[Study on early predictive factors of an incomplete viral response with 48 week-entecavir therapy in HBeAg-positive chronic hepatitis B patients].

Objective: To study the virological and serological indicators before treatment and 24 weeks after treatment to predict the partial virological response (PVR) of 48-week entecavir (ETV) treatment, and formulate early clinical adjustment treatment plans for HBeAg-positive CHB patients. Methods: HBeAg-positive CHB-naïve patients diagnosed in the Department of Infectious Diseases, Shengjing Hospital, China Medical University, who were treated with oral ETV monotherapy from January 2018 were enrolled. The groups were divided according to the test results of HBV DNA at 48 weeks. Among them, HBV DNA < 20 IU/ml was the complete viral response (CVR) group, and HBV DNA ≥ 20 IU/ml was the PVR group. The virological and serological indexes of the two groups before treatment and 24 weeks after treatment were compared. ROC curve univariate analysis and multivariate logistic regression were performed to find out the early predictors of PVR in HBeAg-positive CHB patients receiving ETV therapy for 48 weeks. Results: As of July 2020, a total of 90 cases had completed 48 weeks of treatment, including 50 cases of CVR (55.56%) and 40 cases of PVR (44.44%). Before treatment and at 24 weeks of treatment, HBsAg, HBeAg and HBV DNA in the PVR group were significantly higher than those in the CVR group (P < 0.001). Univariate analysis showed that HBV DNA quantification (AUC = 0.961, P < 0.001, PPV = 97.06%, NPV = 87.50%) and HBeAg quantification (AUC = 0.883, P < 0.001, PPV = 90.63%, NPV = 81.03%) had higher predictive value at 24 weeks of treatment. Multivariate analysis showed that HBeAg > 1.952 log(10) S/CO (OR = 3.177, 95% CI: 1.261 ~ 8.267, P = 0.018) and HBV DNA > 2.205 log(10) IU / ml (OR = 43.197, 95% CI: 6.858 ~ 272.069, P < 0.001) were independent predictors of PVR at 24 weeks of treatment, and their combination had the best predictive effect. Conclusion: In HBeAg-positive CHB patients receiving ETV treatment for 48 weeks, HBV DNA combined with HBeAg quantification can be an early predictor of PVR at 24 weeks. Additionally, patients with both HBV DNA and HBeAg > 2 log(10) at 24 weeks of treatment must wait 48 weeks to obtain CVR, so it is recommended that treatment strategies should be adjusted at this time.

Effect of low temperatures on BAX and BCL2 proteins in rats with spinal cord ischemia reperfusion injury.

We evaluated changes in BAX and BCL2 expression levels after spinal cord ischemia/reperfusion injury (SCII) and hypothermia during operations in rats. Eighty rats were divided into four groups: Group A (N = 20, 18°C); Group B (N = 20, 28°C); Group C (N = 20, room temperature); and Group D (N = 20, sham operation control). Spinal cord ischemia was induced for 90 min. Hypothermia was induced 15 min before, and maintained during ischemia, followed by heating to normothermia for 30 min after reperfusion. Motor function of the lower limbs was evaluated according to the Tarlov score at 72 and 168 h. For each rat, spinal cord samples were taken at 6, 24, 72 h, and 1 week to evaluate the histopathological changes, neuronal apoptosis, and BAX and BCL2 expression levels. Compared with normothermia, hypothermia significantly improved hind limb function; Group B achieved a higher score than Group A. Group D showed no neurologic deficiency, while the other groups showed various degrees. Group C exhibited greater neuronal apoptosis, higher BAX expression, but lower BCL2 expression than the other groups. Compared with Group A, BAX was expressed less and BCL2 more in Group B, and there was less apoptosis in Group B. Hypothermia preserves hind limb motor function and reduces neuronal death, thereby protecting rats from SCII. The spinal cord may be protected from SCII by inhibition of BAX and activation of BCL2. However, deep hypothermia may inhibit the expression of BCL2, resulting in a worse outcome than mild hypothermia.

[Inflammatory factors in periodontitis patients and their effects toward the occurrence of gestational diabetes mellitus: a case-control study].

Objective: To explore the effects of periodontitis and inflammatory factors toward the occurrence of gestational diabetes mellitus (GDM). Methods: Pregnant women who came to the Department of Obstetrics, Northwest Women's and Children's Hospital for prenatal examinations during March to November of 2021 were invited to participate in this study. Participants with GDM who met the inclusion criteria (n=100) were assigned into the case group; while healthy participants (n=100) were assigned into the control group. Information of participants from the two groups were collected by questionnaires and periodontal statuses were clinically recorded in the meantime. Gingival crevicular fluid (GCF) and venous blood were also collected from participants of two groups to analyze the expression levels of inflammatory factors like C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, IL-8, IL-10 and IL-33. Factors different between the two groups were included in the multivariate regression analysis model to determine the risk factors of GDM. Results: The age of participants was (33.4±5.1) years in case group and (30.5±4.5) years in control group respectively, which had statistical differences (t=4.33,P<0.001). Besides, the body mass index of participants from case group was also significantly higher than control group [(28.11±3.85) kg/m2 vs. (23.31±3.15) kg/m2, t=9.65, P<0.001]. Participants with GDM had more adverse periodontal clinical parameters. Prevalence of periodontitis in GDM group was 47.0% (47/100) compared with 29.0% (29/100) in control group (χ²=6.88, P=0.009). Multivariate regression analysis results indicated that periodontitis was a critical risk factor for the occurrence of GDM (OR=1.882, P<0.001). Besides, GCF IL-8, serum TNF-α, IL-8 and IL-10 were also risk factors of GDM due to their higher expressions. Among them, TNF-α in serum (OR=2.077) and IL-8 in serum (OR=2.060) had more significant impacts (P<0.001). Conclusions: This study demonstrated that periodontitis was associated with the occurrence of GDM. Up-regulation of serum pro-inflammatory mediators leaded by local periodontal inflammatory microenvironment might play a critical role in this pathological process.

[Research progress in the association of periodontitis and gestational diabetes mellitus].

Periodontitis is the main cause of adult tooth loss, which seriously affects oral health and acts as a high-risk factor for varieties of systemic diseases. Gestational diabetes mellitus (GDM) is defined as glucose intolerance occurred or firstly identified during pregnancy. Prevalence of GDM is increasing over the past years worldwide. Besides adverse effects toward maternal and infant health in perinatal period, GDM also has long-term effects. Current studies have demonstrated that there is a bidirectional relationship between periodontitis and diabetes; however, the exact relationship between periodontitis and GDM remains elusive. In this paper, first reviewed the clinical association of periodontitis and GDM, and then discussed the underlying mechanisms of the two diseases, finally summarized the positive effect of periodontal therapy in controlling GDM. This paper will provide theoretical basis for the prevention diagnosis and therapy for the related diseases, promoting the maternal and infant health.

Exosomes derived from Taxol-resistant nasopharyngeal carcinoma (NPC) cells transferred DDX53 to NPC cells and promoted cancer resistance to Taxol.

OBJECTIVE: Nasopharyngeal carcinoma (NPC) is a common cancer with high incidence in Southern China. Taxol is one of the first-line chemotherapeutic drugs for treating NPC; however, Taxol resistance has become the main difficulty for clinical treatment and the mechanisms remain not fully understood. In this study, we mainly focus on exploring whether exosomes from Taxol-resistant NPC cells played some roles in the resistance and progression of NPC. MATERIALS AND METHODS: Taxol was used to treat NPC cell line CNE1 and Taxol-resistant NPC cell line CNE1-TR cells to measure cell viability and IC50 by CCK-8 assay. Exosomes from these two cells were extracted and identified by transmission electron microscopy (TEM), and special protein markers were determined by Western blot (WB) assay. Real-time PCR was performed to detect levels of mRNAs in exosomes, CNE1 and CNE1-TR cells. WB was performed to detect protein levels. The p-DDX53 and si-DDX53 were constructed and cloned into cells, resulted with DDX53 overexpression and inhibition, then resistant associated protein levels and IC50 were measured. Finally, GW4869, an inhibitor to block exosome secretion, was used to verify that the exosomes derived from CNE1-TR cells transferred DDX53 to CNE1 cells and contributed to promote NPC resistance. RESULTS: We found that the IC50 to Taxolin CNE1-TR was much higher than that in CNE1 cells and DDX53 was highly expressed in Taxol-resistant CNE1-TR cells. Furthermore, exosomes were successfully extracted and determined, showing high levels of DDX53 and MDR1. Thus, they could promote cell resistance for CNE1 after adding CNE1-TR exosomes into CNE1 cells. Moreover, DDX53 overexpression increased the IC50 and upregulated MDR1 in CNE1 cells, while DDX53 inhibition showed the opposite results. In addition, the DDX53 inhibition decreased the IC50 and repressed MDR1 in CNE1-TR cells. Besides, blocking exosome released from CNE1-TR by using GW4869 treatment significantly repressed the levels of DDX53 and MDR1, and the IC50 of CNE1 cells was reversed. Finally, the increased levels of MDR1 were significantly reversed following with adding DDX53 si-DDX53-CNE1-TR exosomes, and the increased IC50 to Taxol was obviously reversed. CONCLUSIONS: This study firstly discovered that DDX53 was highly expressed in Taxol-resistant NPC cells, which could be transferred into normal NPC cells via exosome secretion. The transferred DDX53 could upregulate the expression of MDR1 in NPC cells to promote the resistant capacity to Taxol, which provided a novel insight for understanding NPC and might be a potential therapeutic target for NPC.

Acupuncture mechanisms in rabbits studied with microinjection of antibodies against beta-endorphin, enkephalin and substance P.

Injection of protein-A purified antibodies against Met-enkephalin and beta-endorphin into the periaqueductal gray matter (PAG) was shown to decrease the analgesic effect of electroacupuncture (EA) in rabbits. Met-enkephalin antibodies were more potent than the beta-endorphin antibodies in causing a statistically-significant effect on electroacupuncture analgesia. Antibodies to Met-enkephalin were also active at the spinal level, whereas antibodies against beta-endorphin were without effect: this is in agreement with a rich enkephalinergic innervation and absence of beta-endorphin-containing fibres in the spinal cord. Substance P, the other neuropeptide of this study, also seems to be important in mediating effects of electroacupuncture. Injection of antibodies into the periaqueductal gray caused decrease of the effect of electroacupuncture whereas intrathecal administration of Fab-fragment substance P antibodies caused a marked potentiation. The demonstration of site specificity of the neuropeptides in mediating analgesia induced by electroacupuncture supports the validity of this experimental approach.

Studies on the mesolimbic loop of antinociception--II. A serotonin-enkephalin interaction in the nucleus accumbens.

In a previous report we have shown that the antinociceptive effect elicited by microinjection of morphine into the periaqueductal gray is due, at least in part, to the activation of an ascending serotonergic pathway which releases 5-hydroxytryptamine in the nucleus accumbens. We now report that antinociception induced by intra-periaqueductal gray injection of morphine can be attenuated also by the narcotic antagonist naloxone or the enkephalin antibodies administered into the nucleus accumbens, and potentiated by D-phenylalanine, a putative inhibitor of the degradation of enkephalins. Moreover, the antinociceptive effect induced by 5-hydroxytryptamine administered into nucleus accumbens could be blocked by naloxone injected into the same site, whereas the antinociception elicited by intra-accumbens injection of [D-Ala2,D-Leu5]enkephalin was not affected by cinanserin, a 5-hydroxytryptamine blocking agent. It is concluded that morphine administered to the periaqueductal gray is capable of activating an ascending serotonergic pathway to release 5-hydroxytryptamine in the nucleus accumbens, which in turn activates an enkephalinergic mechanism within the same nucleus, resulting in an antinociceptive effect.

Hormonal control of Leydig cell differentiation.

Leydig cell progenitors contain significant concentrations of androgen receptors. When the metabolism of DHT to 3 alpha-DIOL is blocked, DHT stimulates testosterone production by Leydig cell progenitors, most probably via an androgen receptor dependent mechanism. Rapid metabolism by 3 alpha-HSD may limit the potency of exogenous DHT to stimulate differentiation of Leydig cell progenitors in vitro. Insulin-like growth factor-I enhances androgen production by purified immature Leydig cells. The elevated sensitivity of immature Leydig cells versus adult Leydig cells to IGF-I stimulation indicates that this peptide hormone has a role in their differentiation during puberty.

Met-enkephalin-Arg6-Phe7-like immunoreactive substances mediate electroacupuncture analgesia in the periaqueductal gray of the rabbit.

The present study was undertaken to investigate whether the C-terminal extended Met-enkephalin heptapeptide (Met-enkephalin-Arg6-Phe7, MEAP) played a role in mediating the analgesic effect of electroacupuncture in rabbits. MEAP and its degrading enzyme inhibitor captopril as well as antiserum against MEAP were injected into the periaqueductal gray (PAG) via a previously implanted cannula. Their effects on nociception were tested by the escape response latency (ERL) elicited by radiant heat applied on the skin of the snout. (1) Microinjection of MEAP (30-240 nmol) into PAG produced a dose-dependent analgesic effect which was 2.5 times more potent than Met-enkephalin (MEK) and 3 times less potent than morphine. The complete reversal of the analgesia elicited by 240 nmol of MEAP by a small dose of naloxone (0.1 mg/kg, i.v.) indicates that the effect of MEAP is mediated by naloxone sensitive opioid receptors. (2) In rabbits, a dose-dependent analgesia was elicited by an intra-PAG injection of captopril (60-240 nmol). A single dose of 240 nmol captopril increased ERL by more than 100%. This effect could be reversed by 30 nmol of naloxone injected into the same site, or by antiserum recognizing MEAP (1 microliter, titer 1:1500) but not by antiserum recognizing MEK (1 microliter, 1:8000) suggesting that captopril was able to protect MEAP from degradation. (3) Intra-PAG injection of 60 nmol of captopril significantly potentiated the after effect of electroacupuncture (EA) induced analgesia. This effect could be blocked either by 30 nmol (but not 7.5 nmol) of naloxone, or by 1 microliter (but not 0.1 microliter) of MEAP antiserum.(ABSTRACT TRUNCATED AT 250 WORDS)

Electroacupuncture and morphine analgesia potentiated by bestatin and thiorphan administered to the nucleus accumbens of the rabbit.

The endogenous opioid peptide enkephalin (EK) is known to be degraded mainly by two enzymes, the dipeptidyl carboxypeptidase 'enkephalinase' and aminopeptidase. Microinjection of the enkephalinase inhibitor thiorphan or the aminopeptidase inhibitor bestatin into the nucleus accumbens of the rabbit produced a dose-dependent analgesic effect. This analgesic effect was totally reversed by the narcotic antagonist naloxone or by antibodies against [Met5]enkephalin (MEK) administered to the same site. Antibodies against [Leu5]enkephalin were not effective. Moreover, microinjection of thiorphan or bestatin into the nucleus accumbens resulted in a marked potentiation of the aftereffect of electroacupuncture (EA) produced analgesia, as well as the analgesia induced by a small dose of morphine. It is concluded that the analgesic effect elicited by EA and morphine is mediated, at least in part, by MEK-like immunoreactive substance(s) in the nucleus accumbens.

A study of the effect of B-EP and naloxone on the function of the hypothalamo-pituitary-testicular axis of the rat.

To investigate whether endogenous opioid peptides (EOP) play an important role in intragonadal regulation of testicular function and regulation of the hypothalamic-pituitary-gonadal axis of the male rat, the authors employed two principal methods: culture of testicular Leydig cells and Sertoli cells, and in vitro perifusion of hypothalamo-pituitary Leydig cells of the adult rat. The results demonstrated that incubation of Leydig cells with B-endorphin (B-EP 10(-9) = 10(-6) mol/L) or naloxone (NAL 10(-5) = 10(-8) mol/L) manifested no significant changes of non-stimulated or hCG-stimulated testosterone secretion both in 20 and 60 day-old rats. Similar results were obtained when the cells were treated with B-EP (10(-10) = 10(-7) mol/L) for 48 h during culture. Pretreatment of incubated Leydig cells with B-EP in similar concentrations for 48 h showed no effect on the response to hCG stimulation. In addition, treatment with B-EP in vitro for 24 or 72 h manifested no effects on estradiol production by aromatization of cultured Sertoli cells. Neither NAL 10(-5) given in vitro nor NAL (5 mg/body weight) injected subcutaneously 1 h before decapitation affected LH and testosterone release from the perifused hypothalamo-pituitary Leydig cells system. These results could not support the hypothesis that B-EP is a local regulator of testicular function. The physiological significance of EOP in regulating the function of gonadal axis of adult male rat remains to be investigated further.

National food contamination monitoring programmes-levels of mercury, lead and cadmium in Chinese foods.

Six hundred and thirty-four food samples of six kinds were collected from Beijing, Shanghai, Jiangsu, Sichuan, Jilin and Guangdong areas, China and Hg, Pb, Cd contents were determined. The results showed that their levels in the Chinese foods were low; their levels in meat, egg, milk and fish were generally below the national hygienic standard. The average daily dietary intake of Hg, Pb, Cd were 7.25 micrograms, 103.77 micrograms and 30.72 micrograms respectively and they were all less than the ADI established by WHO.

Central neurotransmitters and acupuncture analgesia.

The role played by central neurotransmitters in acupuncture analgesia was evaluated by correlating neurochemical changes in central nervous system with the acupuncture effect, as well as modification of the acupuncture effects by pharmacological manipulations of central neurotransmitters. The results of experimental studies which were performed mainly on rats and rabbits indicated that central serotonin and endogenous opiate-like substances (OLS) seem to be the most important substrates for mediation of acupuncture analgesia while central catecholamines, especially norepinephrine through alpha receptors, may exert an antagonistic effect. It was also found that prolonged and repeated acupuncture resulted in a gradual decrease of the acupuncture effects. The development of some endogenous anti-opiate substrates (AOS) in central nervous system was tentatively implicated.

[Antagonism of morphine analgesia and electroacupuncture analgesia by cholecystokinin octapeptide (CCK-8) administered in periaqueductal gray (PAG) of the rabbits].

We have reported that intracerebroventricular (i. c. v.) injection of 1-4 ng of CCK-8 to the rat produced a remarkable antagonistic effect on morphine analgesia. In order to study the species specificity and the site of action, CCK-8 was microinjected into the PAG of the rabbit, and its influence on morphine analgesia and electroacupuncture analgesia was observed. The latency of the escape response (ERL) to radiant heat focused on the snout was measured as an index of the pain threshold. Microinjections were made via cannulae chronically implanted into the PAG. The drug solutions were delivered in a volume of 1 microliter, at a speed of 0.125 microliter/min. The ERL was measured for a period of 60 or 70 minutes at 10 min intervals. 1. CCK-8 administered unilaterally to the PAG of the rabbit at a dose of 3 ng antagonized the analgesia induced by morphine (4 mg/kg, i. v.) by 73% (P less than 0.001), and reduced the analgesic effect of electroacupuncture by 67% (P less than 0.001). These effects were dose-dependent within the range from 1.5 ng to 6.0 ng. The effect of CCK-8 was reversed by CCK receptor blocker proglumide (4 microliters, intra-PAG injection). Unsulfated CCK-8 (CCK-us) had no effect in this regard. These results indicate that in the PAG of the rabbit, exogenously administered CCK-8 was capable of antagonizing opioid analgesia by the activation of CCK receptors. 2. Two groups of rabbits were given with morphine (2 mg/kg, i. v.) and simultaneous injection of CCK-8 antiserum (CCK-AS, 1 microliter) or normal rabbit serum (NRS) into the PAG.(ABSTRACT TRUNCATED AT 250 WORDS)

Photodegradation of alpha-naphthaleneacetic acid in aqueous solution.

Kinetic processes of alpha-naphthaleneacetic acid (NAA) photolysis were studied under different conditions. The results showed that the ultraviolet light was more effective than fluorescent light in promoting degradation, and the degradation of NAA under ultraviolet light followed the first order kinetics with the photolysis rate constant of 1.15 x 10(-2) min-1 and half-life time (t1/2) of 60 min. Further, it was proved that the photolysis rate was higher in the presence of oxygen, titanium dioxide (TiO2), and low pH (acidic solution). At last, two photolysis intermediates were identified by GC-MS and possible photolysis pathways were proposed.

Raman spectroscopic determination of the length, strength, compressibility, Debye temperature, elasticity, and force constant of the C-C bond in graphene.

From the perspective of bond relaxation and bond vibration, we have formulated the Raman phonon relaxation of graphene, under the stimuli of the number-of-layers, the uni-axial strain, the pressure, and the temperature, in terms of the response of the length and strength of the representative bond of the entire specimen to the applied stimuli. Theoretical unification of the measurements clarifies that: (i) the opposite trends of the Raman shifts, which are due to the number-of-layers reduction, of the G-peak shift and arises from the vibration of a pair of atoms, while the D- and the 2D-peak shifts involve the z-neighbor of a specific atom; (ii) the tensile strain-induced phonon softening and phonon-band splitting arise from the asymmetric response of the C(3v) bond geometry to the C(2v) uni-axial bond elongation; (iii) the thermal softening of the phonons originates from bond expansion and weakening; and (iv) the pressure stiffening of the phonons results from bond compression and work hardening. Reproduction of the measurements has led to quantitative information about the referential frequencies from which the Raman frequencies shift as well as the length, energy, force constant, Debye temperature, compressibility and elastic modulus of the C-C bond in graphene, which is of instrumental importance in the understanding of the unusual behavior of graphene.

Correlation between the band gap, elastic modulus, Raman shift and melting point of CdS, ZnS, and CdSe semiconductors and their size dependency.

With structural miniaturization down to the nanoscale, the detectable quantities of solid materials no longer remain constant but become tunable. For the II-VI semiconductors example, the band gap expands, the elastic modulus increases, the melting point drops, and the Raman optical phonons experience red shift associated with creation of low frequency Raman acoustic modes that undergo blue shift with decreasing the dimensional scale. In order to understand the common origin of the size dependency of these seemingly irrelevant properties, we formulated these quantities for CdS, ZnS, and CdSe semiconductors from the perspectives of bond order-length-strength correlation and the local bond averaging approach. Consistency between the theory predictions and the measured size dependence of these quantities clarified that the undercoordination-induced local strain and quantum entrapment and the varied fraction of undercoordinated atoms of the entire solid correlate these quantities and dominate their size effect.

Mechanically stiffened and thermally softened Raman modes of ZnO crystal.

An analytical form connecting the energy shift of Raman modes directly to the bonding identities (order, nature, length, energy) of a specimen and the response of the bonding identities to the applied stimuli of temperature and pressure was presented for a deeper understanding of the atomistic origin of the ZnO Raman shift. Theoretical reproduction based on the BOLS correlation theory [Sun, C. Q. Prog. Solid State Chem. 2007, 35, 1] and the local bond average (LBA) approach [Sun, C. Q. Prog. Mater. Sci. 2009, 54, 179] of the measurements revealed that the thermally softened ZnO Raman modes arise from bond expansion and bond weakening due to vibration and that the pressure-stiffened Raman modes result from bond compression and bond strengthening due to mechanical work hardening. The developed approach could be useful in generalizing the lattice dynamics directly to the process of vibration and relaxation of a representative bond of the specimen under external stimuli.