Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners

Objective To explore the application effect of multi-disciplinary team(MDT)model in hospital antimi-crobial management.Methods Relevant data on antimicrobial use in hospitalized patients in a hospital from January 2021 to December 2022 were analyzed retrospectively,January-December 2021 adopted conventional management mode and was as the control group,January-December 2022 adopted MDT management model and was as the inter-vention group.Antimicrobial therapy relevant indicators between two groups of patients were compared.Results After adopting the MDT management model,pathogen detection rate before the therapeutic antimicrobial use in the intervention group(73.62％)was higher than that in the control group(70.56％),difference was statistically sig-nificant(P＜0.001).Pathogen detection rate related to healthcare-associated infection diagnosis was 87.98％in the control group and 88.89％in the intervention group,with no statistically significant difference between two groups(P＞0.05).Pathogen detection rate before combined use of key antimicrobial agents in the intervention group(93.94％)was higher than that in the control group(92.00％),difference was statistically significant(P＜0.05).Antimicro-bial use rate in hospitalized patients and use rate of prophylactic antimicrobial agents in class Ⅰ incision surgery de-creased from 38.03％and 21.03％to 32.78％and 10.30％,respectively,with statistically significant differences(both P＜0.05).The amount and intensity of antimicrobial use in hospitalized patients in the intervention group de-creased.The implementation rate of bundled prevention and control measures for multidrug-resistant organism(MDRO)after intervention was significantly higher than that of the control group,with statistically significant differences(all P＜0.05).MDRO detection rate decreased from 34.70％to 32.37％,difference was statistically significant(P=0.027).there was no significant change in the MDRO case infection rate.Conclusion The MDT model can effectively improve the standardized management of antimicrobial agents,promote the rational use of anti-microbial agents in clinical practice,and prevent bacterial resistance.

Abstract:Objective　To investigate the clinical characteristics and early diagnostic methods of patients with Talaromyces marneffei infection, so as to reduce the mortality of patients. Methods The clinical characteristics and microbiological analysis data including fungal culture, smear examination and mass spectrometry were collected from 18 patients with Talaromyces marneffei infection in the Department of Respiratory Medicine, Department of Tuberculosis, and Department of Critical Respiratory Medicine in Fuzhou Pulmonary Hospital from January 2017 to December 2021, and descriptive analysis was conducted. Results　All the 18 patients were confirmed to be infected with Talaromyces marneffei by conventional culture and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS). The main infection sites of 18 patients with Talaromyces marneffei infection were lungs and lymph nodes, and the patients were accompanied by clinical manifestations such as cough, sputum and fever. The imaging features such as patchy shadows, mediastinal lymph node shadows and nodular shadows were common. Microbiological testing showed a statistically significant difference between smear and culture with a higher positive culture rate (χ2=13.74, P<0.05). The positive rate of blood culture in microbiological test was 60.0% (9/15), the positive rate of bronchial lavage fluid culture was 26.7% (4/15), the positive rate of sputum culture was 5.6% (1/18), one case each of pus, bone marrow, pleural fluid and cerebrospinal fluid was positive for culture and the other cases were negative, one case of sputum and one case of pus were positive for smear and the rest were negative. Colony characteristics showed that the colony morphology was mycelial phase at 25 ℃, producing red pigment, and the branching pattern of the penicillus was seen microscopically as monoverticillate or biverticillate; At 35 ℃, the yeast phase appeared at the initial stage, and then the mycelium phase changed after 5-6 days; the yeast phase was observed at 37 ℃, and yeast-like cells were seen under the microscope. All 18 patients with Talaromyces marneffei infection got better after using antifungal drugs. Compared with non-HIV patients with Talaromyces marneffei infection, leukopenia and anemia were common in HIV patients with Talaromyces marneffei infection, and the differences were statistically significant (P<0.05). 　Conclusions The infection of Talaromyces marneffei can be divided into localized type and disseminated type, which usually invade the lungs, skin, lymph nodes and other places. The main manifestations of patients are fever, cough, phlegm and other atypical symptoms. At present, the diagnosis of Talaromyces marneffei infection is mostly based on the fungal culture test, and the application of MALDI-TOF MS method can effectively shorten the diagnosis time of Talaromycosis marneffei. Clinical characteristics combined with microbiological analysis provide an objective basis for early diagnosis of patients with Talaromyces marneffei infection, and timely use of antifungal therapy can improve the prognosis of patients.

It has been well documented that exercise can improve bone metabolism, promote bone growth and development, and alleviate bone loss. MicroRNAs (miRNAs) are widely involved in the proliferation and differentiation of bone marrow mesenchymal stem cells, osteoblasts, osteoclasts and other bone tissue cells, and regulation of balance between bone formation and bone resorption by targeting osteogenic factors or bone resorption factors. Thus miRNAs play an important role in the regulation of bone metabolism. Recently, regulation of miRNAs are shown to be one of the ways by which exercise or mechanical stress promotes the positive balance of bone metabolism. Exercise induces changes of miRNAs expression in bone tissue and regulates the expression of related osteogenic factors or bone resorption factors, to further strengthen the osteogenic effect of exercise. This review summarizes relevant studies on the mechanism whereby exercise regulates bone metabolism via miRNAs, providing a theoretical basis for osteoporosis prevention and treatment with exercise.
Humans ; MicroRNAs/metabolism* ; Osteogenesis/genetics* ; Cell Differentiation ; Osteoblasts ; Bone Resorption/metabolism*

ObjectiveTo explore the underlying mechanism of bile acids and metabolites as well as the key metabolic pathways and important endogenous targets in prehypertension. MethodThe metabolic mechanism of prehypertension was explored with non-targeted metabolomics combined with network analysis. The serum metabolomics of patients with prehypertension was analyzed by ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry. The relevant biological functions and signal targets were predicted and generated by network analysis. Finally，the predicted targets of this important pathway were verified by in vitro experiments，and the relevant information was verified by enzyme-linked immunosorbent assay （ELISA） and Western blot. ResultAs revealed by non-targeted metabolomics，there were 64 potential biomarkers and 13 metabolic pathways in the normal group，the prehypertension group， and the hypertension group. The results of network analysis and biological verification showed that the occurrence of prehypertension was related to vascular inflammation caused by the abnormal metabolism of bile acids and aromatic amino acids. Bile acid metabolism plays an important role in the occurrence and development of prehypertension by regulating the vascular inflammatory response. Amino acid N-acyltransferase，myeloperoxidase， and bile acid downstream receptor TGR5 are critical in the changes of the metabolic network. ConclusionIn prehypertension，bile acids are presumedly involved in regulating vascular inflammation， resulting in damage to blood vessels in prehypertension.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

OBJECTIVE: To explore the correlation between the changes of T lymphocyte subsets and cytokines in patients with MM and immune function status, biochemical indicators, and their relationships with clinical stage and prognosis, which is expected to provide a scientific basis for the prognosis analysis and condition monitoring of MM patients. METHODS: The clinical data of 89 MM patients in two hospitals were collected, and 36 healthy people without tumor or infectious diseases were selected as the control group. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) were used to detect the changes of core members of peripheral blood T lymphocyte subsets and cytokine levels, respectively. At the same time, automatic biochemical analyzer and automatic blood cell analyzer were used to detect serum β₂-microglobulin (β₂-MG), lactate dehydrogenase (LDH), albumin (ALB), creatinine (CRE) and hemoglobin (HGB) levels, and the relationship between T lymphocyte subsets and the above indexes and their clinical significance were analyzed. RESULTS: The proportions of NK cells and CD8⁺T lymphocytes in the peripheral blood of MM patients were significantly higher than that of the control group (P<0.01), the proportion of CD4⁺T and the ratio of CD4⁺/CD8⁺ were lower than those of the control group (P<0.05); however, there was no significant difference in the numbers CD3⁺T cells compared with the control group (P>0.05). The proportion of CD4⁺T and ratios of CD4⁺/CD8⁺ in MM patients were lower than those of normal controls, and were negatively correlated with MM staging (r=-0.964, r=-0.653), that is, the later the MM staging, the more obvious their levels were reduced, while CD8⁺T and NK cells were positively correlated with MM staging (r=0.891, r=0.728), that is, the later the MM staging, the more significant their levels increased. The levels of Treg cells (CD4⁺CD25^highCD127^low/-T cells/CD4⁺T cells) of MM patients in the disease stage Ⅰ, Ⅱ and Ⅲ were (5.87±0.92)%, (7.97±1.32)%, (11.52±4.71)% respectively, the difference was statistically significant compared with control group (P<0.05), and the level of Treg cells in MM patients with stage III was significantly higher than that in controls and patients with other disease stages (P<0.01). The proportion of Treg cells (CD4⁺CD25^highCD127^low/-T cells/CD4⁺T cells) in MM patients was positively correlated with the concentration of β₂-MG and LDH (r=0.793, r=0.536), but had no significant correlation with HGB, ALB and CRE. The serum levels of IL-6, IL-10 and TNF-α in MM patients were significantly higher than those in the control group (P<0.05), which were closely related to MM staging(r=0.839, r=0.917, r=0.746), that is, the later the MM staging, the higher the levels; The serum IFN-γ level was negatively correlated with the stage of MM (r=-0.689), and its level gradually decreased with the increase of the disease stage and degree (P<0.01). There was no significant correlation between the levels of IL-2 and IL-4 and the disease stage, but they were all up-regulated compared with the control group (P<0.05). CONCLUSION The abnormal regulation of the core members of T lymphocyte subsets and the levels of various cytokines are closely related to the disease progression and poor prognosis of MM patients, which is an effective indicator for the disease monitoring of MM patients.
Humans ; Multiple Myeloma/therapy* ; Cytokines ; L-Lactate Dehydrogenase ; T-Lymphocyte Subsets

Mycobacterium tuberculosis is the causative agent of tuberculosis(TB),which is still the leading cause of mortality from a single infectious disease worldwide.The development of novel anti-TB drugs and vaccines is severely hampered by the complicated and time-consuming genetic manipulation techniques for M.tuberculosis.Here,we harnessed an endogenous type Ⅲ-A CRISPR/Cas10 system of M.tuberculosis for efficient gene editing and RNA interference(RNAi).This simple and easy method only needs to transform a single mini-CRISPR array plasmid,thus avoiding the introduction of exogenous protein and minimizing proteotoxicity.We demonstrated that M.tuberculosis genes can be efficiently and specifically knocked in/out by this system as con-firmed by DNA high-throughput sequencing.This system was further applied to single-and multiple-gene RNAi.Moreover,we successfully performed genome-wide RNAi screening to identify M.tuberculosis genes regulating in vitro and intracellular growth.This system can be extensively used for exploring the functional genomics of M.tuberculosis and facilitate the development of novel anti-TB drugs and vaccines.

OBJECTIVE: To investigate the effects of high dose vitamin C on proliferation and apoptosis of acute myeloid leukemia (AML) cell lines including HL-60, U937 and primary CD34 leukemia cells in AML. METHODS: CD34 cells were sorted by using immunomagnetic cell sorting system, then the primary CD34 leukemia cells, including HL-60 and U937 cell lines were cultured in vitro. Cells in each group were treated with different concentrations of vitamin C, the survival rate of cells was determined by MTT assay, the apoptosis rate of cells was evaluated by Annexin V/PI double staining, the expression of apoptotic proteins-including cleaved caspase 3, cleaved caspase-9 and cleaved PARP were detected by Western blot. RESULTS: The proliferation of HL-60 and U937 cells could be inhibited by high dose vitamin C, which showed a concentration-dependent manner (r=-0.9664; r=-0.9796). HL-60 and U937 cells were treated with different concentrations of vitamin C (8 and 20 mmol/L) for 24 hours, respectively, it was found that with the increasing of vitamin C concentration, cell apoptosis rate was significantly increased (r=0.9905; r=0.9971), and the expression of apoptosis related proteins including cleaved caspase 3, cleaved caspase-9 and cleaved PARP was aslo significantly increased with the increasing of concentration. In addition, it was found that with or without the mutation of TET2, high dose vitamin C could inhibit the proliferation (r=-0.9719; r=-0.9699) and promote the apoptosis (r=0.9998; r=0.9901) of primary CD34 leukemia cells in AML, which showed a dose-dependent manner, but it showed no effect on the proliferation (r=-0.2032) and apoptosis (r=0.1912) of normal CD34 cells. CONCLUSION High dose vitamin C can inhibit the proliferation and promote the apoptosis of acute myeloid leukemia cells, and selectively kill primary CD34 leukemia cells in AML.
Apoptosis ; Ascorbic Acid ; Cell Proliferation ; HL-60 Cells ; Humans ; Leukemia, Myeloid, Acute ; U937 Cells

Objective::To observe the synergistic effect and mechanism of Yiqi Jianpi Huayu (YQJPHY) recipe combined with 5-fluorouracil (5-FU) on inhibiting gastric cancer growth, and investigate its possible mechanism through polarization direction of tumor-associated macrophages (TAMs) in tumor micro-environment. Method::A total of forty 615 mice were randomly divided into four groups including control group, YQJPHY(25 g·kg^-1) group, 5-FU (25 mg·kg^-1) group and combined group (YQJPHY plus 5-FU), with 10 mice in each group. The gastric cancer transplantation model was induced by axillary inoculation of MFC gastric cancer cells. Changes in tumor pathology were observed with hematoxylin-eosin staining (HE) method. The contents of M1 and M2 TAMs in tumor tissues were determined with flow cytometry, while the expression of CD206 in tumor was observed with immunohistochemistry. The mRNA expressions of TAM-related genes including interleukin-1β(IL-1β), interleukin-12(IL-12), tumor necrosis factor-α(TNF-α), arginase-1(Arg1), and chitinase 3-like 3(Ym1) were detected by using quantitative real-time polymerase chain reaction (Real-time PCR). Furthermore, the mRNA and protein expressions of epithelial-mesenchymal transition (EMT) related epithelial calcium adhesion protein(E-cadherin), nervous calcium adhesion protein(N-cadherin), Zinc finger transcription factor Slug, Snail and Waveform protein (Vimentin) were detected with Real-time PCR and Western blot, respectively. Result::The gastric cancer cells in tumors were distributed in nest and/or flaky shape, with fibroblastic connective tissue reaction and inflammatory cells infiltrated in interstitium. Coagulative necrosis of tumor was observed in various treatment groups. The amount of residual cancer cells in mouse was as follows from largest to smallest: control group>YQJPHY group>5-FU group>combined group. Immunohistochemical studies showed that all treatment groups can reduce the expression of CD206 in the tumor, and the effect was most obvious in the combined group. The contents of M2-TAM in all treatment groups were lower than those in control group(P<0.05, P<0.01), and the most significant difference in the content of M2-TAMs was shown between the control group and the combined group. The contents of M1 TAMs were increased in YQJPHY and combined groups(P<0.05, P<0.01), with the largest incremental range in YQJPHY group. The expressions of Arg1 and Ym1 in YQJPHY and combined groups were lower, while IL-1β, TNF-α and IL-12 levels were higher than those in control group(P<0.05). The mRNA expressions of IL-1β, IL-12 and TNF-α in the combined group were significantly higher, while Arg1 and Ym1 mRNA expression levels were lower than those in the 5-FU group(P<0.05). As compared with the control group, the mRNA and protein expression levels of E-cadherin were up-regulated(P<0.05), while the mRNA expression levels of N-cadherin and Vimentin were down-regulation in the YQJPHY group (P<0.05), E-cadherin mRNA and protein expression levels were up-regulated, while N-cadherin, Slug, Snail, Vimentin mRNA expression as well as N-cadherin and Slug protein expression levels were down-regulated in the combined group(P<0.05). As compared with the 5-FU group, the mRNA and protein expression levels of E-cadherin were up-regulated(P<0.05), while the mRNA and protein expression levels of N-cadherin, Slug and Vimentin were down-regulated in the combined group(P<0.05). Conclusion::YQJPHY has an inhibitory effect on the growth of gastric cancer, and after being combined with 5-FU, it has a good synergistic effect on inhibiting the growth of gastric cancer and decreasing EMT. The mechanism may be related to promoting the conversion from M2-TAMs to M1-TAMs in gastric tumor micro-environment.