Objective: To investigate the risk factors for airway mucus hypersecretion in childhood pneumonia infected by different pathogens. Method: A retrospective cohort included 968 children who were hospitalized for Mycoplasma pneumoniae pneumonia (MPP), respiratory syncytial virus (RSV) pneumonia, adenovirus pneumonia and underwent bronchoscopy in Respiratory Department of Children's Hospital of Chongqing Medical University from January 2019 to December 2021 was conducted. The children were divided into two groups distinguished by airway mucus secretion according to the airway mucus hypersecretion score which were scored according to the mucus secretion under the bronchoscope. The demographic characteristics, clinical characteristics, laboratory tests and disease severity of the two groups were compared. And the risk factors for the development of airway mucus hypersecretion in two groups were analyzed. Chi square test, Mann-Whithey U test and Fisher exact test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the influencing factors. Result: There were 559 males and 409 females in the 968 children, with an age of 4.0 (1.4, 6.0) years. Among the 642 children with MPP, 185 cases were in the hypersecretion group and 457 cases were in the non-hypersecretion group. There were 41 cases in the hypersecretion group and 160 cases in the non-hypersecretion group of 201 children with RSV pneumonia. In the 125 children with adenovirus pneumonia, there were 39 cases in the hypersecretion group and 86 cases in the non-hypersecretion group. In these children, the age of children in the hypersecretion group was older than that in the non-hypersecretion group (6.0 (4.0, 7.0) vs. 5.0 (3.0, 7.0) years old, 1.5 (0.5, 3.6) vs. 0.8 (0.4, 1.6) years old, 2.0 (1.2, 4.5) vs. 1.3 (0.8, 2.0) years old, U=35 295.00, 2 492.00, 1 101.00, all P<0.05). Through multivariate Logistic regression analysis it found that increased risk of airway mucus hypersecretion was present in childhood MPP with increase in peripheral blood white blood cell count (OR=3.30, 95%CI 1.51-7.93, P=0.004) or increase in neutrophil ratio (OR=2.24, 95%CI 1.16-4.33, P=0.016) or decrease in lymphocyte count (OR=3.22, 95%CI 1.66-6.31, P<0.001) or decrease in serum albumin (OR=2.00, 95%CI 1.01-3.98, P=0.047). The risk of airway mucus hypersecretion was increased in children with RSV pneumonia combined with elevated peripheral blood eosinophils (OR=3.04, 95%CI 1.02-8.93, P=0.043). Meanwhile, airway mucus hypersecretion was associated with severe pneumonia (OR=2.46, 95%CI 1.03-6.15, P=0.047) in children with RSV pneumonia. Older age was associated with increased risk of airway mucus hypersecretion in children with adenovirus pneumonia (OR=1.02, 95%CI 1.00-1.04, P=0.026). In these children with occurrence of pulmonary rales, wheezes or sputum sounds (OR=3.65, 95%CI 1.22-12.64, P=0.028) had an increased risk of airway mucus hypersecretion. Neutrophils in bronchoalveolar lavage fluid (BALF) demonstrated higher ratio in hypersecretion group from children with MPP (0.65 (0.43, 0.81) vs. 0.59 (0.34, 0.76), U=24 507.00, P<0.01), while the proportion of macrophages in BALF was lower (0.10 (0.05, 0.20) vs. 0.12 (0.06, 0.24), U=33 043.00, P<0.05). Nucleated cell count and neutrophil ratio in BALF were higher in hypersecretion group of children with RSV pneumonia (1 210 (442, 2 100)×10⁶ vs. 490 (210, 1 510)×10⁶/L, 0.43 (0.26, 0.62) vs. 0.30 (0.13, 0.52), U=2 043.00, 2 064.00, all P<0.05). Conclusions: The increase in peripheral blood white blood cell count, neutrophil ratio and decrease in lymphocyte count, serum albumin in children with MPP is related to the development of airway mucus hypersecretion. In children with RSV pneumonia, the abnormal increase of eosinophils in peripheral blood has relationship with hypersecretion. The appearance of lung rale, wheezing, and sputum rale are associated with airway mucus hypersecretion in children with adenovirus pneumonia. In addition, local neutrophil infiltration in the respiratory tract is closely related to the occurrence of airway mucus hypersecretion caused by Mycoplasma pneumoniae and RSV infection.
Child ; Male ; Female ; Humans ; Infant ; Child, Preschool ; Retrospective Studies ; Respiratory Sounds ; Pneumonia, Mycoplasma ; Lung ; Respiratory Syncytial Virus Infections ; Mucus ; Pneumonia, Viral ; Risk Factors

Gut dysbiosis,a well-known risk factor to triggers the progression of Alzheimer's disease(AD),is strongly associated with metabolic disturbance.Trimethylamine N-oxide(TMAO),produced in the dietary choline metabolism,has been found to accelerate neurodegeneration in AD pathology.In this study,the cognitive function and gut microbiota of TgCRND8(Tg)mice of different ages were evaluated by Morris water maze task(MWMT)and 16S rRNA sequencing,respectively.Young pseudo germ-free(PGF)Tg mice that received faecal microbiota transplants from aged Tg mice and wild-type(WT)mice were selected to determine the role of the gut microbiota in the process of neuropathology.Excessive choline treatment for Tg mice was used to investigate the role of abnormal choline metabolism on the cognitive functions.Our results showed that gut dysbiosis,neuroinflammation response,Aβ deposition,tau hyper-phosphorylation,TMAO overproduction and cyclin-dependent kinase 5(CDK5)/transcription 3(STAT3)activation occurred in Tg mice age-dependently.Disordered microbiota of aged Tg mice accelerated AD pathology in young Tg mice,with the activation of CDK5/STAT3 signaling in the brains.On the contrary,faecal microbiota transplantation from WT mice alleviated the cognitive deficits,attenuated neuro-inflammation,Aβ deposition,tau hyperphosphorylation,TMAO overproduction and suppressed CDK5/STAT3 pathway activation in Tg mice.Moreover,excessive choline treatment was also shown to aggravate the cognitive deficits,Aβ deposition,neuroinflammation and CDK5/STAT3 pathway activation.These findings provide a novel insight into the interaction between gut dysbiosis and AD progression,clarifying the important roles of gut microbiota-derived substances such as TMAO in AD neuropathology.

OBJECTIVE: To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial. METHODS: A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC_0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored. RESULTS: Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC_0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000). CONCLUSION SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).
Alkaloids ; Blood Glucose ; Diabetes Mellitus, Type 2/drug therapy* ; Double-Blind Method ; Glycated Hemoglobin A ; Humans ; Hypoglycemic Agents/therapeutic use* ; Morus ; Tablets/therapeutic use* ; Treatment Outcome

Objective: To observe the effect of poloxamer 188 (P188) on megakaryocyte cultivation and induction from cord blood mononuclear cells in order to obtain more megakaryocyte progenitor cells (MPC). Methods: The cord blood mononuclear cells were isolated and inoculated in cell culture bag or cell culture flask respectively. The WIGGENS shaker and cell culture bags were used to mimick WAVE Bioreactor for three-dimensional (3D) cell culture, and the P188 was added to induction medium, The cells were detected for morphology, surface marker, viability, and number on day 14. Results: In the two-dimensional (2D) culture, CD41(+), CD41(+)/CD61(+), CD61(+) megakaryocytic numbers increased significantly after adding P188 (all P<0.01). And in the 3D culture of adding P188, the cell volume became larger and the nuclear shape was irregular, the cytoplasm appeared magenta granules, and the megakaryocyte cells became more mature. By 3D culture, the expression of CD41/CD61 was (36.30±1.27)% vs (23.95±1.34)%, hence the differentiation for MPC was significantly higher than that in the 2D group (P<0.01). Furthermore, adding P188 in 3D culture resulted in highest differentiation efficiency for MPC [(59.45±1.20)%]. There were no significantly differences in terms of cell viability and cell number among 3D culture containing P188, 2D and 3D culture groups (all P>0.05). Conclusion: 3D culture was beneficial for the differentiation of MPC, but the cell viability was lower than 2D group; However, the satisfied cell growth and better induction efficiency were obtained by adding of P188, which might provide a new method of megakaryocytes production for clinical application.
Bioreactors ; Cell Differentiation ; Cells, Cultured ; Fetal Blood ; Megakaryocytes ; Poloxamer

OBJECTIVETo explore the clinical value and efficacy of reduced field intensity modulated radiation therapy (RF-IMRT) for patients with advanced cervical cancer.

METHODSSeventy-one patients with stage IIB-IIIB cervical cancer, who underwent reduced field IMRT (RF-IMRT group) and 72 patients treated with conventional radiotherapy (c-RT group) in Shandong Cancer Hospital between 2005 August and 2011 August, were enrolled in this study. The RF-IMRT plans were as follows: whole pelvic IMRT plan was performed to deliver an initial dose of 30 Gy, then the irradiated volume was reduced to lymphatic drainage region as well as paracervix and parametrium for an additional 30 Gy boost. Conventional 2-field RT plan was performed in these patients using ADAC Pinnacle 3 planning system, to be given the same prescription dose, and to compare the irradiation dose of organs at risk (OARs). At the same time, conventional 2-field RT was performed in 72 patients of the c-RT group. Concurrent chemotherapy and intracavitary brachytherapy were also performed in the two groups. The treatment response, toxicities, normal tissue avoidance, and survival were assessed.

RESULTSSixty-six patients of the RF-IMRT group and 65 patients of the c-RT group fulfilled the treatment plan. IMRT plans yielded better dose conformity to the target (0.711 ± 0.057 vs. 0.525 ± 0.062, P = 0.032) and better sparing of the rectum, bladder and small intestine (rectum: 41.6 ± 6.8 vs. 50.8 ± 3.2, P = 0.016; bladder: 40.2 ± 2.9 vs. 51.4 ± 1.8, P = 0.007; small intestine: 22.3 ± 2.6 vs. 35.8 ± 3.9, P = 0.004). The mean dose delivered to the planning target volume (PTV) was significantly higher in the RF-IMRT group than that in the c-RT group (60.8 vs. 51.2 Gy, P = 0.006). The RF-IMRT patients experienced significantly lower acute and chronic toxicities with comparable short-term effects than did those treated with conventional RT (P > 0.05). No significant differences were found between the two groups for 1-, 3-, and 5-year overall survival (OS) rates, while a significantly higher progression-free survival (PFS, 65.2% vs. 46.2%, P = 0.031) rate was observed in the RF-IMRT group.

CONCLUSIONSRF-IMRT yields higher dose distributions and lower toxicities compared with conventional RT, and both the tumor target volume and pelvic lymphatic drainage region achieve curative dose irradiation, the adjacent organs at risk are well protected, and with tolerable adverse reactions. Yet, RF-IMRT provides comparable clinical outcomes and higher PFS.

Adenocarcinoma ; drug therapy ; pathology ; radiotherapy ; Brachytherapy ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; radiotherapy ; Chemoradiotherapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Staging ; Organs at Risk ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Intensity-Modulated ; adverse effects ; methods ; Remission Induction ; Survival Rate ; Uterine Cervical Neoplasms ; drug therapy ; pathology ; radiotherapy

Objective To detect the expression of hypoxia inducible factor 1 alpha (HIF-1α),glucose transporter protein-1 (GLUT-1) and vascular endothelial growth factor (VEGF) in human laryngeal carcinoma tissue,and to study the relationship between hypoxia and HIF-1α,GLUT-1,VEGF in human laryngeal carcinoma Hep-2 cells and to explore the effect of HIF-1α,GLUT-1 and VEGF as endogenous hypoxic markers on laryngeal carcinoma.Methods The expression levels of HIF-1α,GLUT-1 and VEGF were detected in 35 cases of laryngeal carcinoma by SP immunohistochemical methods and in Hep-2 cells by SP immunocytochemical methods.The relationship between HIF-1 α and GLUT-1,VEGF protein expression was analyzed.Results Of the 35 cases,16 cases expressed HIF-1α,16 cases expressed GLUT-1,19 cases expressed VEGF.The expression of HIF-1α and VEGF were closely correlated with pathologic grading and lymphnode metastasis.GLUT-1 was correlated with lymphnode metastasis.The expression levels of HIF-1 α,GLUT-1 and VEGF in Hep-2 cells under hypoxic condition were higher than those under normoxiccondition.Conclusion HIF-1α may promote the expression of GLUT-1 and VEGF in laryngeal carcinoma,furthermore promote tumor angiogenesis,invasion,and metastasis of the laryngeal carcinoma.

Objective To study whether laryngeal cancer stem cells in hypoxia have the characteristic of resistance to irradiation and underlying mechanism.Methods CD133 + cells were separated from Hep-2 cells with flow cytometry(FCM)and the purity was 92.8％.The separated CD133 + cells were cultured in serum-free medium in hypoxia in normoxia enviroment respetively,and hypoxiainducible factor 1 alpha(HIF-1α)expression was detected by FCM.The cells were exposed respectively to X-rays emitted by linear accelerator with a dose of 0,5,10,15 or 20 Gy for 24 hours,with additional time points of 12,36,and 48 hours for the cells exposed to 10 Gy.Then the growth inhibition ratios of ceils in hypoxia and normoxia groups were detected with MTT assay at different time points.Soft agar colony formation assay was used to dectect colony formation ratios of cells in hypoxia and normoxia groups.DNA dependent protein kinase catalytic subunit(DNA-PKcs),ataxiatelangiectasia mutate(ATM),Survivin and P53 were detected by FCM.Results Growth inhibition ratio of CD133 + cells in hypoxia group was lower than that in normoxia group(P ＜0.05).Colony formation ratio of CD133 + cells was higher than that of CD133-cells(P ＜ 0.01)and the ratio of CDi33 + cells in hypoxia group was higher than that in nonnoxia group(P ＜0.05).The ratio of hypoxia group was not affected by irradiation,while the ratio of normoxia group decreased significantly after irradiation(P ＜ 0.05).The expressions of DNA-PKcs,ATM,Survivin and P53 in CD133+ cells were higher than those in CD133-cells respectively(P ＜0.01).In CD133 + cells with radiation,the expressions of DNA-PKcs and Survivin of hypoxia group were higher those of normoxia group(P ＜ 0.05),but no difference in the expression of ATM or P53 between the two groups.Conclusions Laryngeal cancer stem cells play an important role in radioresistance mediated by hypoxia.

Objective To explore overweight and obesity on pulmonary function,exercise tolerance,quality of life in COPD.Methods Patients with COPD were divided into three groups:normal body mass index (BMI) (n =43),overweight (n =34) and obese (n =36).Resting pulmonary function test,cardiopulmonary exercise test (CPET) and St George' s respiratory questionnaire (SGRQ) scores were compared during all three classes of BMI.SPSS13.0 software was used.Results Normal BMI patients (47.28±3.82)％ had less FEV1/FVC compared to overweight ( 52.50 ± 8.23 ) ％ and obese (53.20 ± 8.30) ％,and the difference has statistically significance (F =8.76,P ＜0.01 ).There were significant differences in FEV1/FVC between normal BMI patients and obese (P ＜ 0.01 ),normal BMI patients and overweight(P ＜ 0.01 ),but not between obese and overweight (P ＞ 0.05) by multiple comparison.VO2 max/kg in normal group was (21.80 ± 3.67 ) ml · kg-1 · min-1,(20.19 ±4.14) ml · kg 1 · min- 1 in overweight group and (18.98 ± 3.22)ml · kg-1 · min-1 in obese group,and the differences among the three group were significant (F =5.82,P ＜ 0.01 ).Multiple comparison showed no difference between normal and overweight ( P ＞ 0.05 ),between overweight and obese group (P ＞ 0.05 ),but difference was significant between normal and obese (P ＜0.05) ; There was no difference in SGRQ score (P ＞0.05).Conclusions Weight excess may improve the airflow obstruction of resting pulmonary function test,but exercise tolerance and the airflow obstruction of CPET were worse in obese and overweight.

OBJECTIVETo explore the effect of glutathione (GSH) and sodium selenite on the metabolism of arsenic in the liver, kidney and blood of mice exposed to iAsIII through drinking water.

METHODSThe mice were randomly divided into control, arsenic, GSH and sodium selenite group, respectively. And each group had eight mice and the mice were exposed to 50 mg/L arsenite by drinking water for 4 weeks. Mice were intraperitoneally injected with GSH (600 mg/kg) and sodium selenite (1 mg/kg) for seven days from the beginning of the fourth week. At the end of the fourth week, liver, kidney and blood were sampled to assess the concentrations of inorganic arsenic (iAs), monomethylarsenic acid (MMA), dimethylarsenic acid (DMA) by hydride generation trapping by ultra-hypothermia coupled with atomic absorption spectrometry.

RESULTSThe liver DMA (233.76 +/- 60.63 ng/g) concentration in GSH group was significantly higher than the arsenic group (218.36 +/- 42.71 ng/g). The concentration of DMA (88.52 +/- 30.86 ng/g) and total arsenic (TAs) (162.32 +/- 49.45 ng/g) in blood of GSH group was significantly higher than those [(45.32 +/- 12.19 ng/g), (108.51 +/- 18.00 ng/g), respectively] of arsenic groups(q values were 3.06, 6.40, 10.72 respectively, P < 0.05). The primary methylated index (PMI) (0.65 +/- 0.050) and secondary methylated index (SMI) (0.55 +/- 0.050) in liver sample of GSH group were significantly higher than those (0.58 +/- 0.056, 0.44 +/- 0. 093) in arsenic group. In blood samples, the PMI (0.85 +/- 0.066) in GSH group was significantly higher than that (0.54 +/- 0.113) in arsenic group (q values were 3.75, 5.26, 4.21 respectively, P < 0.05). However, no significant difference was identified between sodium selenite and arsenic groups in liver, kidney or blood samples. And no significant difference was detected in kidney samples among all arsenic exposing groups.

CONCLUSIONExogenous GSH could promote the methylated metabolism of iAsIII, but sodium selenite showed no significant effects.

Animals ; Arsenic ; analysis ; metabolism ; Arsenic Poisoning ; metabolism ; Environmental Exposure ; Female ; Glutathione ; pharmacology ; Male ; Mice ; Mice, Inbred Strains ; Sodium Selenite ; pharmacology ; Water Supply