Effectiveness and safety of REBACIN as a non-invasive intervention for persistent high-risk human papillomavirus infection: A real-world prospective multicenter cohort study.

BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.

The Relationship between Iron and LRRK2 in a 6-OHDA-Induced Parkinson's Disease Model.

The pathogenesis of Parkinson's disease (PD) is very complex and still needs further exploration. Leucine-rich repeat kinase 2 (LRRK2) is associated with familial PD in mutant forms and sporadic PD in the wild-type form. Abnormal iron accumulation is found in the substantia nigra of PD patients, but its exact effects are not very clear. Here, we show that iron dextran exacerbates the neurological deficit and loss of dopaminergic neurons in 6-OHDA lesioned rats. 6-OHDA and ferric ammonium citrate (FAC) significantly increase the activity of LRRK2 as reflected by the phosphorylation of LRRK2, at S935 and S1292 sites. 6-OHDA-induced LRRK2 phosphorylation is attenuated by the iron chelator deferoxamine, especially at the S1292 site. 6-OHDA and FAC markedly induce the expression of pro-apoptotic molecules and the production of ROS by activating LRRK2. Furthermore, G2019S-LRRK2 with high kinase activity showed the strongest absorptive capacity for ferrous iron and the highest intracellular iron content among WT-LRRK2, G2019S-LRRK2, and kinase-inactive D2017A-LRRK2 groups. Taken together, our results demonstrate that iron promotes the activation of LRRK2, and active LRRK2 accelerates ferrous iron uptake, suggesting that there exists an interplay between iron and LRRK2 in dopaminergic neurons, providing a new perspective to uncover the underlying mechanisms of PD occurrence.

Bacterial vaginosis, vulvovaginal candidiasis, and trichomonal vaginitis in reproductive-age women in Yunnan, China: a descriptive study.

This study aimed to determine the prevalence of and risk factors associated with BV(bacterial vaginosis, BV), VVC (vulvovaginal candidiasis, VVC) and TV (trichomonal vaginitis, TV) among non-pregnant women. Among 770 women included in analyses, surveyed using a questionnaire and subsequently diagnosed with BV, VVC and TV via Gram staining and vaginal swab microscopy. Vaginal infections were prevalent in 31.30%, with BV being the most prevalent (21.35%). Single-variable analysis revealed that an age of 20-29 years (odds ratio [OR] = 2.31, 95% CI: 1.24-4.29; p = .007) and lack of education (OR = 0.50, 95% CI: 0.28-0.89; p = .018) were significantly associated with BV. However, an age of 30-39 years was significantly associated with VVC (OR = 2.12, 95% CI: 1.03-4.38; p = .038). Multivariable analysis confirmed that miscarriage was an independent predictor of BV and VVC. Miscarriage was significantly associated with the incidence of BV and VVC (OR = 1.680, 95% CI: 1.146-2.462; p = .011 and OR = 2.04, 95% CI: 1.30-3.20; p = .002, respectively). In conclusion, BV appears to be the predominant cause of vaginitis, risk factors for vaginitis include age and level of education and miscarriage.IMPACT STATEMENTWhat is already known on this subject? Inflammation of the vagina, or vaginitis, is caused by various infectious and non-infectious factors. The most common causes of infectious vaginitis are BV, VVC and TV. Kunming located at the southwestern border of China, However, there is still no systematic research investigating the status of vaginitis infection in Yunnan Province. Therefore, the present study aimed to determine the prevalence of these vaginal infections; BV, VVC, and TV, among women of childbearing age, and to assess the prevalence of vaginal infections and the associated risk factors.What do the results of this study add? In our study we found that vaginal infections were prevalent in 31.30% of reproductive-age women, with BV being the most prevalent (21.35%). We believe that our study makes a significant contribution to the literature because we report that BV appears to be the predominant cause of vaginitis, followed by VVC and TV. Risk factors for vaginitis include age, miscarriage and level of education.What are the implications of these findings for clinical practice and/or further research? This study aimed to determine the prevalence of these vaginal infections, BV, VVC and TV, and to assess the prevalence of vaginal infections and the associated risk factors. Health education interventions are recommended to raise women's awareness of vaginitis and its prevention.

The involvement of nuclear factor-κB in astroprotection against ischemia-reperfusion injury by ischemia-preconditioned neurons.

Ischemic preconditioned (IP) neurons protect astrocytes against ischemia/reperfusion (I/R)-induced injury by inhibiting oxidative stress. However, the relevant mechanisms are unknown. Based on the role of nuclear factor-κB (NF-κB) in cell survival and adaption to oxidative stress, we hypothesized that NF-κB might be associated with astroprotection induced by IP neurons via upregulation of antioxidant enzymes. Here, we investigated the effects of IP neurons on NF-κB activation, cell viability, reactive oxygen species (ROS), expression of antioxidant enzymes, erythropoietin (EPO), and tumor necrosis factor α (TNF-α), in the presence or absence of BAY11-7082 (an NF-κB inhibitor), anti-EPO, and anti-TNF-α antibodies, in astrocytes treated with or without I/R. We found that IP neurons could keep NF-κB activation at a relatively higher but beneficial level, and in turn, upregulated the activity of antioxidant enzymes and hence enhanced cell viability and reduced ROS in I/R treated astrocytes. The results collectively indicated that IP neurons are able to significantly inhibit the I/R-induced NF-κB overactivation, probably via EPO and TNF-α, being essential for IP neuron-induced astroprotection under the conditions of I/R. We concluded that NF-κB-mediated antioxidative stress is one of the mechanisms by which IP neurons protect astrocytes against I/R injury.

Cryptochrome 2 from Lilium × formolongi Regulates Photoperiodic Flowering in Transgenic Arabidopsis thaliana.

The photoperiodic flowering pathway is essential for plant reproduction. As blue and ultraviolet-A light receptors, cryptochromes play an important role in the photoperiodic regulation of flowering. Lilium × formolongi is an important cut flower that flowers within a year after seed propagation. Floral induction is highly sensitive to photoperiod. In this study, we isolated the CRYPTOCHROME2 gene (LfCRY2) from L. × formolongi. The predicted LfCRY2 protein was highly homologous to other CRY2 proteins. The transcription of LfCRY2 was induced by blue light. LfCRY2 exhibits its highest diurnal expression during the floral induction stage under both long-day and short-day photoperiods. Overexpression of LfCRY2 in Arabidopsis thaliana promoted flowering under long days but not short days, and inhibited hypocotyl elongation under blue light. Furthermore, LfCRY2 was located in the nucleus and could interact with L. × formolongi CONSTANS-like 9 (LfCOL9) and A. thaliana CRY-interacting basic-helix-loop-helix 1 (AtCIB1) in both yeast and onion cells, which supports the hypothesis that LfCRY2 hastens the floral transition via the CIB1-CO pathway in a manner similar to AtCRY2. These results provide evidence that LfCRY2 plays a vital role in promoting flowering under long days in L. × formolongi.

The Runx1/Notch1 Signaling Pathway Participates in M1/M2 Microglia Polarization in a Mouse Model of Temporal Lobe Epilepsy and in BV-2 Cells.

Microglial activation and phenotypic shift play vital roles in many neurological diseases. Runt-related transcription factor-1 (Runx1), which is localized on microglia, inhibits amoeboid microglial proliferation. Preliminary data have indicated that the interaction of Runx1 with the Notch1 pathway affects the hemogenic endothelial cell shift. However, little is known about the effect of Runx1 and the Notch1 signaling pathway on the phenotypic shift of microglia during neuroinflammation, especially in temporal lobe epilepsy (TLE). A mouse model of TLE induced by pilocarpine and the murine microglia cell line BV-2 were used in this study. The proportion of microglia was analyzed using flow cytometry. Western blot (WB) analysis and quantitative real-time polymerase chain reaction were used to analyze protein and gene transcript levels, respectively. Immunohistochemistry was used to show the distribution of Runx1. In the present study, we first found that in a male mouse model of TLE induced by pilocarpine, flow cytometry revealed a time-dependent M2-to-M1 microglial transition after status epilepticus. The dynamic expression patterns of Runx1 and the downstream Notch1/Jagged1/Hes5 signaling pathway molecules in the epileptic hippocampus were determined. Next, Runx1 knockdown by small interfering RNA in BV-2 cells strongly promoted an M2-to-M1 microglial phenotype shift and inhibited Notch1/Jagged1/Hes5 pathway expression. In conclusion, Runx1 may play a critical role in the M2-to-M1 microglial phenotype shift via the Notch1 signaling pathway during epileptogenesis in a TLE mouse model and in BV-2 cells.

Cystathionine ß-synthase is required for body iron homeostasis.

Cystathionine ß-synthase (CBS) catalyzes the transsulfuration pathway and contributes, among other functions, to the generation of hydrogen sulfide. In view of the exceptionally high expression of CBS in the liver and the common interleukin-6 pathway used in the regulatory systems of hydrogen sulfide and hepcidin, we speculate that CBS is involved in body iron homeostasis. We found that CBS knockout (CBS-/- ) mice exhibited anemia and a significant increase in iron content in the serum, liver, spleen, and heart, along with severe damage to the liver, displaying a hemochromatosis-like phenotype. A high level of hepatic and serum hepcidin was also found. A major cause of the systemic iron overload is the reduced iron usage due to suppressed erythropoiesis, which is consistent with an increase in interleukin-6 and reduced expression of erythropoietin. Importantly, in the liver, absence of CBS caused both a reduction in the transcriptional factor nuclear factor erythroid 2-related factor-2 and an up-regulation of hepcidin that led to a decrease in the iron export protein ferroportin 1. The resulting suppression of iron export exacerbates iron retention, causing damage to hepatocytes. Finally, administration of CBS-overexpressing adenovirus into CBS mutant mice could partially reverse the iron-related phenotype. CONCLUSION: Our findings point to a critical role of CBS in iron homeostasis of the body, and the liver in particular; it is likely that a hemochromatosis-like phenotype in patients can be induced by aberration not only in the expression of key molecules in the hepcidin pathway but also of those related to CBS. (Hepatology 2018;67:21-35).

Significance of histological crescent formation in patients with IgA vasculitis (Henoch-Schönlein purpura)-related nephritis: a cohort in the adult Chinese population.

BACKGROUND: IgA vasculitis (IgAV, formerly Henoch-Schönlein purpura) is a type of systemic vasculitis. This study aimed to explore the clinicopathological features, treatment and renal outcomes of adult IgAV-related nephritis (Henoch-Schönlein purpura nephritis) patients with different degrees of crescent formation. METHODS: Adult patients with biopsy-proven IgAV-related nephritis in Nanjing Jinling Hospital were enrolled and divided into three groups as follows: control (no crescents, n = 257), group 1 (crescents < 25%, n = 381), and group 2 (crescents ≥25%, n = 60). The clinicopathological features, treatment and renal outcomes were compared among the three groups. RESULTS: There were no significant differences in gender and age at biopsy among the three groups. Groups with more crescents had shorter renal durations and higher prevalence of macroscopic hematuria, proteinuria and nephrotic syndrome than the control group. The presence of renal insufficiency at biopsy was similar, whereas laboratory findings indicated that patients with ≥25% crescents had higher levels of serum creatinine and blood urea nitrogen than the control and group 1. Histologically, the incidence of glomeruli-Bowman's capsule adhesion and capillary necrosis were proportional to the degree of crescent formation. Patients with more crescents received more positive immunosuppressive therapies. During follow-up, the levels of proteinuria and hematuria were in remission after treatment, and patients without crescents had lower levels of proteinuria. At the last follow-up, the renal function had deteriorated in the control and group 1, whereas the levels of serum creatinine at biopsy and last follow-up were similar in group 2. There was a significant difference in renal survival from end-stage renal disease (ESRD) or 50% decline in renal function among the three groups (log-rank, P = 0.030). However, no association between crescent formation and renal outcomes was found after adjusting potential confounders. CONCLUSIONS: Adult IgAV-related nephritis patients with more crescents had more-severe renal manifestations and worse treatment responses, whereas the proportions of crescents were not associated with higher risks for ESRD or 50% decline in renal function. A more suitable pathological classification standard is needed to predict renal prognosis.

Type D personality is associated with delaying patients to medical assessment and poor quality of life among rectal cancer survivors.

OBJECTIVE: The aim of this research was to explore quality of life (QoL), mental health status, type D personality, symptom duration, and emergency admissions of Chinese rectal cancer patients as well as the relationship between these factors. METHODS: Type D personality was measured with the 14-item Type D Personality Scale (DS14). Mental health status was measured with the Hospital Anxiety and Depression Scale (HADS). The QoL outcomes were assessed longitudinally using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 questionnaires at the baseline and 6 months after diagnosis. RESULTS: Of the 852 survivors who responded (94 %), 187 (22 %) had a type D personality. The proportion of patients with duration of symptoms >1 month and being diagnosed after emergency admissions in type D group is significantly higher than that in non-type D group. At both of the time points, type D patients reported statistically significant lower scores on most of the functional scales, global health status/QoL scales, and worse symptom scores compared to patients without a type D personality. At the 6-month time point, a higher percentage of patients in the type D group demonstrated QoL deterioration. Clinically elevated levels of anxiety and depression were more prevalent in type D than in non-type D survivors. CONCLUSIONS: Type D personality was associated with poor QoL and mental health status among survivors of rectal cancer, even after adjustment for confounding background variables. Type D personality might be a general vulnerability factor to screen for subgroups at risk for longer symptom duration and emergency admissions in clinical practice.

Significance of mast cell renal infiltration in patients with anti-GBM nephritis.

To investigate the role of mast cells (MCs) renal infiltration in the progression of human anti-GBM nephritis, 38 patients diagnosed with anti-GBM nephritis were enrolled. Renal biopsies were performed. Immunohistochemistry was conducted to detect MCs in renal tissues. Patients were divided into group 1 (MCs <50 mm(-2), n = 18) and group 2 (MCs ≥50 mm(-2), n = 20) according to the infiltrating renal MC count. The clinical-pathological indices were compared. And, correlation between MCs and the clinical-pathological indices was analyzed. Patients of group 2 had more severe renal dysfunctions, expressed as higher levels of serum creatinine (SCr 8.95 ± 3.66 vs. 4.75 ± 2.73 mg/dL, p < 0.001), urine retinol-binding protein (RBP 29.8 ± 13.9 vs. 15.7 ± 11.5 mg/dL, p = 0.005), and lower urinary osmotic pressure. Pathologically, patients of group 2 had a higher percentage of fibrous/fibrocellular crescents (66.7 ± 21.9 vs. 47.0 ± 33.6%, p = 0.037) but a lower percentage of cellular crescents. More CD8 (268 mm(-2) vs. 180 mm(-2), p = 0.045) and CD68 (268 mm(-2) vs. 180 mm(-2), p = 0.045) positive cells infiltrating the interstitium were observed in group 2. Furthermore, renal MCs correlated significantly with the total number of crescents and the tubular interstitial CD8 and CD68 positive cells. And, the number of MCs was associated with the histological types. The renal function was significantly different between the two groups at presentation. However, at 3 and 6 month follow-up, the patient outcome was associated with the histological types. Our study showed that MC infiltrations were associated with chronic lesions in anti-GBM nephritis and may be involved in the loss of renal function with pathological changes.

The effect and mechanism of low-molecular-weight heparin on the decidualization of stromal cells in early pregnancy.

OBJECTIVE: This study aimed to analyze the effect of low-molecular-weight heparin (LMWH) on the decidualization of stromal cells in early pregnancy and explore the effect of LMWH on pregnancy outcomes. METHODS: Recurrent spontaneous abortion (RSA) mouse model (CBA/J × DBA/2) and normal pregnant mouse model (CBA/J × BALB/c) were established. The female mice were checked for a mucus plug twice daily to identify a potential pregnancy. When a mucus plug was found, conception was considered to have occurred 12 h previously. The pregnant mice were divided randomly into a normal pregnancy control group, an RSA model group, and an RSA + LMWH experimental group (n = 10 mice in each group). Halfway through the 12th day of pregnancy, the embryonic loss of the mice was observed; a real-time quantitative polymerase chain reaction was used to detect the messenger ribonucleic acid (mRNA) expressions of prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1) in the decidua of the mice. Additionally, the decidual tissues of patients with RSA and those of normal women in early pregnancy who required artificial abortion were collected and divided into an RSA group and a control group. Decidual stromal cells were isolated and cultured to compare cell proliferation between the two groups, and cellular migration and invasion were detected by membrane stromal cells. Western blotting was used to detect the protein expressions of proliferating cell nuclear antigen (PCNA), cyclin D1, matrix metalloproteinase- (MMP) 2, and MMP-7 in stromal cells treated with LMWH. RESULTS: Compared with the RSA group, LMWH significantly reduced the pregnancy loss rate in the RSA mice (p < 0.05). Compared with the RSA group, the LMWH + RSA group had significantly higher expression levels of PRL and IGFBP1 mRNA (p < 0.01). LMWH promoted the proliferation, migration, and invasion of human decidual stromal cells; compared with the control group, the expression levels of MMP-2, MMP-7, cyclin D1, and PCNA proteins in the decidual stromal cells of the LMWH group increased (p < 0.05). CONCLUSIONS: The use of LMWH can improve pregnancy outcomes by enhancing the proliferation and migration of stromal cells in early pregnancy and the decidualization of stromal cells.

Glutenin-chitosan 3D porous scaffolds with tunable stiffness and systematized microstructure for cultured meat model.

A glutenin (G)-chitosan (CS) complex (G-CS) was cross-linked by water annealing with aim to prepare structured 3D porous cultured meat scaffolds (CMS) here. The CMS has pore diameters ranging from 18 to 67 µm and compressive moduli from 16.09 to 60.35 kPa, along with the mixing ratio of G/CS. SEM showed the porous organized structure of CMS. FTIR and CD showed the increscent content of α-helix and ß-sheet of G and strengthened hydrogen-bondings among G-CS molecules, which strengthened the stiffness of G-CS. Raman spectra exhibited an increase of G concentration resulted in higher crosslinking of disulfide-bonds in G-CS, which aggrandized the bridging effect of G-CS and maintained its three-dimensional network. Cell viability assay and immuno-fluorescence staining showed that G-CS effectively facilitated the growth and myogenic differentiation of porcine skeletal muscle satellite cells (PSCs). CLSM displayed that cells first occupied the angular space of hexagon and then ring-growth circle of PSCs were orderly formed on G-CS. The texture and color of CMS which loaded proliferated PSCs were fresh-meat like. These results showed that physical cross-linked G-CS scaffolds are the biocompatible and stable adaptable extracellular matrix with appropriate architectural cues and natural micro-environment for structured CM models.

Anticonvulsant activity of acute and chronic treatment with a-asarone from Acorus gramineus in seizure models.

For centuries, extracts of Acorus gramineus have been used extensively in traditional Chinese medicine for the treatment, management, and/or control of human ailments, including central nervous system disorders such as convulsions and epilepsy. In the present study, we investigated the anticonvulsant activity of chronic treatment with the plant's major essential oil component (a-asarone, 50-200 mg/kg, per os (p.o.)) against maximal electroshock seizure (MES), pentylenetetrazole (PTZ)-induced seizures in mice, lithium-pilocarpine (LI-PILO)-induced status epilepticus (SE), and spontaneous recurrent seizures (SRSs) in rats and determined whether a single acute administration of a-asarone at various doses could produce anticonvulsant activity. As the standard antiepileptic drugs used, chronically administered a-asarone (50-200 mg/kg, p.o.) significantly delayed (p<0.05) the onset of, and antagonized maximal electroshock seizure and PTZ-induced seizures. Chronically administered a-asarone (50-200 mg/kg) also profoundly antagonized LI-PILO-induced seizures. The SE incidence, SE latency and seizure severity as well as mortality were significantly reduced after treatment with a-asarone at different doses. Higher doses of a-asarone (100-200 mg/kg) significantly reduced spontaneous recurrent seizure incidence, severity, and seizure frequency during treatment in LI-PILO-induced SRSs rats. On the other hand, a single acute administration of a-asarone (50-200 mg/kg) produced weak anticonvulsant activity in MES and PTZ-induced seizures. The results of this laboratory animal study indicate that chronically administered a-asarone possesses anticonvulsant activity in the mammalian experimental model used, and thus suggest that a-asarone may be used as a natural supplementary remedy in the management of convulsions and epilepsy.

[Clinical observation of home noninvasive positive pressure ventilation in hypercapnic patient with stable severe chronic obstructive pulmonary disease].

OBJECTIVE: To evaluate the efficacy and safety of home noninvasive positive pressure ventilation (HNIPPV) in hypercapnic patients with stable severe chronic obstructive pulmonary disease (COPD). METHODS: Forty four patients (30 males and 14 females, mean age 68.5 years (range: 60 - 80)) were recruited from a total of 106 patients with arterial PaCO2 ≥ 55 mm Hg in Second Hospital Affiliated to Harbin Medical University from January 2009 to December 2010. Their clinical data were collected and analyzed. The patients in the HNIPPV group (n = 20) accepted tiotropium bromide, doxofylline tablets and HNIPPV treatment while those in the control group (n = 24) tiotropium bromide, doxofylline tablets and a low-flow inhalation of oxygen. The entire observation period was 6 months. The parameters before and after 6-month follow-up were compared, including lung function test, 6-min walking distance (6MWD), arterial blood gases (PaO2 and PaCO2), dyspnea grade, scores of emotional disorders and mean pulmonary artery pressure (mPAP). RESULTS: No significant difference existed in the baseline data between the HNIPPV and control groups. The forced expiratory volume in one second (FEV(1)), forced vital capacity (FVC), inspiratory capacity (IC), 6MWD, PaO2, PaCO2, dyspnea grade, hospitalization rate, anxiety scores, depression scores and mPAP showed no significant difference between the HNIPPV and control groups before treatment. However, at Month 6, the differences of IC, 6MWD, PaO2, PaCO2, dyspnea grade, anxiety scores, depression scores and mPAP in HNIPPV group ((1.80 ± 0.14) L, (266 ± 24) m, (62.6 ± 4.6) mm Hg, (46.8 ± 2.2) mm Hg, (2.2 ± 0.5), (6.5 ± 2.4), (6.0 ± 1.6), (33.8 ± 2.4) mm Hg) were statistically significant compared with the control group ((1.62 ± 0.14) L, (194 ± 23) m, (56.2 ± 3.8) mm Hg, (55.6 ± 3.0) mm Hg, (3.2 ± 0.6), (10.6 ± 2.8), (10.2 ± 2.4), (36.6 ± 2.4) mm Hg) (P values: 0.031, 0.018, 0.025, 0.026, 0.001, 0.013, 0.002, 0.014 respectively). FEV(1) and FVC in the HNIPPV group improved slightly but with no statistically significant difference (all P > 0.05). Two patients in the control group were taken to hospital because of acute exacerbation. And hospitalization rates increased in the control group. But no statistically significant difference existed between the HNIPPV and control groups (P > 0.05). The tolerance and compliance of HNIPPV in the HNIPPV group were better and the patients in the HNIPPV group had no pulmonary barotraumas. CONCLUSION: HNIPPV plus tiotropium bromide and doxofylline tablets is both effective and safe in the treatment of hypercapnic patient with stable severe COPD.

[Clinical curative effects of preoperative neoadjuvant chemotherapy on cervical cancer: analysis of 62 patients].

OBJECTIVE: To explore the clinical curative effects of preoperative neoadjuvant chemotherapy (NACT) on locally advanced cervical cancer. METHODS: A total of 62 patients of stage Ib2-IIb cervical cancer received neoadjuvant chemotherapy of paclitaxel plus cisplatin for 2 - 3 courses. The clinical curative effects were evaluated according to the changes of lesion size, intraoperative conditions and postoperative pathological reactions. RESULTS: The overall response rate was 90.32% (56/62) and the complete response rate 30.65% (19/62). The tumor volumes decreased after NACT. The differences were significant (P < 0.05). After NACT, 56 patients undergoing radical hysterectomy recovered smoothly. The surgical resection rate was 90.32%. Chemotherapeutic reactions of cancerous tissue and a large number of infiltrated lymphocytes were seen in 50 cases. Lymph nodes were positive in 3 cases. There were parametrial invasion (n = 2) and vascular tumor emboli (n = 2). CONCLUSION: Preoperative neoadjuvant chemotherapy is efficacious in cervical cancer. The parametrium becomes softer and the tumor staging decreases.

[Expression of HSP27 in CA1 area of hippocampus in temporal lobe epilepsy model].

OBJECTIVE: To explore the expression of heat shock protein 27 (HSP27) in the CA1 area of hippocampus in temporal lobe epilepsy (TLE) so as to elucidate the relationship between HSP27 and epileptogenesis of TLE. METHODS: The model of TLE was induced by lithium-pilocarpine in the experiment group. And the rats were further divided into the STLE and non-STLE groups based upon the absence or presence of recurrent spontaneous seizure in the next 30 days. Total protein fractions from CA1 area of hippocampus were successively obtained through tissue homogenates abstraction. The HSP27 expression in the CA1 area of hippocamp from three groups was semi-quantitatively analyzed by Western blot. And the expression of HSP27 in CA1 area was detected by pre-embedding immunogold electron microscopy. RESULTS: Expression of HSP27 in the hippocampus CA1 area as detected by Western blot was in accord with that by immunogold electron microscopy. Relative optical density values were 0.912 ± 0.011, 0.431 ± 0.011 and 0.428 ± 0.010 respectively. And gold particles were 50.0 ± 4.2, 23.0 ± 2.8 and 20.0 ± 2.3 respectively. The expression of HSP27 was the highest in the hippocampus CA1 area of the STLE group. There was statistical significance as compared with the non-STLE and normal groups (P = 0.0001). The non-STLE group was higher than the normal group. But there was no significant difference as compared with the normal group (P = 0.63). CONCLUSIONS: HSP27 in the hippocampus CA1 area may participate in the epileptogenesis of TLE.

[The effect of marrow mesenchymal stem cell transplantation on pulmonary fibrosis in rats].

OBJECTIVE: To study the possible mechanisms of marrow mesenchymal stem cells (MSC) in therapy of bleomycin (BLM)-induced pulmonary fibrosis in rats. METHODS: Fifty-four female Wistar rats were randomly divided into a control group, a BLM group and a MSC group. The control group received intratracheal normal saline, the BLM group received intratracheal instillation of bleomycin, and the MSC group was injected with male rat MSC solution of 0.5 ml (2.5×10(6) cells) via the tail vein after intratracheal instillation of bleomycin. Six rats from each group were killed on day 7, 14 and 28 of the experiments. BrdU labeling rate was measured before MSC transplantation. Lung tissue specimens were obtained for pathological examination, hydroxyproline content measurement, and detection of the expression of type II alveolar cell (ATII) specific marker-pulmonary surfactant protein-C (SP-C) in BrdU labeled MSC using dual immunofluorescence method. RT-PCR method was used to detect SP-C mRNA expression in the lung tissue and the bone marrow at different stages. The bone marrow mobilization involved in repair of type II alveolar cells after lung injury was observed. RESULTS: The final concentration of BrdU labeled MSC at 48 h was 10 µmol/L, while the labeling efficiency was>98%, and the passage cells could be continuously labeled. In the MSC group, BrdU labeled MSCs with expression of SP-C were observed in all frozen sections of lung tissue at day 7, 14, and 28. By day 28, the lung fibrosis scores of the MSC group and the BLM group were (2.17 ± 0.26) and (2.83 ± 0.24), respectively, the lung tissue hydroxyproline contents were (138 ± 21) mg/g and (184 ± 19) mg/g, respectively, and the lung tissue SP-C mRNA expressions were (0.98 ± 0.15) and (0.59 ± 0.14), respectively. For both groups the SP-C mRNA expressions in the bone marrow at different stages were significantly increased as compared to the control group. CONCLUSIONS: Marrow mesenchymal stem cells could be transplanted into lung tissues of rats, and transformed into type II alveolar cells and was shown to prevent the development of pulmonary fibrosis. The damage-induced enhancement of host bone marrow mobilization was also involved in the repair process.

Advances in the study of axon-associated vesicles.

The central nervous system is the most important and difficult to study system in the human body and is known for its complex functions, components, and mechanisms. Neurons are the basic cellular units realizing neural functions. In neurons, vesicles are one of the critical pathways for intracellular material transport, linking information exchanges inside and outside cells. The axon is a vital part of neuron since electrical and molecular signals must be conducted through axons. Here, we describe and explore the formation, trafficking, and sorting of cellular vesicles within axons, as well as related-diseases and practical implications. Furthermore, with deepening of understanding and the development of new approaches, accumulating evidence proves that besides signal transmission between synapses, the material exchange and vesicular transmission between axons and extracellular environment are involved in physiological processes, and consequently to neural pathology. Recent studies have also paid attention to axonal vesicles and their physiological roles and pathological effects on axons themselves. Therefore, this review mainly focuses on these two key nodes to explain the role of intracellular vesicles and extracellular vesicles migrated from cells on axons and neurons, providing innovative strategy for future researches.

Molecular cloning of cryptochrome 1 from Lilium×formolongi and the characterization of its photoperiodic flowering function in Arabidopsis.

Lilium × formolongi is an important cut flower species that is able to flower within a year following seed propagation, with flower induction that is very sensitive to the photoperiod. Cryptochromes are blue/UV-A light receptors that regulate many important plant growth and development processes, including photoperiodic flowering. In this study, we isolated the cryptochrome 1 (CRY1) gene from L. × formolongi and analyzed its function in transgenic Arabidopsis. The predicted LfCRY1 protein was strongly homologous to other CRY1 proteins. The transcription of LfCRY1 was induced by blue light, with LfCRY1 exhibiting its highest expression and diurnal expression patterns during the flowering-induction stage under both long-day (LD) and short-day (SD) photoperiods. Overexpression of LfCRY1 in Arabidopsis promoted flowering under LDs but not SDs and inhibited hypocotyl elongation under blue light. The LfCRY1 protein was located in both the nucleus and cytoplasm. LfCRY1 interacted with the important flowering activator LfCOL9 in both yeast and onion cells. These results provide functional evidence for the role of LfCRY1 in controlling photoperiodic flowering under LDs and indicate that LfCRY1 may be a counterpart of AtCRY1. Understanding the role of LfCRY1 in photoperiodic flowering is beneficial for the molecular breeding of lilies with shorter vegetative stages.

Genital Microbiota of Women From Six Ethnic Groups With and Without Human Papillomavirus Infection in Shangri-La, China.

Background: A diversity of microorganisms is associated with human health and exists in a state of dynamic equilibrium. This diversity has direct implications for the assessment of susceptibility to infectious diseases, especially human papillomavirus (HPV) infection. Methods: Here, we investigated the relationships between HPV infection and vaginal, cervical, and gut microbiota composition and assessed the levels of genital immune mediators. We selected a multiethnic area in Yunnan Province, China, to collect samples from healthy women of childbearing age. A total of 82 healthy women of childbearing age were included in this study. Vaginal, cervical, and rectal swabs were collected to analyze the microbial community, and cytokines were analyzed in some samples. Findings: Different proportions and types of HPV infection were detected in cervical (44%), vaginal (18%), and rectal (18%) swabs. HPV detected in cervical swabs was generally a high-risk type, while low-risk HPV types were primarily detected in vaginal and rectal swabs. There were some differences in this proportion as well as in the microbial community composition among different ethnic groups. Rectal samples exhibited the highest diversity index, while vaginal samples displayed the lowest diversity index. Lactobacillus dominated most of the vaginal samples, was decreased in HPV-positive samples, and differed among different ethnic groups. However, the sequence proportion of Lactobacillus in the cervix exhibited the opposite trend in those affected by HPV infection. The dynamic balance between the potential pathogens Gardnerella and Lactobacillus determines the health of the female genital system. Interpretation: This study constitutes the first step toward personalized medicine for women's reproductive health, wherein differences between the genital microbiomes of individuals would be considered in risk assessment and for subsequent disease diagnosis and treatment.