Objective:To investigate the effect of macrophage-derived exosomes on the morphological transformation of Candida albicans (CA), and to explore the underlying mechanisms.Methods:In vitro cultured human acute monocytic leukemia cell line THP-1 was induced and differentiated into M0 macrophages using the phorbol ester PMA. CA was activated and prepared as the fungal suspension. M0 macrophages were infected with the CA suspension, and the process of cell phagocytosis was observed under a high-content imaging analysis system. M0 macrophage-derived exosomes (exosome group) and CA-infected M0 macrophage-derived exosomes (CA exosome group) were extracted by differential centrifugation; transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis were performed to identify and compare exosomes in the two groups. The exosomes from the two groups were separately co-cultured with CA (exosome-treated group and CA exosome-treated group), and independently cultured CA served as the blank control group; the morphological changes of CA were observed under an inverted microscope, the intracellular cyclic adenosine monophosphate (cAMP) contents were detected by the enzyme-linked immunosorbent assay (ELISA), and the expression levels of cAMP-related genes, RAS1 and CDC35 (also known as Cyr1), were detected by real-time quantitative PCR (RT-qPCR) . Results:Western blot analysis showed that exosomes from the exosome group and CA exosome group both expressed the tumor susceptibility gene 101 protein (TSG101, an exosome marker), and did not express calnexin (a negative marker) ; transmission electron microscopy and nanoparticle tracking analysis showed no significant differences in the morphology or size of the exosomes between the two groups. Compared with the blank control group, the exosome-treated group and CA exosome-treated group both showed obvious inhibition of the yeast-to-mycelial phase transition of CA, with a noticeable reduction in the length of the hyphae under the inverted microscope. ELISA revealed that the intracellular cAMP content in CA significantly decreased in the exosome-treated group and CA exosome-treated group (16.70 ± 0.84 pmol/ml, 16.82 ± 0.87 pmol/ml, respectively) compared with the blank control group (21.82 ± 1.08 pmol/ml; t = 6.45, 6.23, respectively, both P = 0.003). RT-qPCR revealed that the expression of the cAMP-related genes, RAS1 and CDC35, was down-regulated in the exosome-treated group and CA exosome-treated group compared with the blank control group (all P < 0.01), and the RAS1 mRNA expression was significantly lower in the CA exosome-treated group than in the exosome-treated group ( t = 7.43, P = 0.002) . Conclusion:Both M0 macrophage-derived exosomes and CA-infected M0 macrophage-derived exosomes could effectively inhibit the mycelial growth of CA, and the latter one exhibited a stronger inhibitory effect, possibly by down-regulating cAMP in the cAMP/protein kinase A pathway.

Outpatient humanistic care refered to providing a full process of caring medical services to outpatients. In order to standardize the human caring services for outpatients in medical institutions, promote the comprehensive service level of outpatient services, and improve the patient′s medical experience, Chinese Association for Life Care issued the group standard of Management Norms for Human caring of Outpatients in April 2023. This standard clarified the relevant terms and definitions of human caring for outpatients, specified the basic requirements for human caring, the humanistic quality and care responsibilities of outpatient staff, the outpatient care environment and facilities, the outpatient care process and measures, and quality management. It designed standardized and personalized full process care service norms, providing references for medical institutions at all levels to promote the development of human caring for outpatients.

OBJECTIVE To explore the efficacy of alfacalcidol combined with conventional antihypertensive and lipid- lowering drugs on liver and kidney function， serum inflammatory cytokines and renin-angiotensin system（RAS） in hypertensive patients with renal impairment. METHODS A total of 200 hypertensive patients with renal impairment who were treated in the department of nephrology in our hospital from December 2017 to December 2020 were selected and randomly divided into control group and observation group， with 100 cases in each group. Both groups of patients were treated with conventional antihypertensive and lipid-lowering drugs for a total of 14 weeks， patients in the observation group were additionally treated with oral alfacalcidol after 2 weeks of treatment （0.25 μg each time， once a day， for a total of 12 weeks）. The levels of liver function indexes [aspartate aminotransferase （AST）， alanine aminotransferase （ALT）]， renal function indexes [blood calcium， blood phosphorus， blood urea nitrogen （BUN）， cystatin C （Cys-C）， serum creatinine （Scr）， urine microalbumin （mAlb）， β2-microglobulin （β2-MG）， urinary N- acetyl β-D-glucosaminidase （NAG）， 24 h urinary protein]， inflammatory factors [serum interleukin 6 （IL-6）， tumor necrosis factor α （TNF-α）， hypersensitive C-reactive protein （hs-CRP）] and RAS activity indexes [renin， angiotensin Ⅰ（Ang Ⅰ）， Ang Ⅱ and aldosterone] were observed in 2 groups before and after treatment， and the occurrence of adverse drug reactions was recorded during treatment. RESULTS There was no statistical significance in the levels of detection indexes between 2 groups before treatment （P＞0.05）. After treatment， the level of blood calcium in the observation group was significantly higher than before treatment （P＜0.05）， but remained at clinically normal level. Compared with before treatment， the levels of Cys-C， Scr， BUN， urine mAlb， β2-MG， NAG and 24 h urinary protein， hs-CRP， IL-6， TNF-α， renin， Ang Ⅰ， Ang Ⅱ and aldosterone were significantly decreased in the observation group after treatment （P＜0.05）. After treatment， the level of blood calcium in observation group was significantly higher than control group （P＜0.05）. Additionally， the levels of Cys-C， Scr， BUN，urine mAlb， β2-MG， NAG， 24 h urinary protein， hs-CRP， IL-6， TNF-α， renin， Ang Ⅰ， Ang Ⅱ and aldosterone were significantly lower than control group （P＜0.05）. There was no statistical significance in the incidence of adverse drug reactions between 2 groups during treatment （P＞0.05）. CONCLUSIONS Alfacalcidol combined with routine therapy of antihypertensive and lipid-lowering drugs could effectively improve liver and renal functions， inhibit inflammation and RAS activity in hypertensive patients with renal impairment， with a favorable safety.

AIM: To explore the possible mechanism of Xiaokeshu recipe in the treatment of type 2 diabetes mellitus (T2DM) by observing the effects of Xiaokeshu Recipe on serum inflammatory factors. METHODS: Male SPF-grade SD rats were fed with high-fat and high-sugar fodder combined with intraperitoneal injection of streptozotocin (STZ) to prepare the model of T2DM. The model rats were randomly divided into a model group,a metformin group, low and high-dose Xiaokeshu recipe groups, and a normal group was set up. After successful modeling, the metformin group and the Xiaokeshu recipe groups were treated with metformin and Xiaokeshu recipe by gavage respectively, normal saline was given by gavage in the normal group and the model group. The general living status of rats before and after treatment was observed. After 4 weeks of drug intervention, serum samples and ileum tissue of rats were collected for biochemical and Western blot. RESULTS: As compaed with the model group,the polydipsia and polyuria in the low and high-dose Xiaokeshu recipe and the metformin groups could be improved. As compaed with the model group, the levels of fasting blood glucose (FBG), fasting insulin (FINS) and interleukin-1β (IL-1β) of rats in the low-dose Xiaokeshu recipe group were decreased, but the differences were statistically insignificant (P0.05), the levels of FBG, FINS and IL-1β of rats in the high-dose Xiaokeshu recipe and the metformin groups were significantly decreased as compared with the the model group (P 0.05 or P0.01). As compaed with the model group, the levels of Lipopolysaccharide (LPS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the high-dose Xiaokeshu recipe and the metformin groups were decreased (P<0.05 or P<0.01). As compared with the model group, the expressions of toll-like receptor 4 (TLR4) and nuclear transcription factor (NF-κB) protein in ileal tissue were down-regulated in the low and high-dose Xiaokeshu Recipe and the metformin groups (P<0.05 or P<0.01). CONCLUSION: Xiaokeshu recipe may reduce the level of serum LPS, inhibit the TLR4/NF-κB signaling pathway, and reduce the release of inflammatory factors, thus improving insulin resistance and reducing the blood sugar of the body.

Objective:To explore the effect of nurse-led multidisciplinary collaborative nutrition management on cancer patients.Methods:Using the convenient sampling method, 106 cancer patients in Henan Provincial People's Hospital from January 2019 to December 2020 were selected as the research objects. According to the admission time, the patients were divided into two groups. A total of 51 patients admitted from January to December 2019 were selected as the control group, while 55 patients admitted from January to December 2020 were selected as the research group. The control group was given routine nutrition intervention, while the research group was given nurse-led multidisciplinary nutrition management on the basis of the control group. Nutritional grading and Quality of Life Instruments for Cancer Patients-Core Module (EORTC QLQ-C30) scores before and after intervention were compared between the two groups. The target achievement of nutritional management and the occurrence of gastrointestinal adverse reactions were counted.Results:After intervention, nutrition of the research group was better than that of the control group and EORTC QLQ-C30 score was higher than that of the control group, and the differences were statistically significant ( P<0.05) . The achievement rate of nutrition management goals in the research group was 67.27% (37/55) , higher than 39.22% (20/51) in the control group, and the difference between the two groups was statistically significant ( P<0.05) . The incidence of gastrointestinal adverse reactions in the research group was 3.64% (2/55) , lower than 17.65% (9/51) in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:The implementation of nurse-led multidisciplinary collaborative nutrition management in cancer patients can improve their nutritional status and quality of life, increase the rate of achieving nutritional management goals and reduce the incidence of gastrointestinal adverse reactions.

As an important platform compound, 3-hydroxypropionic acid (3-HP) can be used as a substrate to synthesize a variety of biological products with commercial potential. The titer of 3-HP by wild-type bacteria is low, which severely limits the large-scale application and production of 3-HP. By modifying the genes related to the metabolic pathway, engineered bacteria using cheap substrates as carbon sources are constructed, the aim of reducing production cost and increasing output is realized. In this paper, the recent progress in the synthesis of 3-HP by metabolic engineering at home and abroad is reviewed. The advantages and disadvantages of glycerol pathway, malonyl-CoA pathway and beta-alanine pathway for synthesis of 3-HP are also summarized and analyzed, and the future development of 3-HP is prospected.
Glycerol ; metabolism ; Industrial Microbiology ; trends ; Lactic Acid ; analogs & derivatives ; biosynthesis ; Metabolic Engineering ; Metabolic Networks and Pathways ; genetics

Objective: To assess the role of activated platelets in the inflammatory procession of atherosclerosis(AS) by ultrasound molecular imaging. Methods: Sixty ApoE-/- mice were fed with high fat diet to establish AS model as experimental group, and 40 C57BL/6J mice were fed with normal diet as control group. Biotin-avidin bridging method was used to construct platelet-targeted microbubbles with recombinant vWF-A1 domain (Mb-A1), microbubbles carrying monoclonal antibodies to VCAM-1 (Mb-VCAM1) and microbubbles carrying IgG monoclonal antibody (Mb-ctrl). In vitro and in vivo experiments were carried out to evaluate the ability of Mb-A1 to target platelets on vascular endothelial surface. Contrast enhanced ultrasound molecular imaging of proximal ascending aorta was performed with Mb-A1, Mb-VCAM1 and Mb-ctrl. The expression and distribution of platelets and monocytes/macrophages on the endothelium of ascending aorta of AS mice were observed and analyzed by immunofluorescence staining. Results: ①A large number of Mb-A1 adhering to the surface of activated platelets coated in Petri dishes were observed under fluoresce. ②After platelet immune-depletion in 30-week AS mice, the signal intensity of Mb-A1 decreased significantly in ascending aorta, while that of Mb-ctrl has no obvious change(P<0.05). ③In ApoE-/- mice, signals from platelet targeted microbubbles increased from 8 to 32 weeks of age in ApoE-/- mice, which coincided with the increase of signals from VCAM-1 targeted microbubbles(P<0.05). ④Activated platelets on the endothelial surface of ascending aorta increased progressively with age from 8 weeks, and partly overlapped with the distribution of monocytes/macrophages. Conclusions Platelets contribute to the initiation and progression of atherosclerosis as an inflammatory mediator through the interaction with vascular endothelium.

Objective To investigate the clinical efficacy and safety of high-dose caspofungin (70 mg/d)as initial or salvage treatment for invasive pulmonary aspergillosis.Methods Twenty-one patients with proven or probable invasive pulmonary aspergillosis from June 2014 to October 2017 in Huashan Hospital,Fudan University were retrospectively reviewed.According to the anti-fungal treatment before high-dose caspofungin application,patients were divided into initial treatment group and salvage treatment group.Patients' clinical data and laboratory data were collected.The characteristics,clinical efficacy,adverse reactions,one-year survival rate and the overall effective rate were evaluated.The prognosis of the two groups was compared by Kaplan-Meier analysis.Results Twenty of the 21 patients opportunistic acquired invasive pulmonary aspergillosis during the treatment of underlying diseases.Five patients were initially treated with high-dose caspofungin for 68 (62) days.At week 12,one patient achieved complete response,3 patients achieved partial response,and the overall effective rate was 80％ (4/5).Sixteen patients received caspofungin as salvage therapy for 66.50 (58) days,of which one patient got complete response at week 12,10 had partial response,and the overall effective rate was 68.75％ (11/16).One-year follow-up showed that no patient died in the initial treatment group,and the one-year survival rate was 100％ (5/5).In salvage treatment group,3 patients died of pulmonary bacterial infections and the one-year survival rate was 81.25％ (13/16).During treatment,one patient had elevated total bilirubin,which was possibly associated with high-dose caspofungin.Conclusions High-dose caspofungin regimen has good efficacy and safety,both for initial treatment and salvage therapy in patients with invasive pulmonary aspergillosis.

Objective: To investigate the impact of blood pressure and age on arterial stiffness in general population. Methods: Participants who took part in 2010, 2012 and 2014 Kailuan health examination were included. Data of brachial ankle pulse wave velocity (baPWV) examination were analyzed. According to the WHO criteria of age, participants were divided into 3 age groups: 18-44 years group (n=11 608), 45-59 years group (n=12 757), above 60 years group (n=5 002). Participants were further divided into hypertension group and non-hypertension group according to the diagnostic criteria for hypertension (2010 Chinese guidelines for the managemengt of hypertension). Multiple linear regression analysis was used to analyze the association between systolic blood pressure (SBP) with baPWV in the total participants and then stratified by age groups. Multivariate logistic regression model was used to analyze the influence of blood pressure on arterial stiffness (baPWV≥1 400 cm/s) of various groups. Results: (1)The baseline characteristics of all participants: 35 350 participants completed 2010, 2012 and 2014 Kailuan examinations and took part in baPWV examination. 2 237 participants without blood pressure measurement values were excluded, 1 569 participants with history of peripheral artery disease were excluded, we also excluded 1 016 participants with history of cardiac-cerebral vascular disease. Data from 29 367 participants were analyzed. The age was (48.0±12.4) years old, 21 305 were males (72.5%). (2) Distribution of baPWV in various age groups: baPWV increased with aging. In non-hypertension population, baPWV in 18-44 years group, 45-59 years group, above 60 years group were as follows: 1 299.3, 1 428.7 and 1 704.6 cm/s, respectively. For hypertension participants, the respective values of baPWV were: 1 498.4, 1 640.7 and 1 921.4 cm/s. BaPWV was significantly higher in hypertension group than non-hypertension group of respective age groups (P<0.05). (3) Multiple linear regression analysis defined risk factors of baPWV: Multivariate linear regression analysis showed that baPWV was positively correlated with SBP(t=39.30, P<0.001), and same results were found in the sub-age groups (t-value was 37.72, 27.30, 9.15, all P<0.001, respectively) after adjustment for other confounding factors, including age, sex, pulse pressure(PP), body mass index (BMI), fasting blood glucose (FBG), total cholesterol (TC), smoking, drinking, physical exercise, antihypertensive medications, lipid-lowering medication. (4) Multivariate logistic regression analysis of baPWV-related factors: After adjustment for other confounding factors, including age, sex, PP, BMI, FBG, TC, smoking, drinking, physical exercise, antihypertensive medication, lipid-lowering medication, multivariate logistic regression analysis showed that risks for increased arterial stiffness in hypertension group were higher than those in non-hypertension group, the OR in participants with hypertension was 2.54 (2.35-2.74) in the total participants, and same results were also found in sub-age groups, the ORs were 3.22(2.86-3.63), 2.48(2.23-2.76), and 1.91(1.42-2.56), respectively, in each sub-age group. Conclusion SBP is positively related to arterial stiffness in different age groups, and hypertension is a risk factor for increased arterial stiffness in different age groups. Clinical Trial Registry Chinese Clinical Trial Registry, ChiCTR-TNC-11001489.