Current role and future perspectives of electroacupuncture in circadian rhythm regulation.

In recent years, in-depth research on chronobiology has been conducted, and the circadian rhythm has become a new target for the treatment of diseases. Circadian rhythms are closely related to the normal physiological functions of organisms. Increasing evidence indicates that circadian rhythm disorders are the pathological basis of diseases such as sleep disorders, depression, cardiovascular diseases, and cancer. As an economical, safe, and effective treatment method, electroacupuncture has been widely used in clinical practice. In this paper, we summarize the current literature on electroacupuncture's regulation of circadian rhythm disorders and circadian clock genes. In addition, we briefly explore the optimization of electroacupuncture intervention programmes and the feasibility of implementing electroacupuncture intervention programmes at selected times in clinical practice. We conclude that electroacupuncture may have good application prospects in circadian rhythm regulation, but this conclusion needs to be confirmed by clinical trials.

Comparative Efficacy of Neuromodulation Technologies for Overactive Bladder in Adults: A Network Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: The aim of this study was to investigate the comparative efficacy of neuromodulation technologies for overactive bladder (OAB) syndrome in adults. DATA SOURCES: A computerized search was conducted of Cochrane Library, EMBASE, MEDLINE (via PubMed), Web of Science, CNKI, Wan Fang Data, and ClinicalTrials.gov up to April 21, 2022. STUDY SELECTION: The search selected clinical trials with random allocation to percutaneous tibial nerve stimulation (PTNS), transcutaneous tibial nerve stimulation (TTNS), vaginal electrical stimulation (VES), sacral neuromodulation (SNM), parasacral stimulation (PS), pudendal neuromodulation, or placebo. DATA EXTRACTION: The main outcomes were the voiding diary, OAB-related quality of life, and positive response rate. The Cochrane Risk of Bias tool (RoB 2.0) was used to assess the risk of bias of each included study, and the Grading of Recommendations Assessment, Development, and Evaluation tool was used to evaluate the overall evidence quality of key outcomes. DATA SYNTHESIS: The study included 21 randomized controlled trials involving 1433 participants, and all trials were used for the meta-analysis. In the network meta-analyses, five of six neuromodulation technologies, including PTNS, TTNS, VES, SNM, and PS, were related to higher efficacy than the placebo. Ranking probability showed that SNM was the most efficacious therapy for improving OAB-related quality of life, urinary episodes, and urinary frequency. For urgency incontinence episodes and the number of pads, PTNS and TTNS were the most efficacious modalities, respectively. CONCLUSION: Neuromodulation technologies, including PTNS, TTNS, VES, SNM, and PS, may be effective and safe solutions for OAB syndrome in adults. Moreover, SNM is the most efficacious regimen for OAB-related quality of life, urinary episodes, and urinary frequency. PTNS and TTNS are the most efficacious modalities for reducing urgency incontinence episodes and the number of pads, respectively. Future studies should pay more attention to the quality of study design and report, patients who may benefit the most from neuromodulation, and the long-term effect, cost-effectiveness, and satisfaction of neuromodulation.

The NLR family pyrin domain containing 3 inflammasome in the mechanism of electroacupuncture: Current status and future perspectives.

Electroacupuncture, which is the most widely used alternative medicine treatment, has been gradually recognized for its effectiveness; however, its mechanism of action is not fully understood. The NLR family pyrin domain containing 3 (NLRP3) inflammasome is a thoroughly studied inflammasome that is closely associated with Alzheimer's disease, spinal cord injury, and other diseases and plays an important role in the diagnosis and treatment of human immune system diseases. In recent years, some scholars have found that the NLRP3 inflammasome is a part of the mechanism of action of electroacupuncture, which has attracted further attention. In the current review, using "electroacupuncture" and "NLRP3 inflammasome" as keywords and based on the existing randomized controlled trials or clinical trials, we summarize the mechanisms of electroacupuncture targeting NLRP3 inflammasome in the treatment of different diseases and discuss how to optimize the electroacupuncture protocol to obtain thorough mechanisms of NLRP3 inflammasome in electroacupuncture and improve the level of evidence.

Do patients with and survivors of COVID-19 benefit from telerehabilitation? A meta-analysis of randomized controlled trials.

Background: Coronavirus disease 2019 (COVID-19) significantly impacts physical, psychological, and social functioning and reduces quality of life, which may persist for at least 6 months. Given the fact that COVID-19 is a highly infectious disease and therefore healthcare facilities may be sources of contagion, new methods avoiding face-to-face contact between healthcare workers and patients are urgently needed. Telerehabilitation is the provision of rehabilitation services to patients at a distance via information and communication technologies. However, high-quality evidence of the efficacy of telerehabilitation for COVID-19 is still lacking. This meta-analysis aimed to investigate the efficacy of telerehabilitation for patients with and survivors of COVID-19. Methods: We searched the Cochrane Library, EMBASE, Medline (via PubMed), PEDro, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform from January 1st, 2020 to April 30th, 2022 for randomized controlled trials published in English, which aimed to evaluate the efficacy of telerehabilitation vs. face-to-face rehabilitation, usual care, or no treatment for COVID-19. Methodological quality and overall evidence quality of the included studies were assessed. The statistical reliability of the data was quantified using the trial sequential analysis. Results: Seven randomized controlled trials with eight comparisons were included and all of them were used for meta-analysis. The meta-analyses of absolute values showed the superiority of telerehabilitation over no treatment or usual care for dyspnea (Borg scale: mean difference = -1.88, -2.37 to -1.39; Multidimensional dyspnea-12: mean difference = -3.70, -5.93 to -1.48), limb muscle strength (mean difference = 3.29; 2.12 to 4.47), ambulation capacity (standardized mean difference = 0.88; 0.62 to 1.14), and depression (mean difference = -5.68; -8.62 to -2.74). Significant improvement in these variables persisted in the meta-analyses of change scores. No significant difference was found in anxiety and quality of life. No severe adverse events were reported in any of the included studies. Conclusions: Moderate- to very low-quality evidence demonstrates that telerehabilitation may be an effective and safe solution for patients with and survivors of COVID-19 in dyspnea, lower limb muscle strength, ambulation capacity, and depression. Further well-designed studies are required to evaluate the long-term effects, cost-effectiveness, and satisfaction in larger samples.

The Effect of Fu's Subcutaneous Needling Combined with Reperfusion Approach on Surface Electromyography Signals in Patients with Cervical Spondylosis and Neck Pain: A Clinical Trial Protocol.

Background: Neck pain is one of the most common musculoskeletal diseases. Fu's subcutaneous needling therapy is a special acupuncture method that targets muscle trigger points. It has been proven to have a positive effect on the treatment of neck pain. The access to its curative effect may be related to the improvement of muscle and soft tissue condition. The purpose of this study is to evaluate the outcome of Fu's subcutaneous needling therapy for patients with neck pain by collecting changes in the sEMG of the patient's neck muscles and related data from evaluation scales and explore the feasibility and safety of Fu's subcutaneous needling therapy for neck pain. Methods: 72 patients meeting the inclusion criteria were randomly divided into FSN group and acupuncture group for corresponding treatment. FSN group was treated once every other day for 5 consecutive treatments; the acupuncture group was treated once a day for 10 consecutive treatments. Result: Outcome indicators were measured at baseline, after the first treatment and the end of the treatment. Primary outcome indicators: average EMG (AEMG) and (mean power frequency) MPF of sternocleidomastoid muscle and superior trapezius muscle. Secondary outcome indicators: Mc Gill pain questionnaire (MPQ), neck disability index (NDI), and adverse reactions. Conclusions: This study will explore the efficacy, safety, and possible mechanism of Fu's subcutaneous needling therapy for patients with neck pain, thus to provide more evidence support for clinical decision-making. This trial is registered with Chinese Clinical Trial Register Center (registration number ChiCTR2100043529).

Comparison of Interferon-α-based therapy and nucleos(t)ide analogs in preventing adverse outcomes in patients with chronic hepatitis B.

BACKGROUND: Whether interferon (IFN)-α therapy is better than nucleos(t)ide analogs (NAs) in the prevention of adverse outcomes, including hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is still uncertain or controversial. This study aimed to compare the cumulative incidence of adverse outcomes in patients with CHB on IFN-α- and NA-based therapies. METHODS: This was a retrospective study of patients with CHB on antivirals. Patients treated with IFN-α (IFN-α or peginterferon-α) with or without NAs were defined as the IFN-α group, and those only receiving NAs were defined as the NAs group. Propensity score matching (PSM) was used to minimize baseline bias. Cox regression models were performed to select possible factors related to adverse outcomes development. RESULTS: All 1247 patients were divided into the IFN-α (n = 877) and NAs (n = 370) groups. 26patients (20 and 6 in the NAs and IFN-α groups) developed adverse outcomes (decompensated cirrhosis, liver failure, HCC, liver transplantation and deaths) during a median follow-up of 5.2 years. The cumulative adverse outcomes occurrence at 10 years was significantly lower in the IFN-α group than in the NAs group in all (1.1% vs. 11.9%, P <0.001) and treatment-naïve (1.1% vs. 12.4%, P <0.001) patients. Similar trends were observed after PSM and differentiation of cirrhosis. Multivariate analysis before and after PSM showed that IFN-α-based treatment was independently associated with a lower adverse outcomes incidence (before/after PSM: P = 0.001/P = 0.002). HCC risk stratification analyses revealed that the superiority of IFN-α in preventing HCC was more significant in patients with high-risk HCC. CONCLUSIONS: IFN-α-based therapy was superior to NAs in preventing adverse outcomes in patients with CHB regardless of cirrhosis, and in reducing HCC in those with a high risk of HCC.

Effect of vagus nerve stimulation paired with rehabilitation for upper limb function improvement after stroke: a systematic review and meta-analysis of randomized controlled trials.

Vagus nerve stimulation (VNS) could potentially facilitate arm function recovery after stroke. The aim of this review was to evaluate the effect of VNS paired with rehabilitation on upper limb function recovery after stroke. We considered randomized controlled trials (RCTs) that used VNS paired with rehabilitation for the improvement of upper limb function after stroke and were published in English. Eligible RCTs were identified by searching electronic databases, including MEDLINE, Web of Science, Embase, CENTRAL and PEDro, from their inception until June 2021. Quality of included studies was assessed using PEDro score and Cochrane's risk of bias assessment. A meta-analysis was performed on the collected data. Five studies with a total of 178 participants met the inclusion criteria. Overall, the present meta-analysis revealed a significant effect of VNS on Fugl-Meyer Assessment for Upper Extremity (FMA-UE, MD = 3.59; 95% CI, 2.55-4.63; P < 0.01) when compared with the control group. However, no significant difference was observed in adverse events associated with device implantation between the invasive VNS and control groups (RR = 1.10; 95% CI, 0.92-1.32; P = 0.29). No adverse events associated with device use were reported in invasive VNS, and one was reported in transcutaneous VNS. This study revealed that VNS paired with rehabilitation can facilitate the recovery of upper limb function in patients with stroke on the basis of FMA-UE scores, but the long-term effects remain to be demonstrated.

Increased serum CXCL10 levels are associated with clinical severity and radiographic progression in patients with lumbar disc degeneration.

BACKGROUND: Lumbar intervertebral degenerative disc disease (IDD) is a multifaceted progressive condition that commonly occurs in conjunction with lumbar disc herniation (LDH). CXCL10 mRNA appears to be increased in both IDD and LHD. OBJECTIVE: This study was performed to identify the relationship between serum CXCL10 levels and disease severity in patients with IDD. METHODS: 136 IDD patients with low back pain, 127 asymptomatic volunteers and 120 healthy controls were enrolled. Serum CXCL10 protein concentrations were detected using commercial human CXCL10 ELISA Kits. Serum CXCL10 mRNA were examined using qRT-PCR. Clinical severity was assessed using the visual analog scale (VAS) and Oswestry Disability Index(ODI) scores. Radiographic severity was defined using the MRI-based Pfirrmann classification of disc degeneration. Receiver operating characteristic (ROC) curve analysis was used in estimating the correlation between CXCL10 and Pfirrmann grade. The cross-sectional area (CSA) of the lumbar multifidus muscle (LMM) and psoas major (PM) were calculated, and fat infiltration was evaluated by Ropponen-Kjaer criteria. RESULTS: Serum CXCL10 concentrations were markedly raised in IDD patients with low back pain in contrast to asymptomatic individuals and healthy controls. Serum CXCL10 levels were positively associated with Pfirrmann grade. ROC curve analysis indicated that serum CXCL10 correlated well with Pfirrmann grade. In addition, serum CXCL10 concentrations were significantly higher in IDD patients with LMM and PM degeneration compared with IDD patients without degeneration. Increased CXCL10 levels positively correlated with VAS and ODI scores, as well as decreased CSA and fat filtration of the LMM and PM. CONCLUSION: Increased serum CXCL10 levels correspond to clinical severity and radiographic progression in IDD patients.

The Effect and Mechanism of Exercise Training on Rats with Poststroke Depression Based on the Intestinal Flora.

Depression of poststroke depression (PSD) is the most common neuropsychiatric complication after stroke. Patients with PSD had higher mortality, more cognitive disorder, lower quality of life, and higher suicidal tendency. The pathogenesis of PSD mainly involves neurotransmitter inflammatory factors, HPA and BDNF. Enteral dysfunction and intestinal flora disorders caused by stroke can participate in the pathogenesis of PSD through various ways, such as immune, endocrine, and nervous system. In this experiment, we used exercise training as an intervention means to explore the curative effect and possible mechanism by observing the changes of behavior, inflammatory factors, and intestinal flora in rats. The results show that the mechanism of exercise training to improve the depressive behavior of rats may be related to inhibiting the expression of proinflammatory factors and increasing the number of lactic acid bacteria in the intestine.

Impact of Hepatic Steatosis on the Antiviral Effects of PEG-IFNα-2a in Patients with Chronic Hepatitis B and the Associated Mechanism.

OBJECTIVE: To investigate the risk factors for hepatic steatosis in chronic hepatitis B (CHB), to determine its correlation with liver necroinflammation and fibrosis and response to peginterferon alpha-2a (PEG-IFNα-2a) antiviral therapy, and to explore the mechanisms underlying the poor antiviral effect of PEG-IFNα-2a in CHB patients with hepatic steatosis. METHODS: We analysed the impact of hepatic steatosis on the antiviral effect of PEG-IFNα-2a on CHB patients in a cohort of 226 patients who underwent pretherapeutic liver biopsy. To assess the complete response (CR), virological response (VR), and biochemical response (BR), the 226 patients were treated with PEG-IFNα-2a for 48 weeks and were followed-up for 24 weeks. The expressions of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in the liver tissue were detected in all patients to explore the possible mechanism of hepatic steatosis with regard to antiviral effects. RESULTS: The patients were divided into four groups based on the severity of hepatic steatosis: 119 with no steatosis, 76 with mild steatosis, 22 with moderate steatosis, and 9 with severe steatosis. In the hepatic steatosis groups, the proportions of male patients, patients aged >40 years, patients with hyperuricaemia, patients with a BMI > 23 kg/m2, and total cholesterol (TC), triglyceride (TG), glucose (GLU), and uric acid (UA) levels were significantly higher than those in the group without steatosis, whereas the alanine aminotransferase (ALT) and aspartate transaminase (AST) levels were significantly lower than those in the group without steatosis. The multivariate analysis results indicated that a BMI > 23 kg/m2 was independently associated with CHB patients with hepatic steatosis; the levels of baseline AST and UA were independently associated with CHB patients with significant hepatic steatosis, and the baseline AST level was independently associated with significant liver fibrosis. After 48 weeks of treatment and 24 weeks of follow-up, the rates of CR, VR, and BR had gradually decreased, whereas the severity of hepatic steatosis had increased. CONCLUSION: Hepatic steatosis can reduce the efficacy of PEG-IFNα-2a in the treatment of CHB patients, and its mechanism may be related to the different HBcAg expression patterns in liver tissue.

Three-terminal spin/charge current router.

Topological insulator materials have wide applications in electronic and spintronic devices by utilizing the protected edge states. In this paper, based on these topological edge states and energy gaps, we propose some types of spin/charge current router in a three-terminal system consisting of silicene-like nanoribbons (SiNRs). The current is well controlled by the helical edge states of zigzag SiNRs (ZSiNRs) and external fields. Using the tight-binding model and non-equilibrium Green's function theory, we investigate three types of such router. The first type is a spin current shunter which separates the spin-up and spin-down current into different leads. The second type is a spin filter which separates the spin-polarized electrons into one of those leads. The last type is a charge current switcher which switches the charge current from one lead to the other lead. The local current distribution is calculated for the specific electron path. We find that the small Rashba does not destroy the filtering properties of the system. Besides, as an example, we employ the Landauer-Büttiker formula to obtain the current-voltage curves of the first type router and investigate the transmittance reciprocity relations in such a three-terminal system. We believe these proposed spin/charge current routers, which can separate the specific current into the expected lead, have potential applications in the future spintronics designs.

Predictive value of plasmacytoid dendritic cells and Toll-like receptor-9 regarding the treatment efficacy of interferon-α in HBeAg-positive chronic hepatitis B patients.

Hepatitis B virus (HBV) infection represents a public health threat and a challenge for the medical community. Untimely treatment may lead to liver cirrhosis and even liver cancer. At present, the major treatment for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients includes administration of interferon-α (IFN-α), which has anti-viral and immunomodulatory effects. Plasmacytoid dendritic cells (pDCs) and Toll-like receptor-9 (TLR-9) have important roles in anti-viral therapy. However, their predictive value regarding the efficacy of IFN-α treatment of HBeAg-positive chronic hepatitis B (CHB) patients has remained elusive. A total of 178 patients with CHB and HBeAg-positive status, who had not received any previous anti-HBV treatment, were enrolled in the present study. All patients were treated with IFN-α. HBV DNA load, hepatitis B surface antigen and serum alanine aminotransferase were measured prior to and following 48 weeks of treatment. According to HBV levels, the patients were divided into a response group and non-responders group. To determine the amount of pDCs, blood dendritic cell antigen 2 (BDCA-2)- and immunoglobulin-like transcript 7 (ILT7)-expressing cells in liver biopsies were detected using immunohistochemistry. TLR-9 expression in peripheral blood mononuclear cells was determined by reverse transcription-quantitative PCR. There was no significant difference in the proportion of pDCs (BDCA-2; ILT7) and TLR-9 mRNA expression between the response group and the non-responders group prior to IFN-α treatment. After IFN-α treatment, BDCA-2, ILT7 and TLR-9 mRNA expression was obviously increased in the response group compared with that in the non-responders group (P<0.05). Increased expression of BDCA-2, ILT7 and TLR-9 mRNA was negatively correlated with HBV DNA (P<0.05). Increased levels of pDCs and TLR-9 were negatively correlated with HBV DNA, and were thus capable of predicting the IFN-α treatment response in patients with CHB and HBeAg-positive status.

Modeling three-dimensional invasive solid tumor growth in heterogeneous microenvironment under chemotherapy.

A systematic understanding of the evolution and growth dynamics of invasive solid tumors in response to different chemotherapy strategies is crucial for the development of individually optimized oncotherapy. Here, we develop a hybrid three-dimensional (3D) computational model that integrates pharmacokinetic model, continuum diffusion-reaction model and discrete cell automaton model to investigate 3D invasive solid tumor growth in heterogeneous microenvironment under chemotherapy. Specifically, we consider the effects of heterogeneous environment on drug diffusion, tumor growth, invasion and the drug-tumor interaction on individual cell level. We employ the hybrid model to investigate the evolution and growth dynamics of avascular invasive solid tumors under different chemotherapy strategies. Our simulations indicate that constant dosing is generally more effective in suppressing primary tumor growth than periodic dosing, due to the resulting continuous high drug concentration. In highly heterogeneous microenvironment, the malignancy of the tumor is significantly enhanced, leading to inefficiency of chemotherapies. The effects of geometrically-confined microenvironment and non-uniform drug dosing are also investigated. Our computational model, when supplemented with sufficient clinical data, could eventually lead to the development of efficient in silico tools for prognosis and treatment strategy optimization.

Optimization of dosage ratio of chlorogenic acid and gardenia glycosides in the treatment of rats with fatty liver disease induced by high-fat feed.

OBJECTIVE: To investigate the optimal dosage ratio of chlorogenic acid and gardenia glycosides in treating the rates with fatty liver disease induced by high-fat feed. METHODS: A rat model of non-alcoholic fatty liver disease (NAFLD) was established by using a high-fat diet. According to mathematical model "uniform design", varying doses of chlorogenic acid and gardenia glycosides have been combined to form 6 medications for the treatment of NAFLD. Samples were then taken to observe pathological changes of the liver tissue (HE staining); changes in the fat metabolism pathway e.g. triglyceride (TG) and free fatty acid (FFA) content; alterations in liver function, i.e. serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity; and differences in Malondialdehyde (MDA) and superoxide dismutase (SOD) content in the liver tissue. Multiple regression analysis was conducted to test the optimal dosage ratio of chlorogenic acid and gardenia glycosides. RESULTS: Fatty degeneration and vacuole-like changes of different degrees occurred in hepatic cells of the model group. Markers for fat metabolism, serum ALT and AST activities, and expression of MDA in liver tissue significantly increased, while SOD decreased. Combination of 90 mg chlorogenic acid and 90 mg Gardenia glycosides was the optimal dosage ratio of chlorogenic acid and gardenia glycosides in the treatment of rats with fatty liver induced by high-fat diet. CONCLUSION: Chlorogenic acid of 90 mg plus gardenia glycosides of 90 mg was the best combination in the treatment of fatty liver disease in rats induced by high-fat feed.

Inhibitory Effect of Gardenoside on Free Fatty Acid-Induced Steatosis in HepG2 Hepatocytes.

Gardenoside is one of the most important effective extractions of a herb for its hepatoprotective properties. The aim of this study was to address the mechanism of Gardenoside on HepG2 cellular steatosis induced by free fatty acids (FFAs). The model of HepG2 steatosis was duplicated by oleic and palmitic acid at the proportion of 2:1 (FFAs mixture) for 24 h, then lipid toxicity was induced. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) were used to detect cell viability and Oil Red O staining method was used to judge the lipid accumulation respectively. Inflammatory cytokines TNF-α, IL-1ß, IL-6 and intracellular NFκB were measured after 24 h. The steatosis was significantly decreased after Gardenoside treatment without cytotoxicity. TNF-α, IL-1ß, IL-6 were modulated to HepG2 cells by treatment of Gardenoside. In the meantime, the activation of NFκB was inhibited by Gardenoside. Gardenoside has a protective effect on FFA-induced cellular steatosis in HepG2 cells which indicates that Gardenoside might be a potential therapeutic herb against NASH by suppressed supernatant inflammatory cytokine production and intracellular NFkB activity.

A Mechanistic Assessment of the Discordance between Normal Serum Alanine Aminotransferase Levels and Altered Liver Histology in Chronic Hepatitis B.

To understand the mechanisms underlying the discordance between normal serum alanine aminotransferase (ALT) levels and significant alterations in liver histology of chronic hepatitis B virus (HBV) infection with persistent normal ALT (PNALT) or minimally elevated ALT. A total of 300 treatment-naive chronic HBV-infected patients with PNALT (ALT ≤ upper limit of normal [ULN, 40 U/ml]) or minimally elevated ALT (1-2×ULN) were retrospectively enrolled. All patients underwent liver biopsy and histological changes were analyzed along with biochemical and HBV markers. Among 300 participants, 177 were HBeAg-positive and 123 HBeAg-negative. Significant histologic abnormalities were found in 42.9% (76/177) and 52.8% (65/123) of HBeAg-positive and HBeAg-negative patients, respectively. Significant fibrosis, which is a marker of prior injury, was more frequently detected than significant necroinflammation (suggesting active liver injury) in both HBeAg-positive and -negative groups, suggesting that liver injury occurred intermittently in our cohort. No significant differences were noticed in the percentage of patients with severe fibrosis between HBeAg-positive and negative phases or between ages 30 and 40 and over 40, suggesting that the fibrosis was possibly carried over from an early phase. Finally, lowering ALT ULN (30 U/L for men, 19 U/L for women) alone was not adequate to increase the sensitivity of ALT detection of liver injury. However, the study was limited to a small sample size of 13 HBeAg-positive patients with ALT in the revised normal range. We detected significant liver pathology in almost 50% of chronic HBV infected patients with PNALT (ALT ≤ 40 U/ml) or minimally elevated ALT. We postulated that small-scale intermittent liver injury was possibly responsible for the discordance between normal serum ALT and significant liver changes in our cohort.

[Sustained efficacy of alpha-interferon therapy combined with Yixuesheng Capsule in treatment of chronic hepatitis B].

OBJECTIVE: To observe the difference between the combination therapy of alpha-interferon (IFN-alpha) therapy Yixuesheng Capsule and the monotherapy of IFN-alpha in treatment of chronic hepatitis B. METHOD: A total of 288 patients with HBeAg-positive chronic hepatitis B proven by liver biopsy were included in this study. During the individualized therapy, they received hypodermic injection of IFN-alpha 1b, with 5 MU x time(-1) and three times x w(-1). Of them, 125 patients received combination therapy with Yixuesheng Capsule for three months, with 1.0 g/time and three times/d; and 163 patients received only IFN-alpha 1b (the IFN-alpha monotherapy group). After the course of therapy, all patients were followed up for at least 24 months. The intention-to-treat analysis was adopted for statistic analysis. RESULT: The two groups showed no statistical significance by gender, age, liver necroinflammation grading, liver fibrosis staging, serum ALT levels, serum HBV DNA levels and IFN-alpha therapy course. The whole course and the 24-month follow-up visit cover all of 112 patients in the combination treatment group and 141 cases in the IFN-alpha monotherapy group. The response rates of the combination treatment group and the IFN-alpha monotherapy group were 48.0% (60/125) and 35.0% (57/163) (x = 4.980, P = 0.026) at the end of treatment, respectively, 45.6% (57/125) and 33.1% (54/163) (x2 = 4.645, P =0.031) at the end of 12-month-follow-up period, respectively, and 38.4% (48/125) and 32.5% (53/163) (x2 = 1.076, P = 0.300) at the end of 24-month follow-up period, respectively. CONCLUSION: The combination treatment with IFN-alpha and Yixuesheng Capsule shows a slightly better sustained efficacy on HBeAg-positive chronic hepatitis B patients compared with IFN-alpha monotherapy.