[One case of severe exogenous lipoid pneumonia complicated with lung abscess caused by diesel inhalation].

Exogenous lipoid pneumonia is an inflammatory response to the lungs caused by inhaled lipid substances, which is prone to secondary bacterial infection, resulting in the formation of local abscesses, which can be life-threatening in severe cases. This paper reports a case of a 55-year-old patient with diesel aspiration, secondary to Klebsiella pneumoniae (ESBL positive) and Candida glabrata infection resulting in lung abscess formation. He was treated with a variety of antibacterial drugs for anti-infection, non-invasive ventilator ventilation, bronchoalveolar lavage, glucocorticoids, phlegm and other medical treatments. Finally, he underwent middle lobectomy for improvement and was discharged from the hospital, and he recovered well with regular follow-up.

[A case of corrosive digestive tract and lung injury caused by ingestion of pipeline dredging agent].

Ingestion of corrosive substances can severely burn the upper digestive tract leading to bleeding or perforation, and may even be life-threatening. Less commonly, damage to the trachea and bronchi is involved. In this paper, a case of corrosive digestive tract injury and lung injury after oral administration of pipeline dredging agent (the main components are hydroxide, sodium carbonate, sodium hypochlorite, etc.) was analyzed. After active rescue treatment, the patient died of massive hemoptysis. It is suggested that serious complications may occur after ingestion of corrosive substances. Timely diagnosis and reasonable medical management are needed to improve the level of recognition and treatment of such diseases.

[Retrospective analysis of short-term curative effect of total laparoscopic loop ileostomy reversal after radical resection of rectal cancer].

Objective: To investigate the safety, feasibility and short-term efficacy of total laparoscopic loop ileostomy reversal in patients after resection of rectal cancer. Methods: The clinical data of 20 patients who underwent total laparoscopic loop ileoscopic loop ileostomy after radical resection of rectal cancer at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, or Beijing Chaoyang District Sanhuan Cancer Hospital from October 2019 to June 2020 were collected and retrospectively analyzed. Results: All patients had successfully underwent total laparoscopic ileostomy reversal without conversion to open surgery or discontinued operation. No perioperative related death cases were found. In the whole group, the median operation time was 97 (60-145) minutes and the median intraoperative blood loss was 20 (10-100) milliliters. The median Visual Analogue Scale (VAS) score was 1.9 (1-5) one day after the operation. Nobody needed to use additional analgesic drugs. The median time to grand activities was 25 (16-42) hours, the median time to flatus was 44 (19-51) hours, and the median hospitalization after operation was 6.9 (5-9) days. No patients underwent operation related complications such as operative incision infection, abdominal and pelvic infection, intestinal obstruction, anastomotic leakage, bleeding and so on. Conclusions: Total laparoscopic loop ileostomy reversal appears to be safe, feasible and with promising efficacy for selected patients.

[Research progress of relationship between vitamin K and type 2 diabetes].

Objective: To systematically review research on the association between vitamin K and type 2 diabetes and diabetes-related biomarkers in humans, and evaluate the role of vitamin K in the prevention of type 2 diabetes. Methods: "Vitamin K", "type 2 diabetes" and related terms were searched in PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang Med Online up to November 2018. Results: A total of 1 Chinese and 12 English articles were included. Among 6 observational studies, 5 of them showed that higher dietary vitamin K intake and plasma vitamin K level were associated with the decrease of the risk of type 2 diabetes. Among 6 clinical intervention studies, 5 of them indicated that the supplementation of vitamin K(1) or K2 could have positive influence on insulin metabolism. One Mendelian randomization study showed higher circulation vitamin K level might reduce the risk of type 2 diabetes. Conclusion: Vitamin K plays an important role in the prevention and control of type 2 diabetes, which may be related to the improvement of insulin metabolism and blood glucose level.

Gender and time delays in diagnosis of pulmonary tuberculosis: a cross-sectional study from China.

Gender inequality has severe consequences on public health in terms of delay in diagnosis of pulmonary tuberculosis (PTB). In order to explore gender-related differences in diagnosis delay, a cross-sectional study of 10 686 patients diagnosed with PTB in Yulin from 1 January 2009 to 31 December 2014 was conducted. Diagnosis delay was categorised into 'short delay' and 'long delay' by four commonly used cut-off points of 14, 30, 60 and 90 days. Logistic regression analysis was used to analyse gender differences in diagnostic delay. Stratified analyses by smear results, age, urban/rural were performed to examine whether the effect persisted across the strata. The median delay was 31 days (interquartile range 13-65). Diagnostic delay in females at cut-off points of 14, 30, 60 and 90 days had odds ratios (OR) of 0.99 (95% CI 0.91-1.09), 1.09 (95% CI 1.01-1.18), 1.15 (95% CI 1.05-1.26) and 1.18 (95% CI 1.06-1.31), respectively, compared with males. Stratified analysis showed that females were associated with increased risk of longer delay among those aged 30-60 years, smear positive and living in the rural areas (P < 0.05). The female-to-male OR increased along with increased delay time. Further inquiry into the underlying reasons for gender differences should be urgently addressed to improve the current situation.

Research on changes in cognitive function, ß-amyloid peptide and neurotrophic factor in stroke patients.

OBJECTIVE: To investigate the changes as well as the related mechanism in cognitive function and levels of serum ß-amyloid peptide (Aß) and brain-derived neurotrophic factor (BDNF) in stroke patients. PATIENTS AND METHODS: A total of 30 patients with acute stroke treated in our hospital from June 2015 to September 2016 were selected as stroke group, while 30 volunteers during the same period were enrolled as control group. Changes in cognitive function of patients were evaluated using the Montreal Cognitive Assessment (MoCA) and mini-mental state examination (MMSE) before and after the treatment. At the same time, the concentrations of serum Aß1-40 and BDNF were detected, and their correlations with the MMSE score were analyzed. Finally, levels of serum cyclic adenosine monophosphate (cAMP) and phosphorylated-cAMP-response element binding protein (p-CREB), and the phosphorylation level of Tau protein were detected by Western blotting. RESULTS: MoCA and MMSE scores of patients in stroke group were significantly lower than those in control group (p < 0.01), and the scores were significantly higher in stroke patients after treatment than those before treatment (p < 0.01). Compared with those in control group, the serum Aß1-40 concentration in patients in stroke group was significantly increased (p < 0.01), but the BDNF level was significantly decreased (p < 0.01). Compared with those before treatment, the serum Aß1-40 concentration in patients was significantly decreased after treatment (p < 0.01), but the BDNF concentration was significantly increased (p < 0.01). Correlation analysis showed that the MMSE score was negatively correlated with the concentration of Aß1-40 (r2 = 0.764, p < 0.01), but positively related to the level of BDNF (r2 = 0.827, p < 0.01). Compared with those in control group, the content of serum cAMP and p-CREB in stroke patients was significantly decreased (p < 0.01), but the expression of p-Tau was statistically increased (p < 0.01). CONCLUSIONS: The cognitive function in stroke patients is impaired, with the rising content of serum Aß1-40 and reduction of BDNF, the mechanism of which is related to the decrease of cAMP and p-CREB and the increase of p-Tau. This provides a theoretical basis for searching the new therapeutic targets and new drugs for stroke.

[The relationship between smoking and hyperuricemia in Chinese residents].

Objective: To explore the relationship between smoking and hyperuricemia in Chinese residents. Methods: Based on data from the China Health and Nutrition Survey (CHNS), residents with blood samples provided in the 2009 round (including information of socio-demographic factors, lifestyle behaviors, medical history, and laboratory examinations etc.) were selected as the participants in the current analysis. Unconditional logistic regression models were utilized to compute the ORs and corresponding 95%CIs for assessing the relationship between smoking and hyperuricemia. Results: Among the 8 785 subjects, 1 435 had hyperuricemia with a prevalence rate of 16.3%, consisting of 886 men and 549 women with prevalence rates of 21.6% (886/4 110) and 11.7% (549/4 675) , respectively. Compared with never smokers, the adjusted OR (95%CI) for hyperuricemia was 0.83 (0.70-0.98) among current smokers, 0.77 (0.63-0.94) among current smokers with 20-39 years of smoking, and 0.79 (0.65-0.97) among current smokers with 11-20 cigarettes per day. When stratified by gender and compared with non-smoker, the adjusted OR (95%CI) for hyperuricemia among current smokers compared with never smokers was 0.83 (0.70-0.98) among men, while no significant association was found in female current smokers (OR=0.73, 95%CI: 0.42-1.26, P=0.260). Conclusion: In Chinese residents, there is an inverse association between smoking and hyperuricemia prevalence, and this association may be related to duration and intensity of smoking among current smokers. The findings need to be validated in large prospective cohort studies.

Cartilage-specific deletion of Alk5 gene results in a progressive osteoarthritis-like phenotype in mice.

OBJECTIVE: Previous studies have shown that Transforming growth factor-ß (TGF-ß)/TGFßRII-Smad3 signaling is involved in articular cartilage homeostasis. However, the role of TGF-ß/ALK5 signaling in articular cartilage homeostasis has not been fully defined. In this study, a combination of in vitro and in vivo approaches was used to elucidate the role of ALK5 signaling in articular cartilage homeostasis and the development of osteoarthritis (OA). DESIGN: Mice with inducible cartilage-specific deletion of Alk5 were generated to assess the role of ALK5 in OA development. Alterations in cartilage structure were evaluated histologically. The expressions of genes associated with articular cartilage homeostasis and TGF-ß signaling were analyzed by qRT-PCR, western blotting and immunohistochemistry. The chondrocyte apoptosis was detected by TUNEL staining and immunohistochemistry. In addition, the molecular mechanism underlying the effects of TGF-ß/ALK5 signaling on articular cartilage homeostasis was explored by analyzing the TGF-ß/ALK5 signaling-induced expression of proteoglycan 4 (PRG4) using specific inhibitors. RESULTS: Postnatal cartilage-specific deletion of Alk5 induced an OA-like phenotype with degradation of articular cartilage, synovial hyperplasia, osteophyte formation, subchondral sclerosis, as well as enhanced chondrocyte apoptosis, overproduction of catabolic factors, and decreased expressions of anabolic factors in chondrocytes. In addition, the expressions of PRG4 mRNA and protein were decreased in Alk5 conditional knockout mice. Furthermore, our results showed, for the first time, that TGF-ß/ALK5 signaling regulated PRG4 expression partially through the protein kinase A (PKA)-CREB signaling pathway. CONCLUSIONS: TGF-ß/ALK5 signaling maintains articular cartilage homeostasis, in part, by upregulating PRG4 expression through the PKA-CREB signaling pathway in articular chondrocytes.

Isolation and characterization of cancer stem cells from medulloblastoma.

Brain cancer stem cells are a subset of tumor cells present in several types of brain tumor that evade treatment regimens and are responsible for tumor recurrence. Recent reports on several tumors have suggested that Hoechst 33342 dye exclusion is a powerful technique for isolating cancer stem cell-like side population (SP) cells. In the present study, we attempted to isolate the SP cells from medulloblastoma, a malignant brain tumor in children. The tumor samples obtained were subjected to fluorescence-activated cell sorting analysis for SP cell isolation. Further, the SP cells were characterized by a sphere-formation assay and analyzed for expression of stem cell genes by reverse transcription-polymerase chain reaction (RT-PCR). Using flow cytometry, we isolated 2.9% of cancer stem-like SP cells from malignant medulloblastoma, which was reduced to 0.4% in the presence of verapamil, an inhibitor of ABC transporter. These SP cells undergo rapid proliferation and have a high tendency to form tumor spheres when compared with non-SP cells. Further, RT-PCR analysis revealed that the isolated SP cells have increased expression of neural stem cell markers such as nestin, Notch1, and the ABC transporter protein ABCG2. Therefore, our findings suggest that SP cells of medulloblastoma share the characteristics of cancer stem cells. The increased expression of stem cell markers and ABCG2 protein may function collectively and be responsible for drug and apoptosis resistance, as well as tumor recurrence and invasion.

Impact of diabetes on diagnostic delay for pulmonary tuberculosis in Beijing.

SETTING: Delays in the diagnosis of pulmonary tuberculosis (PTB) increase the risk of transmission and severity of the disease. Little information is available on PTB patients with diabetes mellitus (DM). OBJECTIVES: To examine the impact of DM on delays in diagnosing PTB and the effect of diagnostic delay on the clinical presentation of PTB among patients in Beijing, China. DESIGN: In a cross-sectional study conducted in two PTB dispensaries of Beijing, all confirmed PTB patients were screened for DM. Data relating to diagnostic delay and clinical presentation of PTB were collected and analysed. RESULTS: Of 1126 PTB patients selected, 182 (16.2%) were identified as having DM. The median delay for PTB patients with DM (25 days) was significantly higher than that of PTB patients without DM (6 days). In a subgroup analysis, diagnostic delay was associated with smear positivity among PTB patients with DM (OR 3.10, 95%CI 1.66-5.76) and associated with smear positivity (OR 4.38, 95%CI 3.19-6.04), pulmonary cavities (OR 2.62, 95%CI 1.85-3.71) and more symptoms (OR 1.81, 95%CI 1.20-2.73) among PTB patients without DM. CONCLUSIONS: DM was associated with longer diagnostic delays, which in turn was associated with more serious clinical presentations of PTB. It is thus necessary to examine risk factors associated with diagnostic delay among PTB patients with and without DM.

PP-1α and PP-1γ display antagonism and differential roles in tumorigenicity of lung cancer cells.

Protein serine/threonine phosphatases are important cellular signaling molecules and play major roles in regulating many different functions including cell proliferation, senescence, programmed cell death, and oncogenic cell transformation. Among different serine/threonine phosphatases, PP-1 and PP-2A contribute to more than 90% phosphatase activities in eukaryotes. While the functions of PP-2A in cell transformation and tumorigenesis have been well established, the role of PP-1 in carcinogenesis remains to be further explored. Moreover, PP-1 exists in different isoforms, whether these isoforms have differential functions in tumorigenesis remains to be examined. In the present study, we demonstrated that in lung cancer 1299 cells, PP1α and PP- 1 & γ exist in an antagonizing balance. In the parent H1299 cells, PP-1γ is dominant, about 4-fold higher than that of PP-1α. Overexpression of PP-1α significantly down-regulates PP-1γ at both mRNA and protein levels. In contrast, knockdown of PP-1α leads to upregulation of PP-1γ. Moreover, overexpression of PP-1α significantly attenuates the ability of the H1299 cells in promoting tumorigenicity as tested in immuno-deficient nude mice. This attenuation is derived from the halted cell cycle progression, which is largely attributed by the changed RB-E2F activity. Together, our results demonstrate that PP-1α and PP-1γ not only antagonize each other in lung cancer cells, but also display differential functions in tumorigenicity.

Protein serine/threonine phosphotase-1 is essential in governing normal development of vertebrate eye.

Protein serine/threonine phosphatase-1 (PP-1) is one of the key enzymes responsible for dephosphorylation in vertebrates. Protein dephosphorylation via PP-1 is implicated in many different biological processes including gene expression, cell cycle control, transformation, neuronal transmission, apoptosis, autophage and senescence. However, whether PP-1 directly controls animal development remains to be investigated. Here, we present direct evidence to show that PP-1 plays an essential role in regulating eye development of vertebrates. Using goldfish as a model system, we have shown the following novel results. First, inhibition of PP-1 activity leads to death of a majority of the treated embryos, and the survived embryos displayed severe phenotype in the eye. Second, knockdown of each catalytic subunit of PP-1 with morpholino oligomers leads to partial (PP-lα knockdown) or complete (PP-lß or PP-lγ knockdown) death of the injected embryos. The survived embryos from PP-1α knockdown displayed clear retardation in lens differentiation. Finally, overexpression of each subunit of PP-1 also causes death of majority of the injected embryos and leads to abnormal development of goldfish eye. Mechanistically, Pax-6 is one of the major downstream targets mediating the effects of PP-1 function since the eye phenotype in Pax-6 knockdown fish is similar to that derived from overexpression of PP-1. Together, our results for the first time provide direct evidence that protein phosphatase-1 plays a key role in governing normal eye formation during goldfish development.

The PP2A-Aß gene is regulated by multiple transcriptional factors including Ets-1, SP1/SP3, and RXRα/ß.

Protein phosphatase-2A (PP-2A) is a major serine/threonine phosphatase abundantly expressed in eukaryotes. PP-2A is a heterotrimer that contains a 65 kD scaffold A subunit, a 36 kD catalytic C subunit, and a regulatory B subunit of variable isoforms ranging from 54-130 kDs. The scaffold subunits, PP2A-Aα/ß, act as platforms for both the C and B subunits to bind, and thus are key structural components for PP-2A activity. Mutations in both genes encoding PP2A-Aα and PP2A-Aß lead to carcinogenesis and likely other human diseases. Our previous work showed that the gene coding for PP2A-Aα is positively regulated by multiple transcription factors including Ets-1, CREB, and AP-2α but negatively regulated by SP-1/SP-3. In the present study, we have functionally dissected the promoter of the mouse PP2A-Aß gene. Our results demonstrate that three major cis-elements, including the binding sites for Ets-1, SP1/SP3, and RXRα/ß, are present in the proximal promoter of the mouse PP2A-Aß gene. Gel mobility shifting assays reveal that Ets-1, SP1/SP3, and RXRα/ß all bind to PP2A-Aß gene promoter. In vitro mutagenesis and reporter gene activity assays demonstrate that while Ets-1 displays negative regulation, SP1/SP3 and RXRα/ß positively regulate the promoter of the PP2A-Aß gene. Co-expression of the cDNAs encoding Ets-1, SP1/SP3, or RXRα/ß and the luciferase reporter gene driven by PP2A-Aß promoter further confirm their control over the PP2A-Aß promoter. Finally, ChIP assays demonstrate that Ets-1, SP1/SP3, and RXRα/ß can all bind to the PP2A-Aß gene promoter. Together, our results reveal that multiple transcription factors regulate the PP2A-Aß gene. Moreover, our results provide important information explaining why PP2A-Aα and PP2A-Aß display distinct expression levels.

αA- and αB-crystallins interact with caspase-3 and Bax to guard mouse lens development.

The small heat shock protein, α-crystallin, exists in two isoforms, αA and αB, and displays strong ability against stress-induced apoptosis. Regarding their functional mechanisms, we and others have demonstrated that they are able to regulate members in both caspase and Bcl-2 families. In addition, we have also shown that αA and αB may display differential anti-apoptotic mechanisms under certain stress conditions. While αA-crystallin regulates activation of the AKT signaling pathway, αB negatively regulates the MAPK pathway to suppress apoptosis induced by UV and oxidative stress. Although previous studies revealed that αA and αB could regulate members in both caspase and Bcl-2 families, the molecular mechanism, especially the in vivo regulation still waits to be elucidated. In the present communication, we present both in vitro and in vivo evidence to further demonstrate the regulation of caspase-3 and Bax by αA and αB. First, Surface Plasmon Resonance (SPR) and yeast two-hybrid selection analysis demonstrate that αA and αB directly bind to caspase-3 and Bax with differential affinities. Second, immunohistochemistry reveals that αA and αB regulate caspase-3 and Bax at different developmental stages of mouse embryo. Third, coimmunoprecipitation shows that αA and αB form in vivo interacting complexes with caspase-3 and Bax. Together, our results further confirm that αA and αB regulate caspase-3 and Bax in vitro and in vivo to regulate lens differentiation.

In vitro mutagenesis of Xanthomonas campestris alpha-amylase gene by partially replacing deoxythymidine triphosphate with 5-bromo-2'-deoxyuridine-5'-triphosphate using a PCR technique.

Three mutants of the wild type alpha-amylase gene from Xanthomonas campestris pv. campestris 8004 were obtained using a PCR technique in which deoxythymidine triphosphate (dTTP) was partially replaced by 5-bromo-2'-deoxyuridine-5'-triphosphate (BrdUTP), at an optimal dTTP:BrdUTP ratio of 1000:1. Of thre three mutants that were obtained and which were sequenced, one mutant with 40 times higher activity than the wild type alpha-amylase gene product was obtained by using primary PCR products as a template for a second PCR reaction.

A baseline study on the importance of bovines for human Schistosoma japonicum infection around Poyang Lake, China.

We hypothesize that bovine infections are responsible for the persistence of human schistosomiasis transmission in the Yangtze marshlands of China. To test this hypothesis, we are carrying out a comparative intervention among four administrative villages in the Poyang Lake region, Jiangxi Province, two of which are experimental and two are control. The primary design involves treating, at the onset of the study, all the inhabitants in all four villages with praziquantel and all the bovines in two villages (the experimental or intervention villages). Following treatment, rates of reinfection in people of all villages, and in bovines in the experimental villages, will be assessed as will the ongoing prevalence of infection in bovines in the control villages. Before treatment, the prevalence and intensity of infection among humans and bovines was ascertained in the four villages. Our study design and baseline information are presented here, along with a description of the ecology of the study villages.

Phosphate prodrugs of PD154075.

In the preparation of phosphate prodrugs of PD154075, several strategies of linking a phosphate group to the indole moiety were studied. A novel linker, p-hydroxymethylbenzoyloxymethoxycarbonyl, was discovered to provide the phosphate prodrug of PD154075 (compound 9) with significantly increased aqueous solubility, sufficient stability in aqueous solution and good bio-reconversion in vivo.

Arterial baroreceptors control plasma vasopressin responses to graded hypotension in conscious dogs.

We studied the role of cardiac and arterial baroreceptors in the reflex control of arginine vasopressin (AVP) and renin secretion during graded hypotension in conscious dogs. The dogs were prepared with Silastic cuffs on the thoracic inferior vena cava and catheters in the pericardial space. Each experiment consisted of a control period followed by four periods of inferior vena caval constriction, during which mean arterial pressure (MAP) was reduced in increments of approximately 10 mmHg. The hormonal responses were measured in five dogs under four treatment conditions: 1) intact, 2) acute cardiac denervation (CD) by intrapericardial infusion of procaine, 3) after sinoaortic denervation (SAD), and 4) during combined SAD+CD. The individual slopes relating MAP to plasma AVP and plasma renin activity (PRA) were used to compare the treatment effects using a 2 x 2 factorial analysis. There was a significant (P < 0.01) effect of SAD on the slope relating plasma AVP to MAP but no effect of CD and no SAD x CD interaction. In contrast, the slope relating PRA and MAP was increased (P < 0.05) by SAD but was not affected by CD. These results support the hypothesis that stimulation of AVP secretion in response to graded hypotension is primarily driven by unloading arterial baroreceptors in the dog.

Stereoselective synthesis of Xaa psi[CH2CH(OH)]Yaa dipeptidomimetics and their inclusion in HIV-1 protease inhibitors.

Two stereoselective syntheses of a new pseudodipeptide isostere, the right-hand hydroxyethylene dipeptidomimetic (Xaa psi[CH2CH(OH)]Yaa), are presented. In one method readily available amino acids are used as starting materials for Evans chiral aldol condensation chemistry. The second method relies on the synthesis of an anti-aldol product for the hydroxyethylene isostere via an E-selective ethyl hydrocinnamate enolization, and thus allows for the synthesis of isosteres having side chains other than those available from amino acids. Both methods are illustrated by the chiral synthesis of Boc-Phe psi[CH2CH(OH)]Phe. Two diastereomers, (S,S,R) and (S,R,R), are incorporated into an HIV-1 protease inhibitor template which yields potent inhibitors of HIV-1 protease when the pseudodipeptide isostere is Phe psi[CH(OH)CH2]Phe or Phe psi[CH(OH)CH(OH)]Phe. The resulting Phe psi[CH2CH(OH)]Phe-containing inhibitors possess modest potency.

[Staining test with methylene blue during resection of bladder cancer in 30 patients].

From November 1991 to March 1993, staining test with methylene blue was applied in 30 patients with the bladder cancer during operation. Twelve patients (40%) showed positive results, and 27 specimens were obtained from the stained areas. Histological examination proved that they were carcinoma in situ (11), transitional cell carcinoma (7), squamous cell carcinoma (4), dysplasia (3), chronic cystitis (1), and normal mucosa (1). The positive rate of histological results was 96.3%. 21 specimens from the unstained areas showed negative results. Six (33%) of 18 patients with single tumor and 6 (50%) of 12 patients with multiple tumor were positively stained. Follow-up from 10 to 26 months showed one patient (3.3%) had recurrence after 8 months.