ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.

Pudilan Xiaoyan Oral Liquid has effects in clearing away heat and detoxifying,and is used to treat pharynx and throat swelling caused by the syndrome of excessive heat and toxin accumulation. Its efficacy is to relieve swelling and pain( redness,swelling and hot pain). It is included in the Chinese Pharmacopoeia of 2015 Edition,and has been listed in provincial health insurance directories of Shaanxi,Jiangsu,Liaoning,Hunan,Tianjin,Xinjiang and Hebei. It has been recommended by health departments of Beijing,Chongqing and other provinces as a preferred drug for the prevention and treatment of H1 N1 and HFMD,and listed in the diagnosis and Treatment Guide of HFMD by the Ministry of Health,the Clinical Application Guide of Chinese Patent Medicine edited by the Lung Department Disease Branch of China Association of Chinese Medicine,and the Clinical Practice Guide of Single Administration/Combined Administration of Antibiotics in Treatment of Common Infectious Diseases by China Association of Chinese Medicine. To further improve the clinician's understanding of drugs and better guide the rational clinical application,we invited front-line clinical experts from respiratory department,infectious department and dermatology of traditional Chinese and Western medicine to develop and compile the expert consensus. The consensus fully considered the clinical evidence and the expert clinical experience to give recommendations for clinical problems with evidence support and consensus suggestions for clinical problems without evidence support by the nominal group method.This consensus is based on clinical research evidence and expert experience in a simple and clear format,which provides a preliminary reference for the clinical use of the drug.
China ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs

Toxoplasma gondii can infect all the vertebrates including human, and leads to serious toxoplasmosis and considerable veterinary problems. T. gondii heat shock protein 60 (HSP60) is associated with the activation of antigen presenting cells by inducing initial immune responses and releasing inflammatory cytokines. It might be a potential DNA vaccine candidate for this parasite. A pVAX-HSP60 DNA vaccine was constructed and immune responses was evaluated in Kunming mice in this study. Our data indicated that the innate and adaptive immune responses was elicited by successive immunizations with pVAX-HSP60 DNA, showing apparent increases of CD3e+CD4+ and CD3e+CD8a+ T cells in spleen tissues of the HSP60 DNA-immunized mice (24.70±1.23% and 10.90±0.89%, P < 0.05) and higher levels of specific antibodies in sera. Furthermore, the survival period of the immunized mice (10.53±4.78 day) were significantly prolonged during the acute T. gondii infection. Decrease of brain cysts was significant in the experimental group during the chronic infection (P < 0.01). Taken together, TgHSP60 DNA can be as a vaccine candidate to prevent the acute and chronic T. gondii infections.
Animals ; Antibodies ; Antigen-Presenting Cells ; Brain ; Chaperonin 60 ; Cytokines ; DNA ; Humans ; Immunization ; Mice ; Parasites ; Spleen ; T-Lymphocytes ; Toxoplasma ; Toxoplasmosis ; Vertebrates

BACKGROUNDGlobally, the proportion of child deaths that occur in the neonatal period remains a high level of 37-41%. Differences of cause in neonate death exist in different regions as well as in different economic development countries. The specific aim of this study was to investigate the causes, characteristics, and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit (NICU) of China.

METHODSAll the dead neonates admitted to 26 NICUs were included between January l, 2011, and December 31, 2011. All the data were collected retrospectively from clinical records by a designed questionnaire. Data collected from each NICU were delivered to the leading institution where the results were analyzed.

RESULTSA total of 744 newborns died during the 1-year survey, accounting for 1.2% of all the neonates admitted to 26 NICUs and 37.6% of all the deaths in children under 5 years of age in these hospitals. Preterm neonate death accounted for 59.3% of all the death. The leading causes of death in preterm and term infants were pulmonary disease and infection, respectively. In early neonate period, pulmonary diseases (56.5%) occupied the largest proportion of preterm deaths while infection (27%) and neurologic diseases (22%) were the two main causes of term deaths. In late neonate period, infection was the leading cause of both preterm and term neonate deaths. About two-thirds of neonate death occurred after medical care withdrawal. Of the cases who might survive if receiving continuing treatment, parents' concern about the long-term outcomes was the main reason of medical care withdrawal.

CONCLUSIONSNeonate death still accounts for a high proportion of all the deaths in children under 5 years of age. Our study showed the majority of neonate death occurred in preterm infants. Cause of death varied with the age of death and gestational age. Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical decision.

Cause of Death ; China ; Female ; Hospital Mortality ; Humans ; Infant ; Infant Mortality ; Infant, Newborn ; Infant, Newborn, Diseases ; mortality ; Intensive Care Units, Neonatal ; statistics & numerical data ; Male ; Perinatal Death ; Retrospective Studies

The constituents in 95% ethanol extract of the root of Rosa cymosa Tratt were purified by column chromatography techniques, leading to isolation of eleven triterpenes. Their structures were elucidated by spectroscopic data as pomolic acid (1), fupenzic acid (2), ursolic acid (3), euscaphic acid (4), arjunic acid (5), tomentic acid (6), 3β-E-feruloyl corosolic acid (7), 1β-hydroxyeuscaphic acid (8), myrianthic acid (9), cecropiacic acid (10), and ilexoside B (11). Among them, compounds 3, 6-8, 10 and 11 were obtained from this plant for the first time, and compounds 7 and 10 were obtained from this genus for the first time.
Drugs, Chinese Herbal ; chemistry ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Plant Roots ; chemistry ; Rosa ; chemistry ; Triterpenes ; chemistry

OBJECTIVETo study the effects of high frequency oscillatory ventilation (HFOV) combined with incremental positive end-expiratory pressure (IP) on respiratory and circulatory functions, and lung histopathology of dogs with smoke inhalation injury.

METHODSAfter being treated with conventional mechanical ventilation, 12 dogs were inflicted with severe smoke inhalation injury and divided into group HFOV and group HFOV+IP according to the random number table, with 6 dogs in each group. Then they received corresponding ventilation for 8 hours respectively. Blood gas analysis results (pH value, PaO2 and PaCO2 levels) and hemodynamic parameters [heart rate, mean arterial pressure (MAP), pulmonary arterial pressure (PAP), central venous pressure (CVP), cardiac output (CO)] were recorded before injury, immediately after injury, and at post ventilation hour (PVH) 2, 4, 6, and 8. The dogs of two groups were sacrificed at PVH 8. A healthy dog without any treatment and a dog with smoke inhalation injury but no subsequent treatment were sacrificed in addition. Lung tissues of all dogs were obtained for histopathological observation. Lung injury score examination was conducted in both groups. Data were processed with rank sum test, analysis of variance of repeated measurement, and LSD- t test.

RESULTS(1) The PaO2 levels in both groups were significantly decreased immediately after injury, compared with those before injury (with t values respectively 4.960, 5.310, P values all below 0.01). The PaO2 levels in both groups from PVH 2 to PVH 8 were significantly increased, compared with those observed immediately after injury (with t values from 4.930 to 6.050, P values all below 0.01). At PVH 2, 4, and 8, PaO2 levels in group HFOV+IP were significantly higher than those in group HFOV (with t values from 3.775 to 5.774, P values all below 0.01); no statistically significant differences were observed in pH value and PaCO2 level at each time point between two groups (with t values from 0.002 to 0.997, P values all above 0.05). (2) There were no statistically significant differences in MAP, PAP, and CVP within two groups at each time point (with F values from 1.316 to 4.959, P values all above 0.05). In group HFOV, heart rate from PVH 2 to PVH 8 was significantly lower than that observed immediately after injury (with t values from 3.780 to 8.970, P values all below 0.01). In group HFOV+IP, CO at PVH 4, 6, and 8 was significantly lower than that observed immediately after injury (with t values from 3.990 to 11.200, P values all below 0.01). There were no statistically significant differences in MAP, PAP, and CVP between two groups at the same time point (with t values from 0.089 to 2.123, P values all above 0.05). At PVH 4, 6, and 8, heart rate in group HFOV+IP was higher than that in group HFOV (with t values from 2.931 to 7.229, P < 0.05 or P < 0.01), while CO was lower (with t values from 4.297 to 11.206, P values all below 0.01). (3) Compared with those of the healthy dog, inflammatory cell infiltration and bleeding in the lung were observed in alveolar space in both group HFOV and group HFOV+IP, while the degree was less serious than that of the dog with smoke inhalation injury only. Compared with those of group HFOV, inflammatory cell infiltration in group HFOV+IP was less significant, the alveolar structure was relatively intact, and no thickening of alveolar walls was observed. The lung injury score in group HFOV [(3.27 ± 0.24) points] was higher than that of group HFOV+IP [(2.79 ± 0.31) points, t = 27, P < 0.05].

CONCLUSIONSHFOV combined with IP can improve gas exchange and alleviate pulmonary injury without any adverse effect on blood gas analysis or hemodynamic parameters. Therefore, it may be considered as an appropriate mode of ventilation for the treatment of smoke inhalation injury.

Animals ; Blood Gas Analysis ; Burns, Inhalation ; physiopathology ; therapy ; Disease Models, Animal ; Dogs ; Hemodynamics ; High-Frequency Ventilation ; Male ; Positive-Pressure Respiration ; Smoke ; adverse effects

OBJECTIVEImprovement in lung function was reported after acupuncture treatment of chronic obstructive pulmonary disease (COPD), but little is known about the underlying mechanisms. Because an immune response imbalance could be seen in COPD, we hypothesize that electroacupuncture (EA) may play a role in regulating inflammatory cytokines and contribute to lung protection in a rat model of smoke-induced COPD.

METHODSA COPD model using male Sprague-Dawley rats exposed to cigarette smoke was established. The rats were randomly divided into four groups (control, sham, COPD, and COPD plus EA), and COPD model was evaluated by measuring pulmonary pathological changes and lung function. EA was applied to the acupuncture point Zusanli (ST36) for 30 min/d for 14 d in sham and COPD rats. Bronchoalveolar lavage fluid (BALF) was used to measure levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and malonaldehyde (MDA).

RESULTSCompared with the control rats, COPD rats had significant changes in lung resistance (RL) and lung compliance (CL) (both P<0.01), bronchi and bronchiole airway obstruction (P<0.01), and levels of MDA, TNF-α, and IL-1β (P<0.01). There were no significant differences between the control and the sham groups. Compared with the COPD rats, the COPD plus EA rats had decreased RL and increased CL (both P<0.05), and reduced bronchi and bronchiole airway obstruction (P<0.05, P<0.01, respectively), while levels of TNF-α, IL-1β, and MDA in BALF were lowered (P<0.05 and P<0.01, respectively). However, TNF-α and IL-1β levels of the EA group rats remained higher than those of the control group (P<0.05).

CONCLUSIONEA at ST36 can reduce lung injury in a COPD rat model, and beneficial effects may be related to down-regulation of inflammatory cytokines. The anti-inflammatory and antioxidant effects may prolong the clinical benefit of EA.

Acupuncture Points ; Animals ; Bronchoalveolar Lavage Fluid ; immunology ; Disease Models, Animal ; Electroacupuncture ; Humans ; Interleukin-1beta ; immunology ; Male ; Pulmonary Disease, Chronic Obstructive ; etiology ; immunology ; therapy ; Rats ; Rats, Sprague-Dawley ; Smoking ; adverse effects ; Tumor Necrosis Factor-alpha ; immunology

This study is to investigate the effect of high altitude hypoxia on the activity and protein expression of CYP2C9 and CYP2C19. Rats from plain (P) and rats with acute middle altitude hypoxia (AMH), chronic middle altitude hypoxia (CMH), acute high altitude hypoxia (AHH) and chronic high altitude hypoxia (CHH) were administered orally phenytoin sodium (PHT) and omeprazole (OMZ) to evaluate the activity of CYP2C9 and CYP2C19, separately. The serum concentrations of PHT and metabolite 4'-hydroxyphenytoin (HPPH) at 12 h after treatment and the serum concentrations of OMZ and metabolite 5-hydroxy omeprazole (5-OHOMZ) at 3 h after treatment were determined by RP-HPLC. The activity of CYP2C9 and CYP2C19 was evaluated by the ratio of HPPH to PHT and the ratio of 5-OHOMZ to OMZ, respectively. The protein expressions of CYP2C9 and CYP2C19 were determined by ELISA method. The activities of CYP2C9 (HPPH/PHT) in P, AMH, CMH, AHH and CHH were 0.67 +/- 0.31, 0.75 +/- 0.29, 0.76 +/- 0.23, 0.79 +/- 0.31 and 0.75 +/- 0.18, respectively, and the activities of CYP2C19 (5-OHOMZ/OMZ) in P, AMH, CMH, AHH and CHH were 0.17 +/- 0.06, 0.20 +/- 0.10, 0.11 +/- 0.05, 0.37 +/- 0.13 and 0.19 +/- 0.05, respectively. The protein expressions of CYP2C9 in P, AMH, CMH, AHH and CHH were 4.20 +/- 1.27, 3.95 +/- 0.81, 3.93 +/- 1.11, 4.32 +/- 1.03 and 4.12 +/- 0.86 ng x g(-1), respectively, and the protein expressions of CYP2C19 in P, AMH, CMH, AHH and CHH were 3.91 +/- 1.82, 3.63 +/- 2.07, 2.55 +/- 0.85, 4.78 +/- 2.37 and 3.51 +/- 1.03 ng x g(-1), respectively. The activities and protein expressions of CYP2C9 in AMH, CMH, AHH and CHH were not significantly different with those of P. The protein expressions of CYP2C19 in AMH, CMH, AHH and CHH were not significantly different with those of P, but the activity of CYP2C19 in AHH was significantly higher than that of P. This study found significant changes in the activity of CYP2C19 under the special environment of acute high altitude hypoxia.
2-Pyridinylmethylsulfinylbenzimidazoles ; blood ; Administration, Oral ; Altitude ; Animals ; Cytochrome P-450 Enzyme System ; metabolism ; Enzyme Activation ; Female ; Hypoxia ; metabolism ; Male ; Omeprazole ; administration & dosage ; blood ; pharmacokinetics ; Phenytoin ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

To clarify the important functional residues in the active site of N-myristoyltransferase (NMT), a novel antifungal drug target, and to guide the design of specific inhibitors, multiple sequence alignments were performed on the NMT family and thus evolutionary trace was constructed. The important functional residues in myristoyl CoA binding site, catalytic center and inhibitor binding site of NMT family were identified by ET analysis. The trace residues were mapped onto the active site of CaNMT. Trpl26, Asn175 and Thr211 are highly conserved trace residues and do not interact with current NMT inhibitors, which are potential novel drug binding sites for the novel inhibitor design. Pro338, Leu350, Ile352 and Ala353 are class-specific trace residues, which are important for the optimization of current NMT inhibitors. The trace residues identified by ET analysis are of great importance to study the structure-function relationship and also to guide the design of specific inhibitors.
Acyl Coenzyme A ; metabolism ; Acyltransferases ; chemistry ; genetics ; metabolism ; Amino Acid Sequence ; Animals ; Binding Sites ; Conserved Sequence ; Enzyme Inhibitors ; chemistry ; pharmacology ; Evolution, Molecular ; Humans ; Imidazoles ; chemistry ; pharmacology ; Models, Molecular ; Molecular Sequence Data ; Oligopeptides ; chemistry ; pharmacology ; Phylogeny ; Protein Structure, Tertiary ; Sequence Homology, Amino Acid

OBJECTIVETo evaluate the long-term effect of sodium glycididazole (CMNa) as a hypoxic radiosensitizer on the radiotherapy for nasopharyngeal carcinoma.

METHODSBetween May 1999 and May 2002, 211 patients with pathologically confirmed nasopharyngeal carcinoma were randomized into group-A treated by radiotherapy plus CMNa or group-B by radiotherapy alone. The staging was determined according to 92' Fuzhou staging systerm. The type, procession and dosage of radiotherapy were identical in both groups. The early adverse effect grade was assessed based on the CTC2.0 criteria and the late adverse effects were evaluated according to the RTOG/EORTC criteria. The median follow-up time was 52 months. All the data was analyzed by the SPSS 13.0 software. Characteristics and adverse events of these patients were compared between the two groups using t-test and the Wilcoxin rank sum test. Time-to-event curves were estimated using the Kaplan-Meier method. The prognostic parameters were analyzed using univariate analysis and the Cox multivariate regression analysis.

RESULTSThe clinical data of the two groups were comparable. The 3-year survival was 88.4% in group-A, while 75.2% in group-B, with a statistically significant difference between two groups (P = 0.010). Univariate analysis showed that the 3-year survival was statistically correlated with N-staging ((N0-1, 86.9%, N2-3 73.8%, P < 0.001), T-staging (T1-2 85.6%, T3-4 79.3%, P = 0.014), TNM staging (P = 0.039), and whether using CMNa or not during rediotherapy (Group-A 88.4%, Group-B 75.2%, P = 0.010). The 5-year recurrence-free survival, 5-year metastasis-free survival and 5-year overall survival were 75.8%, 74.9% and 77.7% in Group-A, while 63.0%, 63.0% and 62.4% in Group-B with a statistically significant difference between two groups (0.013, 0.022 and 0.010, respectively). If stratified in the subgroups, the overall survival of stage III - IV patients was statistically different between group A and B (P = 0.009), however, not of stage I - II patients (P = 0.502). Cox multivariate regression analysis showed that the independent prognostic parameters for survival were N-stage (RR = 3.288) , T-stage (RR = 2.147) and use of CMNa during rediotherapy (RR = 0.407). However, there was no statistically significant difference between two groups in acute or late adverse effects on nervous system or heart, which suggested that use of CMNa during radiotherapy would not aggravate the toxicity caused by radiotherapy.

CONCLUSIONSodium glycididazole is well tolerable effective as a hypoxic radiosensitizer, which can improve the efficacy of radiotherapy and the long-term result of nasopharyngeal carcinom a patients, especially for the stage III - IV patients.

Adolescent ; Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Male ; Metronidazole ; adverse effects ; analogs & derivatives ; therapeutic use ; Middle Aged ; Multivariate Analysis ; Nasopharyngeal Neoplasms ; pathology ; radiotherapy ; Neoplasm Staging ; statistics & numerical data ; Prognosis ; Proportional Hazards Models ; Radiation-Sensitizing Agents ; adverse effects ; therapeutic use ; Time Factors ; Treatment Outcome ; Vomiting ; chemically induced