[Analysis of efficacy and factors influencing sequential combination therapy with tenofovir alafenamide fumarate after treatment with entecavir in chronic hepatitis B patients with low-level viremia].

Objective: To observe the efficacy and factors influencing sequential or combined tenofovir alafenamide fumarate (TAF) after treatment with entecavir (ETV) in patients with chronic hepatitis B (CHB) with low-level viremia (LLV). Methods: 126 CHB cases treated with ETV antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from January 2020-September 2022 were retrospectively collected. Patients were divided into a complete virologic response (CVR) group (n = 84) and a low-level viremia (LLV) group (n = 42) according to the HBV DNA level during treatment. Clinical characteristics and laboratory indicators of the two groups at baseline and 48 weeks were analyzed by univariate analysis. Patients in the LLV group were divided into three groups according to their continued antiviral treatment regimen until 96 weeks: continued use of ETV as a control group; replacement of TAF as a sequential group; and combination of ETV and TAF as a combined group. The data of the three groups of patients were analyzed by one-way analysis of variance for 48 weeks. HBV DNA negative conversion rate, HBeAg negative conversion rate, alanine aminotransferase (ALT), creatinine (Cr), and liver stiffness test (LSM) were compared among the three groups after 96 weeks of antiviral treatment. Multivariate logistic regression was used to analyze the independent factors influencing the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Receiver operating characteristic curve (ROC) was used to evaluate the effectiveness of predicting the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Kaplan-Meier was used to analyze the cumulative negative rate of DNA in LLV patients, and the Log-Rank test was used for comparison. HBV DNA and HBV DNA negative conversion rates during treatment were observed dynamically. Results: Univariate analysis showed statistically significant differences in age, BMI, HBeAg positivity rate, HBV DNA, HBsAg, ALT, AST, and LSM at baseline between the CVR group and the LLV group (P < 0.05). Univariate analysis of variance revealed no statistically significant difference among the three groups of LLV patients at 48 weeks (P > 0.05). HBV-DNA negative conversion rate in the sequential group and the combination group was significantly higher than that in the control group after 96 weeks of treatment (88.89% vs. 41.18%, 85.71% vs. 41.18%, χ (2) = 10.404, P = 0.006). HBeAg negative conversion rate was higher than that of the control group, with no statistically significant difference (P > 0.05).Compared with the control group, ALT, Cr, and LSM in the sequential group and the combined group were equally improved to varying degrees, with a statistically significant difference (P < 0.05). Subsequent use of ETV and HBV DNA at 48 weeks were independent risk factors for HBV DNA positivity at 96 weeks in LLV patients (P < 0.05). The AUC of HBV DNA at 48 weeks was 0.735 (95%CI: 0.578 ~ 0.891), the cut-off value was 2.63 log(10) IU/ml, and the sensitivity and specificity were 76.90% and 72.40%, respectively. DNA conversion rate was significantly lower in LLV patients receiving 48-week ETV and 48-week HBV DNA≥2.63 log10 IU/mL than in patients receiving sequential or combined TAF and 48-week HBV DNA < 2.63 log(10) IU/mL. HBV DNA negative conversion rates in the sequential group and combined group at 72 weeks, 84 weeks, and 96 weeks were higher than those in the control group during the period from 48 weeks to 96 weeks of continuous treatment, and the differences were statistically significant (P < 0.05). Conclusion: Sequential or combined TAF antiviral therapy could more effectively improve the 96-week CVR rate, as well as hepatic and renal function, and alleviate the degree of hepatic fibrosis in CHB patients with LLV following ETV treatment. Subsequent use of ETV and HBV DNA load at 48 weeks were independent predictors of HBV DNA positivity at 96 weeks in LLV patients.

[Correlation between serum interleukin-38 and acute exacerbation of chronic obstructive pulmonary disease with pulmonary embolism].

Objective: To investigate the correlation between serum interleukin-38 (IL-38) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with pulmonary embolism (PE). Methods: The 94 patients with AECOPD admitted to Tianjin Chest Hospital from August 2015 to April 2018 were suspected of PE. They were divided into two groups based on CT pulmonary angiography (CTPA) and color Doppler ultrasound of lower extremity veins: 39 cases in PE group and 55 cases in Non-PE group. The general data and laboratory examination results of these subjects were recorded. Serum IL-38 was measured by double antibody enzyme-linked immunosorbent assays (ELISA). The between-group differences of above parameters were analyzed. Pearson correlation or Spearman rank correlation was used to analyze the association of IL-38 with each variable in AECOPD patients. Binary Logistic regressions were conducted to determine the risk factors of AECOPD with PE. ROC curve was used to assess the value of serum IL-38 in predicting AECOPD with PE. Results: The serum level of IL-38 was lower in PE group than in Non-PE group [46.3 (33.1, 58.1) vs 61.5 (46.6, 72.5) ng/L, P<0.05]. Correlation analysis showed that serum IL-38 levels were negatively correlated with C reactive protein and fibrinogen in patients with AECOPD (r=-0.38,-0.29, all P<0.05). Binary Logistic regressions showed that lower serum IL-38 level was a risk factor of AECOPD with PE (OR=0.78, 95%CI: 0.61-0.94, P<0.05). The area under the ROC curve was 0.74 (95% CI: 0.63-0.84, P<0.05). When cutoff value of serum IL-38 was 52.1ng/L, the sensitivity was 70.9% and the specificity was 69.2% respectively. Conclusion: IL-38 could relieve the hypercoagulability by inhibiting inflammation in patients with AECOPD and could act as a predictor of AECOPD with PE.

[The expression of LINC00052 during glycidyl methacrylate-induced malignant transformation of 16HBE cells].

Objective: To investigate the expression and role of LINC00052 during glycidyl methacrylate (GMA) -induced malignant transformation of 16HBE cells. Methods: Human bronchial epithelial (16HBE) cells were divided into GMA transformation group and corresponding DMSO control group, and the 10th, 20th and 30th generation cells of each group were collected LncRNA microarrays were used to analysis expression of LINC00052 in different stage of malignant transformation. Bioinformatics analysis was applied and the relative expression of LINC00052 and its potentially target genes was detected by real-time quantification PCR (qPCR) . Results: The results of microarray analysis showed that LINC00052 was up-regulated by 1.32-fold, down-regulated by 1.64-fold and down-regulated by 4.92-fold in the malignant transformation early (P10) , middle term (P20) and late (P30) , respectively, The results of qPCR showed that compared with the DMSO control group, the expression of LINC00052 was up-regulated by 1.55 times, down-regulated by 1.20 times and down-regulated by 2.35 times in P10, P20 and P30, respectively, and the difference was statistically significant (P<0.05) . There was a statistically significant difference in the relative expression of NTRK3 between the GMA transformation group of P10 and P30 generations with the corresponding DMSO control group (P<0.05) . Conclusion: LINC00052 is highly expressed in early time of GMA-induced malignant transformation of 16HBE, and down-regulated in the middle and last stage of malignant transformation and may play a protective role in GMA-induced malignant transformation of 16HBE by influencing the expression of its target gene NTRK3.

[Interleukin-38 expression and clinical significance in serum of patients with chronic obstructive pulmonary disease].

Objective: To investigate the serum level of interleukin-38 (IL-38) and its clinical significance in patients with chronic obstructive pulmonary disease (COPD). Methods: Totally 72 patients with acute exacerbation of COPD (AECOPD group) and 65 patients with stable COPD (S-COPD group) were recruited from Tianjin Chest Hospital from June 2016 to August 2017. In the same period 40 elderly healthy subjects were selected as control group (C group). The general data and laboratory examination results of these subjects were recorded. Serum IL-38 was measured by double antibody enzyme-linked immunosorbent assays (ELISA). The inter-group differences of above parameters were analyzed. Pearson correlation or Spearman rank correlation analysis was used to analyze the correlation between IL-38 and each variable, and multivariate stepwise regression analysis was used to determine the influencing factors of serum IL-38 in COPD patients. Results: The serum level of IL-38 was higher in AECOPD group than in S-COPD group[(57.88±13.72) vs (51.75±14.06) ng/L, P<0.05], and was higher in either of the two COPD groups than in C group[(46.37±13.18) ng/L](both P<0.05). Correlation analysis of single factor showed that serum IL-38 levels were positively correlated with body mass index (r=0.190, P<0.05), and negatively correlated with C reactive protein (CRP), fibrinogen (FIB), forced expiratory volume in one second as a percentage of estimated value (FEV1%pred) and the number of acute exacerbations in the past 1 year (r=-0.344, -0.176, -0.195, -0.229, all P<0.05). The CRP level and the number of acute exacerbations in the past 1 year were independent factors affecting the serum level of IL-38 (ß=-0.204, -0.183, both P<0.05) in patients with COPD. Conclusion: IL-38 is compensatory increased in serum of patients with COPD and may be used as one of the serological markers for evaluation of COPD.

In vitro and in vivo evidence for anti-inflammatory properties of 2-methoxyestradiol.

2-Methoxyestradiol (2MEO) is an endogenous metabolite of 17ß-estradiol that interacts with estrogen receptors and microtubules. It has acute anti-inflammatory activity in animal models that is not attributable to known antiproliferative or antiangiogenic actions. Because macrophages are central to the innate inflammatory response, we examined whether suppression of macrophage activation by 2MEO could account for some of its anti-inflammatory effects. Inflammatory mediator production stimulated by lipopolysaccharide (LPS) and interferon-γ in the J774 murine macrophage cell line or human monocytes was measured after treatment with 2MEO or the anti-inflammatory agent dexamethasone. The effect of these agents on LPS-induced acute lung inflammation in mice was also examined. 2MEO suppressed J774 macrophage interleukin-6 and prostaglandin E2 production (by 30 and 47%, respectively, at 10 µM) and human monocyte tumor necrosis factor-α production (by 60% at 3 µM). Estradiol had no effect on J774 macrophage activation, nor did the estrogen receptor antagonist 7α-[9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17ß-diol (ICI 182,780) prevent the effects of 2MEO. The actions of 2MEO were not mimicked by the microtubule-interfering agents colchicine or paclitaxel. In mice exposed to LPS, bronchoalveolar lavage protein content, a measure of vascular leak and epithelial injury, was reduced to a comparable extent (~54%) by treatment with 2MEO (150 mg · kg⁻¹) or dexamethasone (1 mg · kg⁻¹). In addition, 2MEO reduced LPS-induced interleukin-6 gene expression. Thus, 2MEO modulates macrophage activation in vitro and has high-dose acute anti-inflammatory activity in vivo. These findings are consistent with the acute anti-inflammatory actions of 2MEO being mediated in part by the suppression of macrophage activation.

A distribution-moment model of energetics in skeletal muscle.

In this paper we develop a theory for calculating the chemical energy liberation and heat production of a skeletal muscle subjected to an arbitrary history of stimulation, loading, and length variation. This theory is based on and complements the distribution-moment (DM) model of muscle [Zahalak and Ma, J. biomech. Engng 112, 52-62 (1990)]. The DM model is a mathematical approximation of the A. F. Huxley cross-bridge theory and represents a muscle in terms of five (normalized) state variables: A, the muscle length, c, the sarcoplasmic free calcium concentration, and Q0, Q1, Q2, the first three moments of the actin-myosin bond-distribution function (which, respectively, have macroscopic interpretations as the muscle stiffness, force, and elastic energy stored in the contractile tissue). From this model are derived two equations which predict the chemical energy liberation and heat production rates in terms of the five DM state variables, and which take account of the following factors: (1) phosphocreatine hydrolysis associated with cross-bridge cycling; (2) phosphocreatine hydrolysis associated with sarcoplasmic-reticulum pumping of calcium; (3) passive calcium flux across the sarcoplasmic-reticulum membrane; (4) calcium-troponin bonding; (5) cross-bridge bonding at zero strain; (6) cross-bridge strain energy; (7) tendon strain energy; and (8) external work. Using estimated parameters appropriate for a frog sartorius at 0 degree C, the energy rates are calculated for several experiments reported in the literature, and reasonable agreement is found between our model and the measurements. (The selected experiments are confined to the plateau of the isometric length-tension curve, although our theory admits arbitrary length variations.) The two most important contributions to the energy rates are phosphocreatine hydrolysis associated with cross-bridge cycling and with sarcoplasmic-reticulum calcium pumping, and these two contributions are approximately equal under tetanic, isometric, steady-state conditions. The contribution of the calcium flux across the electrochemical potential gradient at the sarcoplasmic-reticulum membrane was found to be small under all conditions examined, and can be neglected. Long-term fatigue and oxidative recovery effects are not included in this theory. Also not included is the so-called 'unexplained energy' presumably associated with reactions which have not yet been identified. Within these limitations our model defines clear quantitative interrelations between the activation, mechanics, and energetics in muscle, and permits rational estimates of the energy production to be calculated for arbitrary programs of muscular work.

The mechanical response of the active human triceps brachii muscle to very rapid stretch and shortening.

Very rapid, small amplitude, ramp-and-hold rotations were imposed on the braced forearms of three normal adult male subjects who were isometrically contracting their elbow extensors. By carefully accounting for inertial and viscoelastic coupling effects in the experimental system it was possible to compute the time course of the muscle-moment evoked by these mechanical perturbations. The muscle-moment responses, and their dependence on rotation amplitude and direction, as well as tonic contraction level, are described. These responses are also compared to the predictions of a simple muscle model which we have proposed previously on the basis of frequency-response tests. The results indicate that: at a given tonic contraction level, triceps may be stiffer in an isometric state than in an oscillatory steady state, and high frequency fluctuations in the myoelectric activity are very ineffective in generating corresponding muscle-force fluctuations.

[Effect of qidan tongmai tablet on glucose and lipid metabolism in patients with diabetes mellitus type 2].

OBJECTIVE: To study the effect of Qidan Tongmai tablet (QDTMT) on glucose and lipid metabolism in patients with diabetes mellitus (DM) type 2. METHODS: Patients of DM, with or without hyperlipidemia complication (HLC) were divided into 4 groups, Group A (33 cases without HLC) and B (33 cases with HLC) were treated by QDTMT, Group C (31 cases without HLC) and D (31 cases with HLC) were not treated by QDTMT. The treatment was carried out on the previous basic hypoglycemic treatment with a therapeutic course of 2 months. RESULTS: The levels of fasting glucose, 2 hrs postprandial blood glucose and glycosylated hemoglobin, as well as the levels of total cholesterol and triglyceride lowered, and the high density lipoprotein increased in Group A and B after treatment, as compared with those before treatment, the difference was significant (P < 0.01). While in Group C and D, the above-mentioned indexes were not changed significantly (P > 0.05). No apparent side-effect was found in the QDTMT treatment period. CONCLUSION: Besides regulating abnormal blood lipid, QDTMT has also a hypoglycemic effect in certain degree in patients with DM type 2.

[Immunologic inhibition and anti-allergic action of Cryptotympana atrata Fabricius].

Cryptoympana atrata Fabricius(CAF)ig 5g/kg in mice decreases weights of the spleen and thymus, markedly decreases the clearance rate of iv charcoal particles and significantly inhibits the phagocytosis of peritoneal macrophages of mice. CAF ig at the above doses markedly suppresses IgE antibody mediated reactions, heterologous passive cutaneous anaphylaxis (PCA) in mice, degranulation of mast cells of calvarial periosteum in rats, and the delayed hypersensitivity reaction of ear induced by DNCB in mice.

[Determination of notoginsenoside R1 in radix notoginseng by HPLC-ELSD].

OBJECTIVE: To establish a method for the determination of notoginsenoside R1 in Radix Notoginseng. METHOD: The HPLC-ELSD method was used for the determination. Chromatographic conditions: Shimpack CLC-ODS column(6.0 mm x 150 mm), acetonitrile-water(30:70) as the mobile phase, and Shimadzu LC-6A with SEDEX 55 ELSD detector. RESULT: The recovery rate is 101.57% and relative standard deviation 1.98%. CONCLUSION: The method is reliable for the quality control of Radix Notoginseng.

Muscle activation and contraction: constitutive relations based directly on cross-bridge kinetics.

This paper reviews recent work aimed at deriving tractable constitutive relations for skeletal muscle from biophysical cross-bridge theories. Discussion is focused on a model proposed previously by the first author (the Distribution-Moment Model), which emphasizes the important role of the moments of the actin-myosin bond-distribution function. The theory leads to a relatively simple third order state variable model for contraction dynamics in which the state variables are the three lowest order moments of the bond-distribution function; further, these three moments have simple macroscopic interpretations as muscle stiffness, force, and elastic energy. New results are presented on the formulation of a compatible model for excitation-contraction coupling, and this model requires the introduction of only one more state variable--the free calcium concentration.

Molecular epidemiology of Japanese encephalitis virus in Okinawa.

In order to elucidate the molecular characteristics of Japanese encephalitis (JE) virus in Okinawa, 23 strains of JE virus isolated in a 25-year span were sequenced for the 240 nucleotides of the C-preM junction region and 111 nucleotides of the E gene region and compared with those of reference strains isolated in mainland Japan. The results of phylogenic analysis showed that although all the Okinawan isolates showed more than 96% homology in the nucleotide sequence in each region, they were chronologically divided into two groups: the old group (nine strains) and a new group (14 strains). On the other hand, in a comparison with reference strains in mainland Japan, the Okinawan isolates showed more than 94% nucleotide sequence homology in both regions, indicating that the Okinawan strains belong to the same genotype as that of JE strains in mainland Japan. The nucleotide homology of the old group was relatively higher than that of the new group. Among the 14 strains in the new group, 13 strains were isolated from mosquitoes collected from a pig farm from 1986 through 1992. These strains showed higher nucleotide divergence than the old group strains, isolated from mosquitoes and swine sera collected at several sites, in both regions. A nucleotide substitution at the position 1920 in the E gene was identified in three isolates. This substitution generated an aspargine-proline-threonine sequence capable of serving as an attachment site of carbohydrate.

Detection of dengue 4 virus core protein in the nucleus. II. Antibody against dengue 4 core protein produced by a recombinant baculovirus reacts with the antigen in the nucleus.

The dengue 4 virus (DEN-4) core gene and part of the PreM genes were inserted into the baculovirus polyhedrin gene region. The recombinant baculovirus directed the synthesis of the DEN-4 core protein fused to a part of the polyhedrin protein (Mr 25K), as determined by Western blot analysis using DEN-4 core monoclonal antibody. A mouse polyclonal antibody prepared against the DEN-4 core fusion protein showed antigenic reactivity with the authentic DEN-4 core protein (Mr 15.5K) present in the nucleus as well as in the cytoplasm of DEN-4-infected Vero cells as demonstrated by the peroxidase-antiperoxidase staining method. This antibody did not react with cells infected with DEN-1, -2, -3 or Japanese encephalitis virus, or mock-infected cells.

Hepatitis delta virus genotype IIb predominates in an endemic area, Okinawa, Japan.

Hepatitis delta virus (HDV) infection is relatively common in the Miyako Islands, Okinawa, Japan, where the infection has been reported to be associated with low pathogenicity. HDV RNA extracted from each of 6 patients with HDV-related chronic liver disease living in the islands was amplified by reverse transcription-polymerase chain reaction and examined genetically to determine the HDV genotype. All isolates from the 6 patients were classified as genotype II by the neighbor-joining method. However, these isolates had relatively low homology (75-81%) to the HDV genotype II isolate reported from Japan, and showed relatively high identity (83-95%) to the novel genotype II isolate (HDV genotype IIb) recently reported from Taiwan. Phylogenetic analysis showed that the 6 isolates form a novel group within HDV genotype II. Furthermore, there was notable variation in sequence among the 6 isolates compared with the relatively close clustering of HDV isolates within limited areas (e.g., United States, Archangelos, Turkey, Albania, Peru). HDV genotype II in the Miyako Islands is therefore unique, and HDV infection may have been introduced at a relatively early time in this area.