Comparative effectiveness of Chinese herbal injections treating for rotavirus enteritis in children: A systematic review and Bayesian network meta-analysis.

Background: Rotavirus enteritis (RVE) accounts for 37% of all death in children (<5 years) with diarrhea. Chinese herbal injections (CHIs) have drawn more attention from practitioners because of the valid effects for RVE. However, the most beneficial one has not yet been determined. Methods: Eight databases were searched from their inception up to September 3rd, 2022. The primary outcome was clinical effective rate and the secondary outcomes were time for disappearance of diarrhea, time of defervescence, time for disappearance of vomiting, and adverse drug reactions or adverse drug events. OpenBUGS 3.2.3 and STATA 14.0 software were employed to carry out the NMA. Results: 58 randomized controlled trials (RCTs) with 6436 child patients were included in this Bayesian NMA. Four CHIs were investigated including Yanhuning injection (YHN), Xiyanping injection (XYP), Reduning injection (RDN), and Zedoary Turmeric Oil injection (ZTO). The results showed that YHN [OR=6.16, 95% CI (4.39, 8.77)] had a superior effect in improving clinical effective rate compared to Ribavirin based on Western medicine (WM). According to SUCRA values, YHN (84.1%) ranked highest. As for the secondary outcomes, XYP was the better intervention in shortening the time for disappearance of diarrhea. Regarding time for defervescence, RDN had obvious advantages and also performed well in time for disappearance of vomiting. Conclusion: CHIs combined with WM could be beneficial than Ribavirin in improving clinical effective rate, and YHN was the optimum treatment. From the comprehensive evaluations of both the clinical effective rate and other outcomes, YHN also indicated a favorable therapeutic effect in RVE. Study registration: PROSPERO, CRD42022357149.

[Pioglitazone ameliorates atherosclerosis in apoE knockout mice through transforming growth factor-ß/Smad signaling and adaptive T cell immunity].

OBJECTIVE: To examine whether transforming growth factor-ß (TGF-ß) pathway and adaptive T cell immunity play roles in the anti-atherosclerotic effects of pioglitazone (PIO) in ApoE-/- mice. METHODS: ApoE-/- mice with atherosclerosis induced by high-fat feeding were treated daily with PIO (20 mg/kg) or vehicle for 8 weeks. The protein expressions of TGF-ß pathway in the atheromatous lesions of the aorta and the percentages of IFN-γ+ and Foxp3+ cells in the spleen of the mice were examined with immunohistochemical staining. In the in vitro experiment, primary cultured splenocytes were stimulated with oxidized low-density lipoproteins (oxLDL) and treated with PIO either alone or in combination with the PPARγ antagonist GW9662, after which the changes in percentages of CD4+IFN-γ+ cells and CD4+CD25+Foxp3+ cells were analyzed with flow cytometry. RESULTS: PIO treatment of ApoE-/- mice with high-fat feeding significantly attenuated the progression of atheromatous lesions (P<0.05) and resulted in increased expressions of TGFß1 (P<0.01), TGFßRII (P<0.05), and p-Smad3 (P<0.05) and a decreased expression of Smad7 (P<0.05) in the lesions. PIO treatment also led to decreased percentage of IFN-γ+ cells (P<0.05) and increased percentage of Foxp3+ cells (P<0.01) in the spleen of the mice. In primary cultured splenocytes, PIO treatment caused significant down-regulation of IFN-γ mRNA (P<0.05) and up-regulation of Foxp3 mRNA (P<0.05) and obviously increased the percentages of CD4+IFN-γ+ cells (P<0.05) and CD4+CD25+Foxp3+ (P<0.05); the effects of PIO on CD4+IFN-γ+ and CD4+CD25+Foxp3+ cells were abolished by treatment of the cells with GW9662. CONCLUSION: The anti-atherosclerotic effect of PIO is probably mediated by the TGF-ß/Smad signaling pathway and PPAR-γ-dependent modulation of Th1/Treg population.

[Supplemental Fuzhenghuayu capsule therapy for improving liver fibrosis markers in patients with chronic hepatitis B following unsatisfactory outcome of nucleos(t)ide analogue monotherapy].

OBJECTIVE: To investigate the ability of Fuzhenghuayu capsule to improve markers of liver fibrosis when provided as supplemental therapy in patients with chronic hepatitis B (CHB) who achieved complete virological response but unsatisfactory resolution of fibrosis markers with nucleos(t)ide analog (NAs) monotherapy. METHODS: One-hundred-and-ten patients with CHB-related liver fibrosis who had received NA for more than or equal to 2 years and achieved sustained virological response (SVR) but no improvement in liver fibrosis index were randomly divided into two equal groups: experimental group, continued oral NAs (one tablet, 1 time/day) with simultaneous Fuzhenghuayu capsule (1.5 g, 3 times/day) for 48 weeks; control group, continued oral NAs only for 48 weeks. Serum fibrosis markers (hyaluronic acid (HA), laminin (LN), amino terminal propeptide of type III procollagen (PIIIP) and IV collagen (IV-C)), liver fibrosis stages, B ultrasonic wave, and liver function were observed before (baseline) and after treatment and compared by statistical analysis. RESULTS: The baseline levels of fibrosis markers were not significantly different between the experimental and control groups. After treatment, the levels of all of the fibrosis markers were lower in the experimental group (P less than 0.05 vs. control group; HA t = 19.548, LN t = 2.264, PIIIP t = 2.230, and IV-C t = 6.649) and lower than the baseline levels (P less than 0.01; HA t = 12.458, LN t = 7.402, PIIIP t = 4.620, IV-C t = 8.937). The control group also showed a significant reduction in HA and LN levels after treatment (P less than 0.01 vs. baseline; t = 5.202 and 3.444), but PIIIP and IV-C were unaffected. The baseline liver fibrosis stages were not significantly different between the experimental and control groups. After treatment, only the experimental group showed significant improvement in liver fibrosis stages (P less than 0.01). The rates of excellent therapeutic outcome, effectiveness, and non-effectiveness were significantly different between the experimental group (11.3%, 43.4%, and 45.3%) and the control group (1.0%, 22.2%, and 75.6%) (x2 = 9.408, P less than 0.01). Similar trends were observed for improvements in B ultrasonic wave for liver and spleen and in markers of liver function. Finally, neither treatment group experienced adverse effects. CONCLUSION: For CHB patients who achieve SVR by antiviral treatment with NAs, but unsatifactory improvement in liver fibrosis indices, administration of supplemental Fuzhenghuayu capsule with continued NAs therapy may represent a safe and effective treatment.

The interventional therapy for diabetic peripheral artery disease.

BACKGROUND: Diabetic peripheral arterial disease is the main cause of lower limb amputation in patients with diabetes. To summarize the technique and experiences and evaluate the clinical effects of blood vessel intervention operation on diabetic peripheral artery disease. METHODS: 81 patients with diabetic peripheral artery disease from October 2007 to September 2011, 81 cases of the observation group were treated by balloon PTA. By adopting the Seldinger puncture technology, intubation was placed into a cobra catheter or a pig tail artery catheter and directed to the ipsilateral lower extremity artery. A guidewire was used to reach the lesion part of patients and a long balloon with a diameter of 4-6 mm was used to expand the artery with a pressure of 6-10 atm. RESULTS: 81 patients in the observation group received the PTA surgery. The technical succesful rate was 100%, no complication happened. The skin temperature increased after treatment. The blood supply improved significantly. The pulsation of the foot dorsal artery was strengthened. The numbness and pain symptoms were moderated significantly. We observed better results in the observation group in lower limb vessel diameter and foot ulceration healing. None of the patients received amputation surgery. Its short-term effects were satisfactory. CONCLUSION: PTA is a feasible technique for diabetic peripheral artery disease. It has great clinical significance in treating diabetic peripheral arterial disease. Although its short-term effects is satisfactory, the long-term effects is necessary for follow up.

Multiple roles of SOCS proteins: differential expression of SOCS1 and SOCS3 in atherosclerosis.

Pro-inflammatory cytokines play a key pathogenic role in atherosclerosis, which are induced by the Janus kinase/signal transducer and activator of transduction (JAK/STAT) pathway. Furthermore, the JAK/STAT pathway is negatively regulated by the suppressor of cytokine signaling (SOCS) proteins. However, the change in SOCS expression levels and the correlation between SOCS expression and cholesterol levels in atherosclerosis is not yet well understood. To this end, a mouse model of atherosclerosis was established using apolipoprotein-deficient (ApoE(-/-)) mice. The mice were fed either a chow or high-fat diet. The mRNA and protein expression of SOCS1 and SOCS3 in plaque and vessels were determined at different time points. Furthermore, SOCS1 and SOCS3 mRNA expression was detected in the peripheral blood mononuclear cells (PBMCs) obtained from 18 male subjects with no coronary heart disease (non-CHD) population. The expression of SOCS1 in the ApoE(-/-) mice first increased and then decreased and the high-fat diet accelerated the appearance of the peak; the expression of SOCS3 increased with the increased feeding duration, and this trend was more pronounced in the mice fed the high-fat diet. SOCS1/CD68 and SOCS3/CD68 showed opposite trends in expression with the increased duration of the high-fat diet. Interleukin-6 (IL-6) expression in the main aorta of the ApoE(-/-) mice fed the high-fat diet also increased with the increased feeding duration. In the non-CHD population, the total serum cholesterol levels positively correlated with SOCS3 mRNA expression in the PBMCs (r=0.433, P=0.012). These results demonstrate the differential expression of SOCS1 and SOCS3 in atherosclerosis and suggest that SOCS3, together with IL-6 may promote the formation and development of atherosclerosis.

[Effects of the diet ratio of polyunsaturated fatty acids ω-3/ω-6 on experimental colitis in mice].

OBJECTIVE: To investigate the effect of changed ratio of polyunsaturated fatty acids (PUFA) on dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: Thirty-two male BALB/c mice were randomly divided into two groups: control group and PUFA group, PUFA group was continuously divided into 3 sub-groups: PUFA ω-3/ω-6 1:3 group, PUFA ω-3/ω-6 1:15 group and PUFA ω-3/ω-6 1:30 group. According to the difference in the sub-groups, PUFA group mice were fed with the corresponding modified diet. The control group was fed with the common diet, whose ratio of PUFA ω-3/ω-6 was 1:15. After eight weeks of different diets, experimental colitis in the three sub-groups of PUFA group was induced by DSS exposure. The mice were placed on three five-day cycles of 30 g/L DSS with ten days of recovery after each cycle, then were sacrificed after the final ten-day period. Overall symptomatic score and histopathological score were evaluated. And levels of mucosal prostaglandin E2 (PGE2) in the proximal and distal colon were measured respectively by enzyme immunoassay. RESULTS: The changed ratio of PUFA ω-3/ω-6 had no effect on the weight gain of the growing mice. Although there were no significant differences among the PUFA groups from the three separate aspects: weight gain, stool character and blood in the stool, there were significant differences among the three groups in overall symptomatic scores. A further comparison showed the overall symptomatic score of 1:3 group was significantly lower than that of the 1:30 group (P<0.05). There were significant differences among the PUFA groups in the histopathological score. The following comparison between the sub-groups showed the histopathological score of the 1:3 group was significantly lower than that of the 1:30 group (P<0.05). One mouse in the 1:30 group died of severe hemorrhage and one mouse also in this group had a huge dysplastic adenomatous polyp. The mucosal PGE2 which could reflect the level of intestinal inflammation showed that in the distal colon, the inflammations were obvious, and the levels of mucosal PGE2 of the distal colon in the 1:15 group [(153.0 ± 49.4) ng/g tissue] and the 1:30 group [(192.4 ± 94.0) ng/g tissue] were significantly higher than that of the control group [(43.2 ± 13.4) ng/g tissue, P<0.05], but there was no significant difference between the 1:3 group [(43.4 ± 8.2) ng/g tissue] and the control group. Although the mucosa damages were sparing in proximal colon, the level of mucosal PGE2 of the proximal colon in 1:30 group [(97.4 ± 64.8) ng/g tissue] markedly increased as compared with the control group [(21.6 ± 16.0) ng/g tissue, P<0.01], there were no differences among the 1:3 group [(36.6 ± 4.6) ng/g tissue], the 1:15 group [(18.8 ± 6.4) ng/g tissue] and the control group. CONCLUSION: The colonic inflammatory severity and the level of mucosal PGE2 in the experimental colitis mice were affected by the changed ratio of PUFA ω-3/ω-6 in the feed. Increased ratio of PUFA ω-3/ω-6 in the feed had a protective effect on the intestinal mucosa in the experimental colitis mice, otherwise had hazards. Before the inflammation happened, changed ratio of PUFA ω-3/ω-6 firstly altered the local inflammatory factors, such as PGE2, and then affected the inflammatory severity.

Coexpression of recombinant adenovirus carrying GDNF and EDNRB genes in neural stem cells in vitro.

Gene therapy and nerve stem cells isolated from the developing human enteric nervous system (ENS) are significant. They may open the route for the cell therapy of Hirschsprung's disease (HD). We have constructed the recombinant adenovirus-carrying glial cell line-derived neurotrophic factor (GDNF) and endothelin receptor B (EDNRB) gene, and investigated the exosomatic coexpression in neural stem cells. The recombinant adenovirus Ad-GE coexpressing GDNF and EDNRB gene was constructed by the AdEasy system and confirmed by the reverse transcription polymerase chain reaction (RT-PCR) method. Expression of exogenous genes in neural stem cells after transfection was confirmed by the flow cytometry and real-time fluorescence quantitative PCR. Fragments of pAd Track-CMV-GE were consistent with GDNF and EDNRB. The green fluorescence of the positive cells was followed by fluorescence microscopy at 24 h after NSCs had been transfected, reaching a peak at 72 h after transfection. Flow cytometry showed that the efficiency of transfection was 15.0, 23.6, and 25.4% at 24, 48 and 72 h respectively. Real-time fluorescence quantitative PCR showed the expression levels of mRNA of GDNF and EDNRB in 48 and 72 h groups were obviously higher than that in 24 and 96 h groups. Recombinant adenovirus carrying GDNF and EDNRB genes are coexpressed in neural stem cells, which may offer the possibility of a novel approach to local combination gene therapy for Hirschsprung's disease.

[Relationship between accelerated artherosclerosis and Treg/Teff balance in uremic apoE-/- mice].

OBJECTIVE: To establish a uremic apolipoprotein E knockout (apoE-/-) mouse model and explore the relationship between accelerated atherosclerosis and Treg/Teff balance. METHODS: Using apoE-/- mice with C57BL/6J background, uremic apoE-/- mice were created by electrocautery of the right kidney and nephrectomy of the left, and the control apoE-/- mice received a sham-operation. Two weeks after inducing uremia, the renal function of the mice were evaluated to assess the validity of the model. Ten weeks after the operation, blood samples were obtained from the mice to assess the renal function and serum total cholesterol (TCH); the serum concentrations of transforming growth factor-beta(1) (TGF-beta(1)) and interferon-gamma (IFN-gamma) were detected by ELISA, and CD4(+)CD25(+)Foxp3(+)Treg ratio in the spleen was determined by flow cytometry. RT-PCR was used to detect the expression of Foxp3 and IFN-gamma mRNA in the aorta, and oil red O staining used to investigate the relative atherosclerotic area on the frozen sections of the aortic root. The correlation between the renal function parameters and Treg quantity was analyzed. RESULTS: Renal function detection confirmed successful establishment of the uremic apoE-/- mouse model. Ten weeks after the operation, the relative atherosclerotic plaque area in the aortic root plaque increased significantly, the spleen Treg ratio decreased, the serum concentrations of TGF-beta(1) decreased and IFN-gamma and TCH increased, the expression of aortic Foxp3 mRNA decreased and IFN-gamma mRNA increased as compared with those in the control apoE-/- mice. A significant inverse correlation was found between the renal function parameters and Treg quantity in uremic apoE-/- mice. CONCLUSION: In uremic apoE-/- mice, accelerated aortic atherosclerosis is correlated to the T cell subset (Treg/Teff) imbalance shown by decreased quantity and impaired function of Treg and enhanced activity of Teff.

High glucose promotes intracellular lipid accumulation in vascular smooth muscle cells by impairing cholesterol influx and efflux balance.

AIMS: High glucose promotes macrophage-derived foam cell formation involved in increased influx or reduced efflux of lipids. The aim of this study is to investigate the influence of hyperglycaemia on foam cell transformation of vascular smooth muscle cells (VSMCs) and possible mechanisms contributing to these effects. METHODS AND RESULTS: The results showed that high glucose increased the expression of CD36, a regulator of lipid influx, and suppressed the expression and activity of the adenosine triphosphate-binding cassette (ABC) transporter ABCG1, a regulator of cholesterol efflux to high-density lipoprotein, in a dose- and time-dependent manner. However, cholesterol efflux to lipid-free apoAI was not impaired. VSMCs exposed to high glucose readily developed into lipid-loaded cells, as demonstrated by Oil Red O staining and cholesterol content analysis. In addition, high glucose-induced down-regulation of ABCG1 was reversed by nuclear factor-kappaB (NF-kappaB) inhibitors BAY 11-7085 and tosyl-phenylalanine chloromethyl ketone and by the antioxidant N-acetyl-L-cysteine (NAC). This reversal was accompanied by reduced cellular lipid content. Also, NAC and NF-kappaB inhibitors can effectively block the high glucose-induced activity of NF-kappaB binding to DNA and/or peroxide production. CONCLUSION: These results suggested that hyperglycaemia-induced foam cell formation in VSMCs was related to the imbalanced lipid flux by increasing CD36-mediated modified low-density lipoprotein uptake and reducing ABCG1-regulated cellular cholesterol efflux. Moreover, this effect was associated with increased oxidative stress and activated NF-kappaB pathway signalling.

[Bone marrow stem cell mobilization to the peripheral blood and tumor necrosis factor-alpha expression in ischemic myocardium in rabbit models of hibernating myocardium].

OBJECTIVE: To investigate the changes in peripheral blood bone marrow stem cells and tumor necrosis factor-alpha gene expression in the ischemic myocardium in rabbit models of hibernating myocardium. METHODS: Twenty-four male Japanese white rabbits were randomized into 4 groups, including a sham-operated group and 3 model groups with hibernating myocardium induced by partial ligation of the left anterior descending coronary artery. The percentage of CD34-positive cells in the peripheral blood was evaluated by flow cytometry, and TNF-alpha mRNA expression in the ischemic myocardium was determined by real-time RT-PCR in the 3 model groups (at 3, 7, or 28 days after the operation) and in the sham-operated group. RESULTS: In rabbits with partial ligation of the left anterior descending coronary artery, the percentage of CD34-positive cells in the peripheral blood and myocardial TNF-alpha mRNA expression were significantly increased at 3 and 7 days after the operation in comparison with those in the sham-operated group and those at 28 days postoperatively (P<0.01). No significant differences were found in the percentage of CD34 positive cells or myocardial TNF-alpha mRNA expression between the sham-operated group and the rabbits 28 days after the coronary artery ligation (P>0.05). CONCLUSION: Bone marrow stem cell can be mobilized into the peripheral blood in rabbit hibernating myocardium model possibly by increasing TNF-alpha gene expression in the ischemic myocardium.

[The relationship between alpha-IFN anti-virus treatment and HLA-DRB1*11 gene mononucleotide polymorphism].

OBJECTIVE: To investigate the relationship between the distribution of mononucleotide polymorphism of five regulation regions of alpha-IFN among HLA-DRB1*11 gene episodes and the therapeutic effects of alpha-IFN treatment in chronic hepatitis B patients. METHODS: One hundred seven chronic hepatitis patients from Nanjing Second Hospital who were treated by alpha-IFN for 12 months and then followed at least six months without the treatment were randomly selected for this regressive analysis. They were grouped into a continuous responsive group and a non-continuous responsive group. Hepatitis B virus X interacting protein gene locus was searched in NCBI. Single nucleotide polymorphism (SNP) gene locus was detected based on a pooling sequencing method. Primer and TaqMan-MGB probes referring to different mononucleotide loci were designed respectively to detect SNP in five regulation regions of alpha-IFN. Then gene sequencing differences between the two groups were analyzed. RESULTS: Among the 107 cases there were 30 cases (28.0%) in the continuous responsive group and 77 cases (71.9%) in the non-continuous responsive group. CT occupation rate in five regulation regions of IFN reached 18.0% in the continuous responsive group and 23.8% in the non-continuous responsive group. AG occupation rate reached 10.8% in the former group and 15.8% in the latter group. The differences in CT and AG between the two groups were significant. CONCLUSIONS: The distribution of mononucleotide polymorphism of five regulation regions of alpha-IFN among HLA-DRB1*11 gene episodes affects the IFN anti-virus treatment. Detecting the gene distribution of mononucleotide in five regulation regions of alpha-IFN helps in predicting the therapeutic effects of alpha-IFN.

Electrophysiological evidence for the interaction of substance P and glutamate on Adelta and C afferent fibre activity in rat hairy skin.

1. The purpose of the present study was to investigate whether there was a cooperative interaction between substance P (SP) and glutamate (GLU) administered subcutaneously on Adelta and C primary afferent fibre activity in dorsal hairy skin of the rat in vivo. The single unit activities of Adelta and C afferent fibres were recorded by isolation of fibre filaments from the dorsal cutaneous nerve branches and the effects of subcutaneous injections of low doses of SP, GLU and SP + GLU on activity were determined. 2. Sub-threshold doses of SP (1 micro mol/L, 10 microL) administered subcutaneously into the dorsal hairy skin had no effect on the afferent discharges of either Adelta or C units. 3. The afferent discharges of 35% (11/31) of Adelta fibres and 33% (6/18) of C fibres were increased by local injection of the submaximal doses of GLU (10 micro mol/L, 10 microL) into the receptive fields. 4. The GLU-induced excitatory response was significantly enhanced by coinjection of subthreshold doses of SP. The mean discharge rates of Adelta fibres and C fibres were increased from 5.84 +/- 1.54 and 5.02 +/- 2.65 impulses/min to 19.91 +/- 4.35 and 17.58 +/- 5.59 impulses/min, respectively, whereas the excitatory proportions of Adelta and C fibres were increased from 35 and 33% to 84 and 83%, respectively. The duration of the excitation for Adelta fibres and C fibres was also significantly increased after coinjection of SP + GLU compared with that observed when either substance was given alone. 5. The present study provides electrophysiological evidence for an interaction between receptors for SP and GLU on the fine fibres activities in rat hairy skin, which may be involved in the mechanisms of hyperalgesia.

[Pegylated interferon alpha 2a in treating chronic hepatitis B patients].

OBJECTIVE: To evaluate the efficacy and safety of pegylated interferon alpha 2a (PEG-IFN alpha-2a) in treating patients with chronic hepatitis B. METHOD: Seventy-two patients with chronic hepatitis B were assigned to a PEG-IFN alpha-2a (experimental) group (n=42) and an interferon alpha (control) group (n=30) randomly. Each patient in the experimental group received 180 microg PEG-IFN alpha-2a every week. Each patient in the control group received 500 MU interferon alpha every day. All the patients were treated for 48 weeks, and then were followed for another 48 weeks with no treatment. RESULTS: At the end of the 12th week, the rate of HBeAg negative cases was 30% in the PEG-IFN alpha-2a group, which was much higher than in the control group (x2 = 4.162, P < 0.05). The values of HBeAg and the log value of HBV DNA in the PEG-IFN alpha-2a group were much lower than the values before the treatment (t = 2.689, t = 4.080, P <0.01), but there was no difference between before and after treatment in the control group ( t = 1.229, t = 1.009, P > 0.05). At the end of the 24th week, the rate of HBeAg negative cases in the PEG-IFN alpha-2a group was much higher than that in the control group (x2=6.190, P < 0.05). The value of HBeAg and the log value of HBV DNA in the PEG-IFN alpha-2a group were much lower than in the control group (t=2.215, t=2.122, P < 0.05). At the end of the 48th week, besides the reduction mentioned above, the rate of cases with HBeAg/antiHBe seroconversion and normalization of ALT and complete responsiveness in the PEG-IFN alpha-2a group were all much higher than those in the control group (x2=5.771, x2=5.617, x2=5.308, P < 0.05). At the end of 48 weeks with no treatment, all the parameters mentioned above in the PEG-IFN alpha-2a group were much better than those in the control group and they remained so, but they were different in the control group (x2=11.943, t=3.439, t=6.111, x2=9.930, x2=9.522, x2=7.920, P < 0.01). Nine patients in the PEG-IFN alpha-2a group had liver biopsies before their treatment and also at the end of their treatment. The expressions of HBsAg and HBcAg were decreased at the end of the treatment. The rate of expression of HBsAg in the liver tissues before the treatment was 88.9% but only 22.2% at the end of the treatment (x2=8.001, P < 0.01). The rate of expression of HBcAg in the livers before treatment was 66.7% but only 33.3% at the end of the treatment. Before and at the end of the PEG-IFN alpha-2a treatment, there were no significant changes in the degrees of inflammation and fibrosis and the quantity of collagen in the liver tissues. Three patients in the PEG-IFN alpha-2a group (10%) were HbsAg negative. Two of them were found so at the end of 32 weeks with treatment and one patient was found at the end of 24 weeks with no treatment, but there were no HBsAg negative patients in the control group. The adverse reactions that occurred in the PEG-IFN alpha-2a and in the control groups were similar. CONCLUSION: PEG-IFN alpha-2a was effective in inhibiting HBV replication. The effect of PEG-IFN alpha-2a was lasting. PEG-IFN alpha-2a was well tolerated during our treatment.

Activation and sensitization of C and Adelta afferent fibers mediated by P2X receptors in rat dorsal skin.

The present study investigated the activation and sensitization effects of local injection of P2X receptor agonist alpha,beta-methylene ATP (alphabeta-meATP) into the receptive fields of afferent fibers innervating dorsal hairy skin in anesthetized rats. Single unit activities of afferent fibers were recorded by means of isolation of the fiber filaments from the dorsal cutaneous nerve branch. A total of 237 fibers were obtained. Of these, 67 were classed as C fibers, 104 as Adelta fibers and 66 as Abeta fibers. When alphabeta-meATP (0.1-100 microM, 10 microl) was injected subcutaneously into the receptive fields of these units, C and Adelta fibers demonstrated a dose-related increase in the discharge rates of the response. The activated proportion of C and Adelta fibers with a response to the drug also increased with dose. However, Abeta fibers did not exhibit significant activation. Furthermore, injection of alphabeta-meATP (10 microl) at a concentration of 100 microM resulted in a significant decrease of mechanical thresholds in C and Adelta fibers compared with pre-injection baseline (P < 0.05). In control experiments, injection of the vehicle phosphate-buffered saline (PBS, 10 microl) had no effect on all units tested. alphabeta-meATP (100 microM, 10 microl) followed by pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), a P2X receptor antagonist, successfully blocked the activation and sensitization effects of alphabeta-meATP on C and Adelta fibers tested. These results suggest that peripheral P2X receptors are involved in mediating peripheral excitation of C and Adelta fibers.

[Local injection of alpha, beta-methylene ATP induces excitation of primary afferent fibers in rats].

OBJECTIVE: To observe the excitation and sensitization of dorsal cutaneous primary afferent fibers induced by P2X agonist alpha, beta-methylene ATP (alphabetame-ATP) in rats. METHODS: By means of single fiber electrophysiological recordings on the nerve filaments isolated from the dorsal cutaneous branches of the T(9)-T(13) spinal nerves, the effects of alphabetame-ATP (100 micromol/L, 10 microl) injection into the cutaneous receptive field on the mechanical threshold and spontaneous discharge of rat primary sensory afferent units were observed. RESULTS: The mean mechanical threshold of Adelta and C fibers prior to alphabetame-ATP injection were 0.384+/-0.018 and 0.943+/-0.102 mN, and lowered to 0.304+/-0.013 and 0.659+/-0.071 mN after the injection, respectively (P<0.05, P<0.01). The mechanical threshold of the Abeta fibers before alphabetame-ATP injection was 0.301+/-0.019 mN, and slightly lowered to 0.288+/-0.018 mN after the injection (P>0.05). Injection of alphabetame-ATP (10 microl) into the receptive fields evoked spontaneous discharge in 7.7% of the Abeta fibers, 66.7% of Adelta fibers and 75.0% of C fibres, respectively, and the proportions of Adelta and C fibers with spontaneous discharge evoked by alphabetame-ATP were significantly greater than that of Abeta fibers (P<0.05). In the control experiments, injection of saline did not significantly affect spontaneous discharge or excite the nerve fibers. The mean discharge frequency of Adelta and C fibers increased from 0.73+/-0.24 and 0.54+/-0.21 impulses/min before injection to 3.05+/-0.65 and 8.53+/-2.04 impulses/min during the injection, with subsequent reduction to 2.40+/-0.60 and 6.68+/-1.68 impulses/min in the following 5 min (P<0.05). In contrast to Adelta and C fibers, Abeta fibers exhibited no significant changes in the mean discharge frequency in response to alphabetame-ATP (0.23+/-0.09 impulses/min before injection, 0.28+/-0.09 impulses/min during injection and 0.22+/-0.14 impulses/min after injection, P>0.05). The excitatory effects of alphabetame-ATP on the discharge rate in Adelta and C primary afferent terminal could be observed in the entire course of experiment. CONCLUSION: Peripheral application of alphabetame-ATP, an ATP analogue, excites and sensitizes a subpopulation of Adelta and C fibers but not Abeta fibers of rat dorsal cutaneous primary afferent fibers.

Local application of morphine suppresses glutamate-evoked activities of C and Adelta afferent fibers in rat hairy skin.

Behavior studies have demonstrated that local application of morphine in peripheral tissues resulted in a significant antinociceptive effect, but there has been no electrophysiological evidence to support the peripheral mechanism of opioid antinociception. The purpose of the present study was to investigate whether local application of morphine suppressed the glutamate-evoked activities of C and Adelta primary afferent fibers in dorsal hairy skin of rat in vivo. The single unit activities of the C and Adelta afferent fibers were recorded by means of isolation of the fiber filaments from the dorsal cutaneous nerve branches, and the effects of glutamate and glutamate plus morphine injected into the receptive field on these activities were determined. The results revealed that most of the C and Adelta fibers were excited significantly by local injection of glutamate (0.3 mM), with the percentage being 81% (22/27, for C fibers) and 73% (36/49, for Adelta fibers), respectively. The glutamate-induced excitatory response was significantly suppressed by co-injection of morphine (1.0 mM). The mean discharge rates of C fibers and Adelta fibers decreased from 28.96 +/- 6.85, 28.99 +/- 3.79 impulses/min to 4.40 +/- 1.76, 2.72 +/- 0.71 impulses/min, respectively. The suppressing effect of morphine was reversed by pretreatment with opioid receptor antagonist naloxone (1.0 mM). These findings suggest that local application of morphine can suppress the glutamate-evoked activities of the fine fibers in rat hairy skin and thus provide an electrophysiological evidence for peripheral antinociception of opioids.