China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI) to Prevent Cognitive Decline: Study Design and Progress.

BACKGROUND: Alzheimer's disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately. MEDTODS: We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60-80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application. RESULTS: Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025. CONCLUSIONS: This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.

[Progress and prospects of liquid-liquid phase separation in developmental diseases].

Membrane-bound organelles as well as membrane-free compartments exist in eukaryotic cells, which divide the nucleus and cytoplasm into distinct subregions and allow specific biochemical reactions to occur. The physiological mechanisms of membrane-bound organelles have been extensively characterized, but the formation and function of membrane-free compartments have not been thoroughly studied. Over the past decade, significant progress had been made in the studies about the role of liquid-liquid phase separation (LLPS) in the formation of membrane-free organelles. LLPS which serves as an aggregated separation mechanism for cellular biochemical reactions, is associated with a variety of physiological processes such as signal transduction and gene transcriptional regulation; while aberrant LLPS may contribute to the occurrence of developmental diseases. The present review investigates the role of LLPS as a mechanism of aggregation and segregation of cellular biochemical responses. The mechanisms of LLPS development and recent advances in the relationships between aberrant LLPS and developmental diseases are forward discussed, as well as how these advances may aid in the development of LLPS-based therapies.

[Investigation of familial tendency of endometriosis].

Objective: To investigate the familial heritability of endometriosis and to compare the clinical characteristics of patients with or without a family history of endometriosis. Methods: From January 2020 to June 2022, 850 patients with endometriosis confirmed by laparotomy or laparoscopy in Peking University Third Hospital were included in this study. Clinical data were collected, family history was followed up, and the differences of clinical indicators between patients with and without family history of endometriosis were compared. Results: A total of 850 patients were enrolled, with an average age of (33.8±7.0) years old, 315 (37.1%, 315/850) patients in stage Ⅲ and 496 (58.4%, 496/850) patients in stage Ⅳ. There were 100 patients with family history of endometriosis, accounting for 11.8% (100/850). Most of the 113 relatives involved were mothers, daughters and sisters (76.1%, 86/113), 81.5% (22/27) of the second and third degree relatives were maternal relatives. The median ages of patients with and without family history of endometriosis were 30 and 33 years old respectively at the time of diagnosis. The unmarried rate of patients with family history was higher [42.0% (42/100) vs 26.3% (197/750)]. The percentage of dysmenorrhea patients with family history was higher [89.0% (89/100) vs 55.5% (416/750)]. The medians of dysmenorrhea score in patients with and without family history were 6 and 2, and the median durations of dysmenorrhea were 10 and 1 years. There were significant differences in age, marital status, percentage of dysmenorrhea, dysmenorrhea score and duration (all P<0.001). The median levels of serum cancer antigen (CA) 125 in patients with family history and patients without family history at the time of diagnosis were 57.5 and 46.9 kU/L respectively, with a statistically significant difference (P<0.05). However, there were no significant differences between the two groups in nationality, bady mass index, menarche age, menstrual cycle, menstrual period, menstrual volume, serum CA19-9 level, cyst location and size, stage, history of adverse pregnancy and childbirth, infertility, adenomyosis and deep infiltrating endometriosis (all P>0.05). By comparing the specific conditions of dysmenorrhea patients with and without family history of endometriosis, there were no significant differences between the two groups in terms of the age of onset of dysmenorrhea, duration of dysmenorrhea, primary and secondary dysmenorrhea, and progressive aggravation of dysmenorrhea (all P>0.05). The difference in the degree of dysmenorrhea in dysmenorrhea patients with family history of endometriosis was significant (P<0.001). Conclusions: The incidence of endometriosis has a familial tendency, and most of the involved relatives are the first degree relatives. Compared with patients without family history of endometriosis, endometriosis patients with family history are diagnosed at an earlier age, with higher percentage of dysmenorrhea, had more severe dysmenorrhea and higher serum CA125 level.

[Factors influencing bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt].

Objective: To investigate the factors influencing total bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt (TIPS). Methods: 104 cases with portal hypertension and esophageal variceal hemorrhage (EVB) treated with elective TIPS treatment were selected as the study subjects and were divided into a bilirubin-elevated group and a normal bilirubin group according to the total bilirubin elevation level during the early postoperative period. Univariate analysis and logistic regression were used to analyze the factors influencing total bilirubin elevation in the early postoperative period. PCR amplification and first-generation sequencing technology were used to detect the polymorphic loci of the UGT1A1 gene promoter TATA box, enhancer c.-3279 T > G, c.211G > A, and c.686C > A. Logistic regression was used to analyze the correlation of four locus alleles and genotypes with elevated total bilirubin in the early postoperative period. Results: Among the 104 cases, 47 patients were in the bilirubin elevated group, including 35 males (74.5%) and 12 females (25.5%), aged (50.72 ± 12.56) years. There were 57 cases in the normal bilirubin group, including 42 males (73.7%) and 15 females (26.3%), aged (51.63 ± 11.10) years. There was no statistically significant difference in age (t = -0.391, P = 0.697) and gender (χ(2) = 0.008, P = 0.928) between the two groups of patients. Univariate analysis revealed that preoperative alanine transaminase (ALT) level (χ(2) = 5.954, P = 0.015), total bilirubin level (χ(2) = 16.638, P < 0.001), MELD score (χ(2) = 10.054, P = 0.018), Child-Pugh score (χ(2) = 6.844, P = 0.022), and postoperative portal vein branch development (χ(2) = 6.738, P = 0.034) were statistically significantly different between the two groups. Logistic regression analysis showed that preoperative ALT level, total bilirubin level, and portal vein branch development after TIPS were correlated with the elevated total bilirubin in the early postoperative period. The polymorphism of the c.211G > A locus of the UGT1A1 gene correlation had elevated total bilirubin in the early postoperative period of TIPS. The risk of elevated total bilirubin was increased in the population carrying allele A (P = 0.001, OR = 4.049) in the early postoperative period. Allelic polymorphisms in the TATA box promoter region and enhancer c.-3279 T > G and c.686C > A had no statistically significant difference between the bilirubin-elevated group and the normal bilirubin group. Conclusion: The preoperative ALT level, total bilirubin level, and portal vein branch development are correlated with the elevated total bilirubin in early postoperative patients. The polymorphisms of the UGT1A1 gene and enhancer c.211G > A are correlated with the occurrence of elevated total bilirubin in the early postoperative period of TIPS. Allele A carrier may have a higher risk of elevated total bilirubin in the early postoperative period.

Lurbinectedin for the treatment of small cell lung cancer.

Small cell lung cancer (SCLC) is a rapidly progressive, aggressive metastatic and lethal subtype of lung cancer. Unfortunately, there has been little progress regarding the development of novel treatments for SCLC. However, lurbinectedin, a transcriptional inhibitor, has emerged as a potential novel treatment for cancer. It produces antitumor efficacy by inhibiting oncogenic transcription activity, inducing the accumulation of DNA double-strand breaks and modulating the tumor microenvironment (TME). Data from phase I/II trials indicates that lurbinectedin has significant antitumor efficacy and tolerable adverse effects in SCLC patients. Furthermore, lurbinectedin is efficacious in platinum-sensitive and platinum-resistant SCLC patients and in those with SCLC relapse after second-line treatment. In 2020, the U.S. Food and Drug Administration (FDA) approved lurbinectedin for the treatment of adult patients with metastatic SCLC or for patients that have received platinum-based chemotherapy. In this review, we discuss the molecular profile and the preclinical and clinical studies of lurbinectedin in the treatment of SCLC patients.

Tepotinib hydrochloride for the treatment of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the most devastating cancers with high mortality worldwide. By inhibiting the activity of specific molecular targets in the cancer cells, tyrosine kinase inhibitors (TKIs) have become a standard treatment in combating NSCLC. Tepotinib hydrochloride is an orally bioavailable, mesenchymal-epithelial transition (MET) TKI developed mainly for selected NSCLC patients with METex14 skipping mutations. Tepotinib demonstrated durable clinical response in phase II clinical trials, which led to its approval for use in Japan and breakthrough therapy designation and accelerated approval in the U.S. These progresses highlighted tepotinib as a promising candidate for NSCLC patients. This review summarizes the pharmacological profile of tepotinib, preclinical studies and landmark clinical trials of tepotinib. In addition, we share our perspectives on the future direction of tepotinib as a novel anticancer drug.

MiR-329-3p inhibits hepatocellular carcinoma cell proliferation and migration through USP22-Wnt/ß-Catenin pathway.

OBJECTIVE: MicroRNA-329-3p (miR-329-3p) has been shown to be involved in tumor development. But its role in hepatocellular carcinoma has not been explored. Our study aims to explore the effect and mechanism of miR-329-3p on hepatocellular carcinoma development. PATIENTS AND METHODS: Hepatocellular carcinoma tissues and paired paracancerous specimens from 31 hepatocellular carcinoma patients undergoing surgery were collected. Quantitative real-time polymerase chain reaction and Western blot were employed to measure genes expression at mRNA and protein level. CCK-8 and transwell assays were performed to evaluate hepatocellular carcinoma cells proliferation and migration. Dual-Luciferase reporter gene assay was designed to validate the target gene of miR-329-3p. RESULTS: Our study showed miR-329-3p expression was significantly lower in hepatocellular carcinoma tissue. MiR-329-3p mimic inhibits proliferation and migration of HepG2 cells. By using Dual-Luciferase reporter gene assay, we proved that miR-329-3p inhibited HepG2 cell proliferation and migration by targeting USP22 directly. By up- and downregulation of USP22 expression, we also proved that USP22 can activate the Wnt/ß-Catenin pathway, which in turn affected the proliferation and migration of HepG2 cells. CONCLUSIONS: We demonstrated that miR-329-3p can inhibit HepG2 cell proliferation and migration by inhibiting USP22-Wnt/ß-Catenin pathway. Our study provides novel insights into the aetiology and potential treatment of hepatocellular carcinoma.

Attenuation of a virulent swine acute diarrhea syndrome coronavirus strain via cell culture passage.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly identified enteric alphacoronavirus that causes fatal diarrhea in newborn piglets in China. Here, we propagated a virulent strain SADS-CoV/CN/GDWT/2017 in Vero cells for up to 83 passages. Four strains of SADS-CoV/GDWT-P7, -P18, -P48 and -P83 were isolated and characterized. Sequence alignments showed that these four novel strains exhibited 16 nucleotide mutations and resultant 10 amino acid substitutions in open reading frame 1a/1b, spike, NS3a, envelope, membrane and nucleocapsid proteins. Furthermore, a 58-bp deletion in NS7a/7b was found in P48 and P83 strains, which led to the loss of NS7b and 38 amino acid changes of NS7a. Pig infection studies showed that the P7 strain caused typical watery diarrhea, while the P83 strain induced none-to-mild, delayed and transient diarrhea. This is the first report on cell adaption of a virulent SADS-CoV strain, which gives information on the potential virulence determinants of SADS-CoV.

A rare case of thoracic spinal intradural extramedullary enterogenous cyst with acute onset: case report and literature review.

The intraspinal enterogenous cyst, also called an neurenteric cyst, is a rare congenital disease. It was reported to be local to the C1 to L2 spinal segments, with the majority located in the cervicothoracic region. Most patients present with symptoms of progressive focal pain, myelopathic signs or radicular symptoms. We report a rare case of thoracic spinal intradural extramedullary enterogenous cyst with rapidly progressive weakness of both lower extremities. Additionally, we analysed the literature concerning the clinical features, diagnosis and prognosis of this disease.

Effect of rituximab combined with chemotherapy on the expression of serum exosome miR-451a in patients with diffuse large b-cell lymphoma.

OBJECTIVE: The aim of this study was to investigate the influence of rituximab combined with chemotherapy on the expression of serum exosome micro ribonucleic acid 451a (miR-451a) in patients with diffuse large B-cell lymphoma (DLBCL), and to explore the possible underlying mechanism. PATIENTS AND METHODS: 89 DLBCL patients (DLBCL group) receiving rituximab combined with chemotherapy were enrolled in this study. Meanwhile, 48 healthy controls (control group) were enrolled as well. Serum samples were collected from all patients before and after treatment, respectively. At the same time, blood samples of healthy people were collected, and serum exosome was extracted. Real-Time fluorescence-quantitative Polymerase Chain Reaction (qRT-PCR) was applied to measure the expression level of serum exosome miR-451a. Receiver operating characteristics (ROC) curve was used to evaluate the diagnostic efficiency of miR-451a. Statistical Product and Service Solutions (SPSS) 22.0 was employed for statistical analysis. Two-sided 95% confidence interval (CI) was used for all tests, and p<0.05 was considered statistically significant. RESULTS: The expression level of miR-451a in the DLBCL group was significantly lower than that of the control group. The area under the ROC curve (AUC) for the diagnostic efficacy of serum exosome miR-451a for DCBCL was 0.7147. After treatment, the level of serum exosome miR-451a in patients was significantly increased, whereas was still lower than the normal level. The AUC of ROC for evaluating the effect of serum exosome miR-451a in DCBCL was 0.8038. CONCLUSIONS: Serum exosome miR-451a has moderate diagnostic efficiency for DLBCL. Moreover, miR-451a can act as an indicator for evaluating the efficacy of rituximab combined with chemotherapy in the DLBCL treatment.

[Soft-tissue angiosarcoma with pulmonary metastases: case report and literature review].

Objective: To investigate the differential diagnosis between pulmonary metastases from soft-tissue angiosarcoma and primary pulmonary angiosarcoma. Methods: A case of soft-tissue angiosarcoma with pulmonary metastases was reported and related literatures were reviewed. Results: A 39 year-old man complaining of hemoptysis, cough, and sputum for 10 months was admitted to our hospital in September 2013. He was initially diagnosed as having primary pulmonary angiosarcoma after wedge-resection biopsy of the lung. After 22 months since onset, he felt discomfort in his leg, which led to the confirmative diagnosis of soft-tissue angiosarcoma of the leg with multiple pulmonary metastases by a full-body PET/CT scan and core needle biopsy of the leg. Twenty-three articles concerning primary pulmonary angiosarcoma with complete records of history, treatment and follow-up of patients were included in the literature review. A total of 26 patients were reported in these articles, including 18 males, 8 females, age 19-85 years, average (52±18) years. Primary pulmonary angiosarcoma was mainly manifested as single or multiple pulmonary nodules or masses, with or without ground glass opacity. In our case, chest CT showed multiple thin-wall cysts and ground glass opacities, and recurrent spontaneous pneumothorax, which had never been reported in literatures on primary pulmonary angiosarcoma. Conclusions: Pulmonary metastases from soft-tissue angiosarcoma differed from primary pulmonary lesions in terms of chest imaging, with the former usually showing thin-wall cysts and pneumothorax. A full-body PET-CT was essential for differential diagnosis between primary and metastatic pulmonary angiosarcoma.

Side-stream tobacco smoke-induced airway hyperresponsiveness in early postnatal period is involved nerve growth factor.

Epidemiological studies have shown that children are more susceptible to adverse respiratory effects of passive smoking than adults. The goal of this study is to elucidate the possible neural mechanism induced by exposure to passive smoking during early life. Postnatal day (PD) 2 and PD 21 mice were exposed to side-stream tobacco smoke (SS), a surrogate to secondhand smoke, or filtered air (FA) for 10 consecutive days. Pulmonary function, substance P (SP) airway innervation, neurotrophin gene expression in lung and nerve growth factor (NGF) release in bronchoalveolar lavage (BAL) fluid were measured at different times after the last SS or FA exposure. Exposure to SS significantly altered pulmonary function in PD2, accompanied with an enhanced SP innervation in airway. However, exposure to SS during the later developmental period (PD21) did not appear to affect pulmonary function and SP innervation of the airways. Interestingly, SS exposure in PD2 group significantly induced an increased gene expression on NGF, and decreased NGF receptor P75 in lung; parallel with high levels of NGF protein in BAL. Furthermore, pretreatment with NGF antibody significantly diminished SS-induced airway hyperresponsivenss and the increased SP airway innervation in the PD2 group. These findings suggest that enhanced NGF released in the lung contributes to SS-enhanced SP tracheal innervation and airway responsiveness in early life.

Circulating B7-H4 in serum predicts prognosis in patients with hepatocellular carcinoma.

B7-H4 is member of the B7 family that negatively regulates the immune response, which are important for fine-tuning of the tumor microenvironment. Dysregulation of B7-H4 expression has been associated with tumor progression. However, expression level of B7-H4 in hepatocellular carcinoma (HCC) tissues is still a controversial topic. In addition, whether serum B7-H4 expression of HCC patients has any clinical value is unknown. We compared serum levels of B7-H4 in patients with HCC and healthy controls by using the ELISA method. Association between serum B7-H4 expression level and clinical parameters of HCC was further investigated. Log-rank test and Kaplan-Meier method were employed to evaluate the overall survival rate of HCC patients. Univariate and multivariate analysis of prognostic factors were performed with the Cox regression model. Our results showed that HCC patients had significantly higher serum B7-H4 level as compared with healthy controls (P < 0.001). In addition, serum B7-H4 expression was correlated with HCC clinical parameters including serum AFP expression and TNM stage. HCC patients in the higher serum B7-H4 expression group had a poorer 5-year overall survival rate (P = 0.028). Moreover, serum B7-H4 expression was shown to be an independent prognostic factor for HCC (P = 0.034). The findings from this study suggest that serum B7-H4 is an independent prognostic indicator for HCC and may be a promising biomarker for early diagnosis as well as disease prognosis of HCC.

Investigation of the effects of single-nucleotide polymorphisms in DNA repair genes on the risk of glioma.

Several single-nucleotide polymorphisms (SNPs) in DNA repair gene have been shown to affect DNA repair and to modify susceptibility to cancer. In this study, to investigate the role of these SNPs in glioma, we examined the potential association of 14 SNPs in DNA repair genes with the glioma risk in a Chinese population. We included 326 glioma cases and 376 cancer-free controls. Genotyping of the 14 SNPs was performed on 384-well plates on the Sequenom MassARRAY platform. Of the 14 SNPs, rs1799782 and rs1799793 did not display the Hardy-Weinberg equilibrium in the control group. Moreover, the genotype distribution differed significantly between the two groups for the SNPs rs25487, rs3218536, and rs1799793. The rs25487 G/G genotype strongly and significantly increased the risk of glioma when compared with the rs25487 A/A genotype, indicated by an odds ratio (OR) = 2.23 [95% confidence interval (95%CI) = 1.36-3.87]. The rs25489 A/G genotype was also significantly associated with increased risk of glioma when compared with the A/A genotype (OR = 1.52; 95%CI = 1.03-2.35). In addition, rs1799782 increased the risk of glioma (OR = 1.89; 95%CI = 1.27-3.04), and a similar association was found for rs1800067 (OR = 1.89; 95%CI = 1.21-3.07). In conclusion, the results of our study suggest that the rs25487, rs25489, rs1799793, and rs13181 SNPs are associated with an increased risk of glioma. These findings may be useful for identifying the genetic factors involved in the development of glioma to help devise more efficient strategies to prevent this disease.

Clinical characteristics and treatment of superolateral dislocation of the mandibular condyle.

The aim of this retrospective study was to investigate the clinical characteristics of superolateral dislocation of the mandibular condyle, and to review our experience of its treatment. Thirteen patients were included in this study. Demographic information and details of their original injury were analyzed by descriptive statistics and the treatment methods were summarized. These patients could be classified into three types: (1) unilateral dislocation with isolated condylar fracture (n=3); (2) unilateral dislocation with associated condylar fracture and other mandibular fracture (n=7); (3) bilateral dislocation with associated condylar fracture and other mandibular fracture (n=3). Treatment involved three main aspects: (1) relief of the condylar dislocation by manual manipulation or open reduction; (2) reduction of the medial condylar fragment and fixation with screws, or removal of the fragment if less than 50% of the condylar width; however, in one case with a tiny condylar fragment, this was left in situ; (3) management of the other associated mandibular fractures by open reduction and internal fixation (ORIF). Follow-up ranged from 6 to 20 months (average 13.69 months). Satisfactory functional outcomes were achieved in these cases. The results of this study indicate that superolateral dislocation of the condyle assumes many forms, and the treatment depends on the presence of fractures.

Pharmacokinetics of florfenicol and its metabolite, florfenicol amine, in rice field eel (Monopterus albus) after a single-dose intramuscular or oral administration.

The pharmacokinetics of florfenicol (FF) and its metabolite, florfenicol amine (FFA), were studied in rice field eel (Monopterus albus) after a single dose (20 mg/kg) by intramuscular (i.m.) or oral gavage (p.o.) dose at 25 °C. The elimination half-lives (t1/2ß ), peak concentration of FF (Cmax ), and time to reach FF peak concentration (Tmax ) in plasma were estimated as 18.39 h, 10.83 µg/mL, and 7.00 h, respectively, after i.m. injection and 13.46 h, 8.37 µg/mL, and 5 h, respectively, after p.o. administration. The Tmax values of FF in tissues (i.e., kidney, muscle, and liver) were larger for i.m. injection compared with those for p.o. administration. The t1/2ß had the following order kidney>muscle>liver for i.m. administrated and kidney>liver>muscle for p.o. administrated. The largest area under the concentration-time curve (AUC) was calculated to be 384.29 mg·h/kg after i.m. dosing, and the mean residence time (MRT) was 42.46 h by oral administration in kidney. FFA was also found in all tissues with a lower concentration than FF for both i.m. and p.o. administrations throughout the study. The elimination of FFA was slow with a t1/2ß between 18.19 and 47.80 h in plasma and tissues. The mean metabolic rate of FFA for i.m. and p.o. administrations was >23.30%.

The diagnostic value of serum procalcitonin, IL-10 and C-reactive protein in community acquired pneumonia and tuberculosis.

AIM: To explore the diagnostic value of serum procalcitonin (PCT), interleukin-10 (IL-10), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in community acquired pneumonia (CAP) and tuberculosis (PTB). PATIENTS AND METHODS: 113 CAP cases patients and 78 PTB cases were enrolled from May 2011 to March 2012. Routine blood test, serum PCT, CRP, IL-10 and ESR of patients within 24 hours were analyzed retrospectively. RESULTS: The serum concentrations of PCT, IL-10, CRP and ESR in CAP patients with CAP were 0.35±0.017 mg/mL, 0.095±0.004 mg/L, 59.80±5.12 mg/L and 35.00±4.81 mm/1h, respectively, significantly higher than patients with PTB (p < 0.01); According to the result of ROC curve analysis in CAP and PTB, the PTC area under ROC curve is 0.715 (95% CI 0.647-0.782), the sensitivity and specific degree of serum PTC were significant better than CRP and IL10 (p < 0.05). In tuberculosis sputum culture, the serum concentrations of IL-10 and ESR in TB positive group were 0.045±0.013 mg/L and 62.50±8.69 mm/1h, significantly higher than that of TB negative group (p < 0.05); whereas, the concentrations of serum PCT and CRP in TB positive and negative groups had no significant difference (p > 0.05). CONCLUSIONS: The levels of serum PCT, IL-10, CRP and ESR in CAP patients are higher than that in PTB patients. Therefore, the serum PCT, IL10, CRP and ESR level is benefit to distinguish between CAP and PTB. This could provide a comprehensible evidence for both diagnosis and prognosis.

Early postnatal exposure of mice to side-steam tobacco smoke increases neuropeptide Y in lung.

Our recent study showed that prenatal and early postnatal exposure of mice to side-steam tobacco smoke (SS), a surrogate to environmental tobacco smoke (ETS), leads to increased airway responsiveness and sensory innervation later in life. However, the underlying mechanism initiated in early life that affects airway responses later in life remains undefined. The concomitant increase in nerve growth factor (NGF) after exposures suggests that NGF may be involved the regulation of airway innervation. Since NGF regulates sympathetic nerve responses, as well as sensory nerves, we extended previous studies by examining neuropeptide Y (NPY), a neuropeptide associated with sympathetic nerves. Different age groups of mice, postnatal day (PD) 2 and PD21, were exposed to either SS or filtered air (FA) for 10 consecutive days. The level of NPY protein in lung and the density of NPY nerve fibers in tracheal smooth muscle were significantly increased in the PD2-11SS exposure group compared with PD2-11FA exposure. At the same time, the level of NGF in lung tissue was significantly elevated in the PD2-11SS exposure groups. However, neither NPY (protein or nerves) nor NGF levels were significantly altered in PD21-30SS exposure group compared with the PD21-30FA exposure group. Furthermore, pretreatment with NGF antibody or K252a, which inhibits a key enzyme (tyrosine kinase) in the transduction pathway for NGF receptor binding, significantly diminished SS-enhanced NPY tracheal smooth muscle innervation and the increase in methacholine-induced airway resistance. These findings show that SS exposure in early life increases NPY tracheal innervation and alters pulmonary function and that these changes are mediated through the NGF.