus and GnRH-R, GPR54 and GPR147 mRNAs in the testis (P<0.05). No significant differences were found among the WNM, mild moxibustion and EA groups in serum T and GnRH contents, and the expression levels of KISS-1, GPR54, RFRP-3 and GPR147 mRNAs in the hypothalamus and GnRH-R and GPR54 and GPR147 mRNAs in the testis (P>0.05)．. CONCLUSION: The WNM, mild moxibustion and EA therapies have an anti-aging effect by increasing serum T and GnRH levels in aged rats, which is possibly related to their effects in up-regulating the expression of hypothalamic KISS-1, GPR54, RFRP-3 and GPR147 mRNAs and testicle GnRH-R and GPR54 mRNAs, as well as down-regulating testicle GPR147 mRNA expression. The therapeutic effect of WNM, mild moxibustion and EA is evidently superior to that of medication.

[Electroacupuncture Combined with Intracerebral Injection of VEGF Improves Neurological Dysfunction Possibly by Down-regulating Expression of Endoplasmic Reticulum Stress Related Proteins ATF 6, etc. in Cerebral Ischemia-reperfusion Injury Rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) and EA combined with intracerebral injection of vascular endothelial growth factor (VEGF) on endoplasmic reticulum stress (ERS) related proteins and genes as activating transcription factor (ATF 6), inositol requiring enzyme-1 (IRE 1), CCAAT/enhancer binding protein homologous protein (CHOP), X box-binding protein-1 (XBP 1) of cerebral ischemia reperfusion injury (CIRI) rats, so as to study its repair effect for CIRI. METHODS: Forty male SD rats were equally and randomly divided into 5 groups: sham operation, model, EA, VEGF and EA+VEGF groups (n=8). The CIRI model was established by occlusion of the middle cerebral artery (MCAO) with thread embolism method. For rats of the sham operation group, the right common carotid artery was isolated without MCAO. EA (2 Hz/100 Hz, 1-3 mA) was applied to "Baihui" (GV 20), left "Quchi" (LI 11) and left "Zusanli" (ST 36) for 30 min, once a day for 14 days. For rats of the VEGF and EA+VEGF groups, 10 µL VEGF (0.025 µg/µL) was injected into the lateral ventricle 24 h after successful modeling. The rats' neurological function was assessed by using the modified neurological severity score (mNSS), and the histopathological changes of cerebral tissue were observed by Nissl staining method. The expression levels of ERS related proteins and genes ATF 6, IRE 1, XBP 1 and CHOP were determined by western blot (WB) and fluorescent quantitative PCR, separately. RESULTS: After modeling, the level of mNSS was significantly higher in the model group than in the sham operation group (P<0.05), and the number of Nissl bodies was markedly lower in the model group than in the sham operation group (P<0.05). Following the treatment, the mNSS was significantly lower in the EA, VEGF and EA+VEGF groups than in the model group (P<0.05), and the numbers of Nissl bodies were obviously higher in the EA, VEGF and EA+VEGF groups than in the model group (P<0.05), suggesting an improvement of neurological dysfunction and a repair of the injured cerebral tissue after the treatment. The levels of CIRI-induced increase of mNSS and CIRI-induced decrease of the number of Nissl bodies in the EA+VEGF group were respectively remarkably lower or higher than those of the simple EA and simple VEGF groups (P<0.05). WB and PCR showed that the expression levels of ATF 6, IRE 1, XBP1 and CHOP proteins and genes were notably higher in the model group than in the sham operation group (P<0.05), and considerably lower in the EA, VEGF and EA+VEGF groups than in the model group (P<0.05). Comparison among the three treatment groups showed that after the treatment, the expression levels of ATF 6, IRE 1, XBP1 and CHOP proteins and genes were obviously lower in the EA+VEGF group than in the EA and VEGF groups (P<0.05). CONCLUSION: EA and EA plus intracerebral microinjection of VEGF can improve neurological function and promote cerebral tissue repair in CIRI rats, which is associated with their effects in down-regulating the expression of ERS related proteins ATF 6, IRE 1, XBP1 and CHOP. The effect of EA+VEGF is superior to that of simple EA and simple VEGF.

[ASL-based Observation of Central Nervous System Responses to Acupuncture Analgesia for People with Different Sensitivities].

OBJECTIVE: To examine the effects of different sensitivities on the effectiveness of acupuncture analgesia by observing activation change characteristics of cerebral areas resulting from the influences of constitutions on analgesia effects and to discuss the response mechanism of central nervous system (CNS) to determine the factor of constitutions on acupuncture efficacy using cerebral functional magnetic resonance imaging arterial spin labeling (fMRI-ASL). METHODS: Participants with different sensitivities were assessed according to standard screening and grouped into two groups: insensitivity group (n＝24) and sensitivity group (n＝22). All participants were given acupuncture at the left-sided Zusanli point. Pressure pain threshold (PPT) of their body surface was determined before and after the acupuncture, and the two groups were subsequently compared in terms of analgesic effects and PPT rate of change; cerebral fMRI-ASL was performed; software such as SPM 8 and ASLtbx were utilized to preprocess the results, and correlation between regional cerebral blood flow (rCBF) and visual analog scale (VAS) score was determined using Pearson's correlational analysis. RESULTS: VAS score in the sensitivity group was significantly higher than that in the insensitivity group (P< 0.05); after acupuncture, PPT rate of change in the sensitivity group was higher than that in the insensitivity group (P< 0.05). The analyses revealed that there was a negative correlation between rCBF and VAS score for the right-sided anterior cingulate cortex in the insensitivity group and superior frontal gyrus in the sensitivity group (|r|>0.3 and P<0.05). CONCLUSION: Different sensitivity to acupuncture is one of the crucial factors influencing analgesia effects. The sensitivity group had superior analgesia effect than the insensitivity group. Acupuncture might deactivate cerebral functional areas to generate analgesic effects.The superior frontal gyrus and bilateral anterior cingulate cortex, because of deactivation, play a positive role in sensitive patients, which is probably one of the CNS cerebral areas responding to acupuncture analgesia of people who are sensitive to acupuncture.

[Electroacupuncture Intervention Improves Physical Power of Aged Rats with Low Testosterone by Reducing Chronic Inflammatory Response of Leydig Cells].

OBJECTIVE: To assess the effect of electroacupuncture (EA) on chronic inflammatory response of Leydig cells in aged rats with low testosterone, so as to investigate its underlying mechanism of anti-male reproductive aging. METHODS: Twenty-four 20 months old SD rats were randomly divided into EA, medication and aged control groups (n＝ 8 in each), and other 8 young SD rats (2 months of age) were used as the youth control group. EA (2 Hz/100 Hz, 1 mA) was applied to "Guanyuan"(CV 4) and bilate-ral "Shenshu"(BL 23) for 15 min, once daily for 8 weeks except the weekends. The medication group received abdominal subcutaneous injection of testosterone propionate (7 mg• kg－1• 3 d－1) for 8 weeks. The aged control group and the youth control group received subcutaneous injection of 0.9% normal saline, with the same dose and same treatment frequency as those of the medication group. The rats' physical power was assessed according to the exhausted swimming duration, and the levels of serum total testosterone (TT) and free testosterone(FT) were determined by ELISA. The pathological changes of the testis tissue were detected by using H．E.staining, and the immunoactivity of cyclooxygenase-2 (COX-2) in Leydig cells was detected by immunohisto-chemistry. The expression levels of nuclear factor-κB p 65 (NF-κB p 65), COX-2, interleukin-1 ß (IL-1 ß) and tumor necrosis factor-α (TNF-α) proteins in the testis tissues were determined by Western blot. RESULTS: Before and after treatment, the exhaustive swimming duration and the levels of serum TT and FT in the aged control group were significantly lower than those of the youth control group (P < 0.01). After the treatment, the exhaustive swimming duration and serum TT and FT in the EA and medication groups were notably higher than those in the aged control group (P<0.01). HE staining showed that the incompleteness of basement membrane of spermatogenic tubules, reduction of spermatogenic cells and supporting cells and irregularity of Leydig cells in the testis tissue of the aged rats were relatively milder after EA intervention. Compared with the youth control group, the expression levels of NF-κB p 65 and COX-2, IL-1 ß and TNF-α in the testicular tissue were significantly higher in the aged control group (P<0.01),while in compared with the aged control group, the expression levels of NF-κB p 65, COX-2, IL-1 ß and TNF-α proteins were significantly down-regulated in the EA group (P<0.01). CONCLUSION: EA intervention can improve the physical power of the aged rats with low testosterone, which may be related to its effects in up-regulating TT and FT levels, and in reducing chronic inflammatory response in the testis tissue.

Dynamics of an age-structured heroin transmission model with vaccination and treatment.

Based on the development of heroin vaccine, in this paper, we propose an age structured heroin transmission model with treatment and vaccination. The model allows the drug reuse rate of the individuals in treatment to depend on a treatment-age and the vaccine waning rate of the vaccinated to depend on a vaccination age. Meanwhile, the model allows that the heroin vaccine provides an imperfect protection (i.e., the vaccinated individuals can also become drug addicted). We derive the basic reproduction number which dependents on vaccination. The basic reproduction number completely determines the persistence and extinction of heroin spread, i.e., if the basic reproduction number is less than one the drug-free steady state is globally asymptotically stable (i.e., the heroin spread dies out), if the basic reproduction number is larger than one, there exists an unique positive steady state and it is locally and globally stable in some special cases. Finally, some numerical simulations are carried out to illustrate the stability of the positive steady state.

Global dynamics of a vector-host epidemic model with age of infection.

In this paper, a partial differential equation (PDE) model is proposed to explore the transmission dynamics of vector-borne diseases. The model includes both incubation age of the exposed hosts and infection age of the infectious hosts which describe incubation-age dependent removal rates in the latent period and the variable infectiousness in the infectious period, respectively. The reproductive number R0 is derived. By using the method of Lyapunov function, the global dynamics of the PDE model is further established, and the results show that the basic reproduction number R0 determines the transmission dynamics of vector-borne diseases: the disease-free equilibrium is globally asymptotically stable if R0 ≤ 1, and the endemic equilibrium is globally asymptotically stable if R0 > 1. The results suggest that an effective strategy to contain vector-borne diseases is decreasing the basic reproduction number R0 below one.

Global properties of vector-host disease models with time delays.

Since there exist extrinsic and intrinsic incubation periods of pathogens in the feedback interactions between the vectors and hosts, it is necessary to consider the incubation delays in vector-host disease transmission dynamics. In this paper, we propose vector-host disease models with two time delays, one describing the incubation period in the vector population and another representing the incubation period in the host population. Both distributed and discrete delays are used. By constructing suitable Liapunov functions, we obtain sufficient conditions for the global stability of the endemic equilibria of these models. The analytic results reveal that the global dynamics of such vector-host disease models with time delays are completely determined by the basic reproduction number. Some specific cases with discrete delay are studied and the corresponding results are improved.

Competitive exclusion in a multi-strain immuno-epidemiological influenza model with environmental transmission.

In this paper, a multi-strain model that links immunological and epidemiological dynamics across scales is formulated. On the within-host scale, the n strains eliminate each other with the strain having the largest immunological reproduction number persisting. However, on the population scale, we extend the competitive exclusion principle to a multi-strain model of SI-type for the dynamics of highly pathogenic flu in poultry that incorporates both the infection age of infectious individuals and biological age of pathogen in the environment. The two models are linked through the age-since-infection structure of the epidemiological variables. In addition the between-host transmission rate, the shedding rate of individuals infected by strain j and the disease-induced death rate depend on the within-host viral load. The immunological reproduction numbers [Formula: see text] and the epidemiological reproduction numbers [Formula: see text] are computed. By constructing a suitable Lyapunov function, the global stability of the infection-free equilibrium in the system is obtained if all reproduction numbers are smaller or equal to one. If [Formula: see text], the reproduction number of strain j is larger than one, then a single-strain equilibrium, corresponding to strain j exists. This single-strain equilibrium is globally stable whenever [Formula: see text] and [Formula: see text] is the unique maximal reproduction number and all of the reproduction numbers are distinct. That is, the strain with the maximal basic reproduction number competitively excludes all other strains.

[Effect of eletroacupuncture with close-to-bone needling treatment on expression of Sox9, VEGF and ColX in impaired cartilage of rabbits with knee osteoarthritis].

OBJECTIVE: To investigate the effect of eletroacupuncture with close-to-bone needling treatment on expression of Sox9, vascular endothelial growth factor (VEGF) and type X collagen (ColX) in impaired cartilage of rabbits with knee osteoarthritis (KOA) and explore its possible mechanisms. METHODS: Forty New Zealand rabbits were randomized equally into normal control group, KOA model group, eletroacupuncture with close-to-bone needling group (CN group), and normal thrust needing group (NTN group). In the latter 3 groups, KOA was induced by Hulth-Telhag treatment and evaluated with X-ray examination, and 6 weeks after the modeling, eletroacupuncture for 20 min was administered in CN and NTN groups at the acupoints "Zusanli", "Waixiyan", "Neixiyan", "Liangqiu" and "Yinlingquan" in the left knee joints once daily for 5 days as a treatment cycle. After 5 treatment cycles, the rabbits were examined for behavioral changes, cartilage morphology, and Mankin scores; The protein and mRNA expressions of S0x9, VEGF, and ColX were examined using Westen blotting, immunohistochemistry, and RT-PCR as appropriate. RESULTS: The rabbits in the model, CN and NTN groups showed significant changes in behaviors and cartilage histomorphology after the modeling and after the treatments. HE staining showed that cartilage injury was repaired and tended to recovery in CN and NTN groups. The cartilage pathologies was severer in the model group than in the normal control, CN and NTN groups (P<0.01); Sox9 protein increased and VEGF mRNA level decreased in CN and NTN groups after treatment as compared with those in the model group (P<0.01). CONCLUSION: Eletroacupuncture with close-to-bone needling can effectively improve KOA in rabbits probably by enhancing Sox9 and reducing VEGF and ColX expressions in the cartilage to inhibit hypertrophic differentiation of the chondrocytes, maintain chondrogenic phenotype and repair cartilage cells.

[Effect of Electro-acupuncture on the Expression of Slit2 and HSPGs in Rats with Focal Cerebral Infarction].

OBJECTIVE: To determine the expression of Slit2 and heparan sulfate proteoglycans (HSPGs) in cortex of rats with focal cerebral infarction and the effect of acupuncture (EA) on the expression of Slit2 and HSPGs. METHODS: 40 male Sprague Dawley (SD) rats were equally randomized into four groups: Control group, model group, non-acupoint EA group, and EA group. Thread-tying method was used in the model group, non-acupoint EA group and EA group to clog arteries and then open up after 1.5 h. Morphology changes of tissues around the infarction area were observed 14 days later by Nissl staining. The expressions of Slit2 and HSPGs in the ischemic brain tissues were detected by indirect immunofluorescence staining (IF) and Western blot (WB). RESULTS: Modified neurologicalseverity scores (mNSS) showed zero in the control group, lower than the score of EA group. The EA group had lower mNSS score than the non-acupoint group. The highest mNSS score appeared in the model group. Paired comparisons showed statistical differences (P < 0.01). Nissl's staining showed that EA group had increased Nissl bodies in alignment; non-acupoint EA group had increased and disordered Nissl bodies; model group had decreased and disordered Nissl bodies with edema in the brain. IF and WB showed that non-acupoint EA group had higher levels of Slit2 and HSPGs than model group (P < 0.05); EA group had higher levels of Slit2 and HSPGs than non-acupoint EA group (P < 0.05); model group had higher levels of Slit2 and HSPGs than control group (P < 0.05). The results of Nissl' s staining, IF and WB were consistent. CONCLUSION: EA can enhance the expressions of Slit2 and HSPGs. This may be one of the mechanisms of EA promoting recovery of neural functions after cerebral infarction.