Drug recommendation for optimization on treatment outcome for MDR/RR-TB based on a multi-center, large scale, retrospective cohort study in China.

OBJECTIVE: With the change in drug-resistant pattern, MDR/RR-TB was faced with underlying changes in regimens. A multi-center, large-scale, retrospective study performed aims to provide a recommendation of drug selection on optimization of outcome for the patients. METHOD: The study was conducted in six TB-specialized hospitals in China. Patients were included from 2018-2021 and followed up throughout the treatment. Using a multivarariable and propensity score-matched logistic regression analysis, we evaluated associations between outcomes and drug use, as well as clinical characteritics. RESULTS: Of 3112 patients, 74.29% had treatment sucess, 14.52% lost to follow-up, 9.67% failure, and 1.51% died. Treatment success was positively associated with Bedaquiline(Bdq), Linezolid(Lzd), and Cycloserin(Cs). Capreomycin(Cm) increased the risk of unfavorable outcomes. other drugs such as Amikacin(Amk) and clofazimine had no significant effect on outcomes. If isolates were susceptible to fluoroquinolones(FQs), FQs could decrease the risk of unfavorable outcomes. CONCLUSIONS: The recommendation order for the treatment of MDR/RR-TB is Bdq, Lzd, and Cs. FQs were decreased in use intensity. Injection drugs, whether Amk or Cm, are not recommended.

Efficacy and safety of the all-oral bedaquiline-containing regimen as treatment for pediatric multidrug/rifampicin-resistant tuberculosis: a multicenter, retrospective, cohort study.

OBJECTIVE: The study aimed to observe the efficacy and safety of an all-oral bedaquiline (BDQ)-containing regimen for pediatric multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) through a multicenter, retrospective study in China. METHODS: In the study, pediatric patients receiving all-oral BDQ-containing regimen (BDQ group) with clinical matched control group were included, the control group received an injection-containing regimen. The treatment outcomes and the incidence of adverse events (AEs) were compared and analyzed. RESULTS: 79 pediatric patients were enrolled, including 37 cases in BDQ group and 42 cases in the control group, the median age was 12 {8-16} and 11 {9-15} in both groups respectively. Favorable treatment outcome and cure rate in BDQ group were significantly higher than those in control group (100%vs 83.3%, p 0.03; 94.6%vs 63.3%, p 0.00). Median time of sputum culture conversion in BDQ group was significantly shorter than that in the control group (4 weeks vs 8 weeks, p 0.00). The incidence of AEs in the BDQ group was significantly less than that in the control group (48.6% vs 71.4%, p 0.03). No AEs leading to treatment discontinuation of BDQ occurred. CONCLUSIONS: The all-oral BDQ-containing regimens may be effective and safe in the Chinese pediatric population.

The Correlations of Minimal Inhibitory Concentration Values of Anti-TB Drugs with Treatment Outcomes and Clinical Profiles in Patients with Multidrug-Resistant Tuberculosis (MDR-TB) in China.

Objective: It is a challenge to obtain satisfactory treatment outcomes for patients with multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB); the study aims to correlate the Minimum Inhibitory Concentration (MIC) value of drugs with the outcome of patients with MDR/RR-TB to obtain an understanding for better regimens and optimal outcomes. Methods: The patients diagnosed with MDR/RR-TB were retrospectively enrolled from January 1, 2018 to December 31, 2019, recorded clinical characteristics, MIC DST (Drug Susceptibility Test) results, and followed the treatment outcome. The data were analyzed on the correlations of MIC DST values with outcomes and clinical characteristics. Results: A total of 276 patients with MDR/RR-TB were included, containing 98 cases (35.5%) with newly treated patients and 178 cases (64.5%) with re-treated patients. A total of 220 cases recorded treatment success (79.7%) and 49 cases recorded treatment failure or died. MIC values of isoniazid (H), moxifloxacin (Mfx), and ethionamide (Eto) in newly treated patients were lower than those in retreated patients, and resistance levels of Mfx and H were closely associated with the treatment outcome (P < 0.05) while those of other drugs had no close association with treatment outcome. Conclusions: MIC values of some anti-TB drugs, such as fluoroquinolones (FQs) and H, can reflect the treatment outcome for patients with MDR/RR-TB, which can contribute to making regimens for better treatment outcomes.

Effectiveness and safety of bedaquiline-containing regimens for treatment on patients with refractory RR/MDR/XDR-tuberculosis: a retrospective cohort study in East China.

OBJECTIVE: Refractory rifampicin-resistant/multidrug resistant/extensively-drug resistant tuberculosis (RR/MDR/XDR-TB) were defined as patients infected with Mycobacterium tuberculosis (MTB) resistant to rifampicin(RR-TB), or at least resistant to rifampicin and isoniazid (MDR-TB) or added resistant to fluoroquinolones (FQs) and one of second line injectable agents (XDR-TB), a patient for whom an effective regimen (fewer than 4 effective agents due to adverse events (AEs) or multiple drug resistances) cannot be developed. To compare the effectiveness and safety of bedaquiline (BDQ)-containing and BDQ-free regimens for treatment of patients with refractory RR/MDR/XDR-TB. METHODS: Patients with refractory RR/MDR/XDR-TB receiving BDQ-containing regimens (BDQ group, n = 102) and BDQ-free regimens (non-BDQ group, n = 100) satisfied with included criteria were strictly included in this retrospective historical control study across East China. Culture conversion, treatment outcome, cavity closing rate, and AEs were compared between two groups. RESULTS: The baseline characteristics involved all possible aspects of patients were well balanced between two groups (p > 0.05). Culture conversion rates in the BDQ group at month 3 (89.2% vs. 66.0%), month 6 (90.2% vs 72.0%), month 9 (91.2% vs. 66.0%), and month 12 (94.1% vs 65.0%) were all significantly higher than those in non-BDQ group (p < 0.001). Similar results were observed in the cavity closing rate at month 9 (19.6% vs 8.0%, p = 0.0) and month 12 (39.2% vs 15.0%, p < 0.001). Patients receiving BDQ-containing regimens had more treatment success than those receiving BDQ-free regimens (p < 0.001; cure rate, 69.6% vs. 45.0%; complete the treatment, 22.5% vs. 18.0%; treatment success, 92.2% vs. 63.0%); the use of BDQ and combined with Linezolid or Clofazimine or Cycloserine were identified as independent predictors of treatment success and no culture reversion (P < 0.05). AEs were similarly reported in 26.5% of patients in the BDQ group and 19.0% in the non-BDQ group (p = 0.2). CONCLUSIONS: BDQ-containing regimens resulted in better treatment outcomes and similar safety relative to BDQ-free regimens for patients with refractory pulmonary RR/MDR/XDR-TB.

Risk factors and predictive model of adrenocortical insufficiency in patients with traumatic brain injury.

BACKGROUND: Neuroendocrine dysfunction after traumatic brain injury (TBI) has received increased attention due to its impact on the recovery of neural function. The purpose of this study is to investigate the incidence and risk factors of adrenocortical insufficiency (AI) after TBI to reveal independent predictors and build a prediction model of AI after TBI. METHODS: Enrolled patients were grouped into the AI and non-AI groups. Fourteen preset impact factors were recorded. Patients were regrouped according to each impact factor as a categorical variable. Univariate and multiple logistic regression analyses were performed to screen the related independent risk factors of AI after TBI and develop the predictive model. RESULTS: A total of 108 patients were recruited, of whom 34 (31.5%) patients had AI. Nine factors (age, Glasgow Coma Scale [GCS] score on admission, mean arterial pressure [MAP], urinary volume, serum sodium level, cerebral hernia, frontal lobe contusion, diffuse axonal injury [DAI], and skull base fracture) were probably related to AI after TBI. Three factors (urinary volume [X 4], serum sodium level [X 5], and DAI [X 8]) were independent variables, based on which a prediction model was developed (logit P= -3.552+2.583X 4+2.235X 5+2.269X 8). CONCLUSIONS: The incidence of AI after TBI is high. Factors such as age, GCS score, MAP, urinary volume, serum sodium level, cerebral hernia, frontal lobe contusion, DAI, and skull base fracture are probably related to AI after TBI. Urinary volume, serum sodium level, and DAI are the independent predictors of AI after TBI.

miR-574-3p inhibits proliferation and invasion in esophageal cancer by targeting FAM3C and MAPK1.

Esophageal cancer is considered as one of the leading malignancies. MicroRNA-574-3p (miR-574-3p) was used as a postoperative prognostic indicator in patients with esophageal squamous cell carcinoma. However, the underlying mechanism miR-574-3p involvement in esophageal cancer remains unclear. In this study, the expression of miR-574-3p was reduced in esophageal cancer tissues and cells. In vitro, miR-574-3p mimics and inhibitor were transfected into esophageal cancer cells (TE-1 and TE-8 cells) to up- or downregulating of miR-574-3p. miR-574-3p inhibited proliferation, migration and invasion, and promoted apoptosis in esophageal cancer cells. In addition, miR-574-3p was confirmed to target family with sequence similarity 3 member C (FAM3C) and mitogen-activated protein kinase 1 (MAPK1). miR-574-3p suppressed phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling via regulating FAM3C and MAPK1. In vivo, overexpression of miR-574-3p suppressed tumor growth in mice. Our findings indicated that miR-574-3p repressed proliferation and invasion of esophageal cancer via regulation of FAM3C and MAPK1, which provides a new biomarker for esophageal cancer treatment.

A pair of new diastereoisomeric phenylpropanoid-substituted flavan from the leaves of Ilex centrochinensis.

A pair of new diastereoisomeric flavan, containing an additional phenylpropanoid (C6-C3) unit in the molecule, has been isolated from the leaves of Ilex centrochinensis. Their structures were identified by extensive spectral analysis and comparison with the data of known analogues.

Corilagin Interferes With Toll-Like Receptor 3-Mediated Immune Response in Herpes Simplex Encephalitis.

Herpes simplex encephalitis (HSE) is the most common infectious disease of the central nervous system worldwide. However, the pathogenesis of HSE is not clear. Research has shown that the immune response mediated by the toll-like receptor 3 (TLR3) signaling pathway is essential to protect the central nervous system against herpes simplex virus (HSV) infection. However, an excessive immune response may cause tissue damage accompanied by pathological changes. The aim of this study was to explore the molecular mechanism via which corilagin controls HSE through the TLR3 signaling pathway in vitro and in vivo. Cells and mice were pre-treated with polyriboinosinic polyribocytidylic acid [poly(I:C)] or HSV type 1, and then treated with corilagin. After treatment, the mRNA and protein levels of TLR3, TLR-like receptor-associated interferon factor (TRIF), tumor necrosis factor (TNF) receptor type 1-associated DEATH domain protein (TRADD), TNF receptor-associated factor (TRAF) 3 and 6, nuclear factor-kappa-B (NF-κB) essential modulator (NEMO), P38, and interferon regulatory factor 3 (IRF3) were decreased. Interleukin-6 (IL-6), TNF-α, and type 1 interferon-ß were also decreased. When TLR3 expression was silenced or increased, corilagin still inhibited the expression of TLR3 and its downstream mediators. Hematoxylin-eosin (HE) staining and immunohistochemical examinations of mouse brain tissues revealed that corilagin lessened the degree of brain inflammation. Altogether, these results suggest that corilagin may regulate the immune response in HSE and relieve inflammatory injury by interfering with the TLR3 signaling pathway.

BODIPY-Decorated Nanoscale Covalent Organic Frameworks for Photodynamic Therapy.

Covalent organic frameworks (COFs), an emerging class of organic porous materials, have attracted intense attention due to their versatile applications. However, the deliberate fabrication of COF-based nanomaterials for nanomedical application remains challenging due to difficulty in their size- and structure-controlled synthesis and poor aqueous dispersibility. Herein, we report two boron-dipyrromethene (BODIPY)-decorated nanoscale COFs (NCOFs), which were prepared by the Schiff-base condensation of the free end -CHO (bonding defects in COFs) on the established imine-based NCOFs with the amino-substituted organic photosensitizer BODIPY via "bonding defects functionalization" approach. Thus BODIPY has been successfully nanocrystallized via the NCOF platform, and can be used for photodynamic therapy (PDT) to treat tumors. These NCOF-based PDT agents featured nanometer size (∼110 nm), low dark toxicity, and high phototoxicity as evidenced by in vitro and in vivo experiments. Moreover, the "bonding defects functionalization" approach might open up new avenues for the fabrication of additional COF-based platforms for biomedical treatment.

Emodin Attenuates Lipopolysaccharide-Induced Acute Liver Injury via Inhibiting the TLR4 Signaling Pathway in vitro and in vivo.

Aims: Emodin is an anthraquinone with potential anti-inflammatory properties. However, the possible molecular mechanisms and protective effects of emodin are not clear. The objective of this study was to investigate the possible molecular mechanisms and protective effects of emodin on lipopolysaccharide (LPS)-induced acute liver injury (ALI) via the Toll-like receptor 4 (TLR4) signaling pathway in the Raw264.7 cell line and in Balb/c mice. Methods: This study established an inflammatory cellular model and induced an ALI animal model. TLR4 was overexpressed by lentivirus and downregulated by small interfering RNA (siRNA) technology. The mRNA and protein levels of TLR4 and downstream molecules were detected in cells and liver tissue. The tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 levels in supernatant and serum were determined by ELISA. The distribution and expression of mannose receptor C type 1 (CD206) and arginase 1 (ARG1) in the liver were tested by immunofluorescence. Mouse liver function and histopathological observations were assessed. Results: Administration of emodin reduced the protein and/or mRNA levels of TLR4 and its downstream molecules following LPS challenge in Raw264.7 cells and in an animal model. Additionally, emodin suppressed the expression of TNF-α and IL-6 in cell culture supernatant and serum. The inhibitory effect of emodin was also confirmed in RAW264.7 cells, in which TLR4 was overexpressed or knocked down. Additionally, ARG1 and CD206 were elevated in the emodin groups. Emodin also decreased serum ALT and AST levels and alleviated the liver histopathological damage induced by LPS. Conclusion: Emodin showed excellent hepatoprotective effects against LPS-induced ALI, possibly by inhibiting TLR4 signaling pathways.

[Well-to-Wheels Fossil Energy Consumption and CO2 Emissions of Hydrogen Fuel Cell Vehicles in China].

Hydrogen fuel cell vehicles (FCVs) have the advantage of high energy efficiency and zero tailpipe emissions. They have been progressively commercialized in recent years. Hydrogen production has diversified technological pathways, which vary greatly in terms of energy and environmental impacts. In this study, the life cycle assessment (LCA) method was applied to evaluate well-to-wheels (WTW) fossil energy consumption and carbon dioxide (CO2) emissions of FCVs using various hydrogen production pathways. The greenhouse gases, regulated emissions, and energy use in transportation (GREET) model, developed by the Argonne National Laboratory, was applied as the assessment tool, and a China-specific database was investigated and developed to evaluate typical hydrogen production pathways. Then, we compared the WTW fossil energy consumption and CO2 emissions of FCVs with those of gasoline vehicles (GVs), hybrid electric vehicles (HEVs), and battery electric vehicles (BEVs). The results indicated that renewable-energy-based electrolysis of water and biomass gasification are two prospective hydrogen production pathways with significant WTW energy and climate benefits which can help FCVs reduce fossil energy consumption and CO2 emissions by approximately 90% more than GVs. Among the current pathways with mass adoption, hydrogen production from coke oven gas (COG) has substantial energy and CO2 mitigation benefits, which enables FCVs to achieve a lower WTW fossil energy consumption than HEVs and lower WTW CO2 emissions than HEVs and BEVs. Considering the resource reserves and technological maturity in China, hydrogen production from COG and other industrial by-products is recommended for hydrogen energy and FCV development in the short term. In the medium and long terms, utilization of renewable energy to produce hydrogen should be promoted.

Aberrant DNA Methylation Involved in Obese Women with Systemic Insulin Resistance.

BACKGROUND: Epigenetics has been recognized as a significant regulator in many diseases. White adipose tissue (WAT) epigenetic dysregulation is associated with systemic insulin resistance (IR). The aim of this study was to survey the differential methylation of genes in obese women with systemic insulin resistance by DNA methylation microarray. METHODS: The genome-wide methylation profile of systemic insulin resistant obese women was obtained from Gene Expression Omnibus database. After data preprocessing, differing methylation patterns between insulin resistant and sensitive obese women were identified by Student's t-test and methylation value differences. Network analysis was then performed to reveal co-regulated genes of differentially methylated genes. Functional analysis was also implemented to reveal the underlying biological processes related to systemic insulin resistance in obese women. RESULTS: Relative to insulin sensitive obese women, we initially screened 10,874 differentially methylated CpGs, including 7402 hyper-methylated sites and 6073 hypo-methylated CpGs. Our analysis identified 4 significantly differentially methylated genes, including SMYD3, UST, BCL11A, and BAI3. Network and functional analyses found that these differentially methylated genes were mainly involved in chondroitin and dermatan sulfate biosynthetic processes. CONCLUSION: Based on our study, we propose several epigenetic biomarkers that may be related to obesity-associated insulin resistance. Our results provide new insights into the epigenetic regulation of disease etiology and also identify novel targets for insulin resistance treatment in obese women.

Anterior transversalis fascia approach versus preperitoneal space approach for inguinal hernia repair in residents in northern China: study protocol for a prospective, multicentre, randomised, controlled trial.

INTRODUCTION: Many surgical techniques have been used to repair abdominal wall defects in the inguinal region based on the anatomic characteristics of this region and can be categorised as 'tension' repair or 'tension-free' repair. Tension-free repair is the preferred technique for inguinal hernia repair. Tension-free repair of inguinal hernia can be performed through either the anterior transversalis fascia approach or the preperitoneal space approach. There are few large sample, randomised controlled trials investigating the curative effects of the anterior transversalis fascia approach versus the preperitoneal space approach for inguinal hernia repair in patients in northern China. METHODS AND ANALYSIS: This will be a prospective, large sample, multicentre, randomised, controlled trial. Registration date is 1 December 2016. Actual study start date is 6 February 2017. Estimated study completion date is June 2020. A cohort of over 720 patients with inguinal hernias will be recruited from nine institutions in Liaoning Province, China. Patient randomisation will be stratified by centre to undergo inguinal hernia repair via the anterior transversalis fascia approach or the preperitoneal approach. Primary and secondary outcome assessments will be performed at baseline (prior to surgery), predischarge and at postoperative 1 week, 1 month, 3 months, 1 year and 2 years. The primary outcome is the incidence of postoperative chronic inguinal pain. The secondary outcome is postoperative complications (including rates of wound infection, haematoma, seroma and hernia recurrence). ETHICS AND DISSEMINATION: This trial will be conducted in accordance with the Declaration of Helsinki and supervised by the institutional review board of the Fourth Affiliated Hospital of China Medical University (approval number 2015-027). All patients will receive information about the trial in verbal and written forms and will give informed consent before enrolment. The results will be published in peer-reviewed journals or disseminated through conference presentations. TRIAL REGISTRATION NUMBER: NCT02984917; preresults.

Hemocoagulase agkistrodon-induced anaphylactic shock: A case report and literature review.

Hemocoagulase agkistrodon for injection is the national first-class new drug of China with good hemostatic function and safety for capillary hemorrhage in abdominal incision of surgical patients. Adverse drug reactions (ADRs) to hemocoagulase agkistrodon are rarely reported. In this paper, we describe a case of a 41-year-old woman who developed anaphylactic shock attributed to hemocoagulase agkistrodon before colon cancer surgery. Based on the Naranjo ADR probability score, a "probable" cause and effect relationship existed for this case. Although the cause of anaphylactic reaction (hemocoagulase or excipient) and exact mechanism of hemocoagulase agkistrodon-induced anaphylactic reaction are unknown, attention should be drawn to potential ADRs in clinical use.

Octupolar (C3 and S4) Symmetric Cyclized Indole Derivatives: Syntheses, Structures, and NLO Properties.

Several cyclized indole derivatives have been synthesized, and their structures been determined. The C3-symmetric single-chiral N-phenyltriindole (Tr-Ph3) crystallized in the P1 space group, and the S4-symmetric saddle-like tetraindole (TTr) crystallized in the I4̅ space group. The Tr-Ph3 and TTr crystals exhibit remarkable powder SHG intensities 5 and 11 times that of KH2PO4 (KDP), respectively. TTr is a useful octupolar core to build S4-symmetric molecules and crystals for second-NLO materials.

High expression of microRNA-130b correlates with poor prognosis of patients with hepatocellular carcinoma.

BACKGROUND: Whether microRNA-130b(miR-130b) can serve as a prognostic biomarker of hepatocellular carcinoma (HCC) has not been investigated. In the present study, we investigated the feasibility of miR-130b as a novel prognostic biomarker for HCC. METHODS: We retrospectively investigated 97 patients diagnosed with HCC who underwent routine curative surgery between May 2007 and July 2012. miR-130b expression in HCC tissues and paired normal adjacent liver tissues was measured by reverse transcription and real-time PCR (RT-PCR). Survival curves were plotted using the Kaplan-Meier method and differences in survival rates were analyzed using the log-rank test. RESULTS: miR-130b expression level was significantly higher in HCC tissues compared with normal adjacent liver tissues (P<0.0001). The 5-year overall survival (OS) of high miR-130b expression group was significantly shorter than that of low miR-130b expression group (43.6% vs. 71.5%; P=0.022). Moreover, the 5-year disease-free survival (DFS) of high miR-130b expression group was also significantly shorter than that of low miR-130b expression group (25.9% vs. 63.9%; P=0.012). In a multivariate Cox model, we found that miR-130b expression was an independent prognostic factor for both 5-year OS (hazards ratio [HR] =2.523, 95% confidence interval [CI] =1.024-7.901, P=0.011) and 5-year DFS (HR=4.003, CI=1.578-7.899, P=0.005) in HCC. CONCLUSION: The results indicated that high expression of microRNA-130b was correlated with significant characteristics of patients with HCC, and it might be useful as a novel prognostic biomarker for HCC. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_160.

miR-21 expression predicts prognosis in hepatocellular carcinoma.

PURPOSE: The aim was to investigate the expression level of miR-21 in HCC tissues and its prognostic value among Asian population. METHODS: In the present study, expression of miR-21 was evaluated by qRT- PCR in tumor and adjacent non-neoplastic tissues in 119 HCC patients. The association of miR-21 expression with clinicopathological factors and the prognosis of HCC patients was also analyzed. Survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. RESULTS: We found that miR-21 expression was significantly higher in HCC tissues compared with normal adjacent liver tissues (P<0.0001). The 5-year overall survival (OS) of high miR-21 expression group was significantly shorter than that of low miR-21 expression group (40.2% vs. 70.7%; P=0.007). Moreover, the 5-year disease-free survival (DFS) of high miR-21 expression group was also significantly shorter than that of low miR-21 expression group (17.4% vs. 57.3%; P=0.001). Furthermore, in a multivariate Cox model, we found that miR-21 expression was an independent poor prognostic factor for both 5-year OS (hazards ratio [HR]=3.189, 95% confidence interval [CI]=1.911-10.012, P=0.03) and 5-year DFS (HR=5.897, CI=3.009-13.763, P<0.001) in HCC. CONCLUSIONS: The results of the present study suggested miR-21 expression level could be a novel potential biomarker for HCC prognosis.

Profile of hepatitis B virus resistance mutations against nucleoside/nucleotide analogue treatment in Chinese patients with chronic hepatitis B.

AIM: Antiviral drug-resistant HBV mutants are complex and currently partly understood. This study was performed to analyze the profile of hepatitis B virus (HBV) resistance mutations against nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B (CHB). METHODS: This was a population-based cross-sectional study. Serum samples of 179 patients with virological breakthrough undergoing different NAs treatment were obtained between January 2008 and December 2012. The HBV reverse transcriptase region was sequenced and the following NAs-resistant changes including rtL80, rtI169, rtV173, rtL180, rtA181, rtT184, rtA194, rtS202, rtM204, rtN236 and rtM250 were analyzed. RESULTS: In this cohort, 21.2% (38/179) were genotypes B and 78.8% (141/179) were genotypes C; and 89.4% (160/179) of them detected NAs-resistant mutations. The prevalence of HBV mutations at rtM204 was 93.0% (106/114) in patients with lamivudine (LAM) or telbivudine (LdT)-based therapies, and that of rtN236 mutations was 76.1% (35/46) in patients with adefovir dipivoxil (ADV)-based therapies. Among LAM/LdT based therapies, HBV rtM204I was significantly associated with HBV rtL80I/V mutations [rtM204I+rtL80I/V (50.0%, 32/64) vs. rtM204V+rtL80I/V (27.3%,9/33), P=0.032]; while the HBV rtM204V mutations was significantly associated with HBV rtL180M mutations [rtM204V+rtL180M (100%, 33/33) vs. rtM204I+rtL180M (60.9%, 39/64), P<0.001]. Additionally, HBV rtA181 mutations were observed in 19.3% (22/114) of patients with LAM/LdT-based therapy and 23.9% (11/46) of patients with ADV-based therapy. CONCLUSIONS: Majority of virological breakthrough is associated with NAs-resistant HBV, and the mutation patterns of NAs-resistant HBV are complicated in real clinical practice.

Thermal ablation versus repeated hepatic resection for recurrent intrahepatic cholangiocarcinoma.

BACKGROUND: Repeated hepatic resection (HR) and thermal ablation therapy (TAT) are increasingly being used to treat recurrent intrahepatic cholangiocarcinoma (RICC). This study compared the efficacy and safety of these procedures for RICC treatment. METHODS: Patients were studied retrospectively after curative resection of RICCs by repeated HR (n = 32) or TAT (n = 77). Treatment effectiveness and prognosis were compared between the two treatment groups. RESULTS: The repeated HR and TAT groups did not differ in their overall survival (OS; p = 0.996) or disease-free survival (DFS; p = 0.692) rates. However, among patients with recurrent tumors >3 cm in diameter, patients in the repeated HR group had a higher OS rate than patients in the TAT group (p = 0.037). The number of recurrent tumors and the recurrence interval were significant prognostic factors for OS. The major complications incidence rate was greater in the repeated HR group than in the TAT group (p < 0.001). CONCLUSIONS: Repeated HR and TAT are both effective treatments for RICC with similar overall efficacies. TAT should be preferred in any cases when the RICC is ≤3 cm in diameter and technically feasible. However, for large tumors (>3 cm), repeated HR may be a better choice.

[Effect of electroacupuncture on the biochemical indices of bone and bone collagen metabolism and TNF-alpha in osteoporosis model rats without ovaries].

OBJECTIVE: To explore the mechanisms of electroacupuncture (EA) on postmenopausal osteoporosis (PMO). METHODS: Sixty female SD rats aged 6 months were selected, resected double ovaries and fed for 90 days in order to make the model of experimental osteoporosis, and then, they were randomly divided into a model control group (without any therapy), a routine acupoints applying group, which were treated with EA at "Pishu" (BL 20), "Weishu" (BL 21), "Shenshu" (BL 23) and "Qihaishu" (BL 24), and an EA with tonification method (EAT) group at "Guanyuan" (CV 4) and "Zusanli" (ST 36), and an EA with dispersing blood stasis method (EAD) group at "Shenshu" (BL 23), "Geshu" (BL 17) and "Dazhu" (BL 11), and an EA with tonification and dispersing blood stasis method (EATD) group at "Guanyuan" (CV 4), "Zusanli" (ST 36), "Shenshu" (BL 23), "Geshu" (BL 17) and "Dazhu" (BL 11), 12 rats in each group. EA therapy was performed once a day, 30 min each time. Then these rats rested for 1 day after consecutive treatment for 6 days. The treatment lasted for 12 weeks. Enzyme linked immunosorbent assay (ELISA) was used to examine the level of TNF-alpha, and the level of E2, osteocalin (BGP) and carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I lollagen (ICTP) by radioimmunoassay, and alkaline phosphatase by p-nitrophenylphosphate method, and Ca, P, Deoxypyridinoline (DPD) and creatinine (Cr) in urine were detected by automatic biochemistry analyzer. RESULTS: Compared with model control group, the level of DPD/Cr, Ca/Cr, and the serum contents of ALP, BGP, TNF-alpha and ICTP in all EA groups decreased significantly (all P < 0.01), the level of E2 and PICP in serum increased significantly (all P < 0.01). Compared with EATD group, the level of DPD/Cr and Ca/Cr in the other three EA groups had no statistical differences (all P > 0.05), but the level of ALP, BGP, TNF-alpha and ICTP in serum increased significantly (all P < 0.01), the level of E2 and PICP in serum decreased significantly (all P < 0.01). CONCLUSION: Acupuncture can reduce significantly the level of DPD/Cr, Ca/Cr, and the serum contents of ALP, BGP, TNF-alpha and ICTP, increase significantly the level of E2 and PICP in PMO model rats and EA with tonification and dispersing blood stasis method is superior significantly to the other routine acupuncture methods.