Objective To explore the mechanism of the gut-lung axis in paraquat-induced lung injury in mice, with a focus on analyzing the changes in intestinal gene expression and their potential roles. Methods Specific pathogen-free C57BL/6 wild-type mice were randomly divided into control, low-dose, and high-dose groups, with 10 mice in each group. Mice in the three groups received a single intragastric administration of paraquat solution at doses of 0, 25, or 50 mg/kg body weight. The mice were euthanized on day 21. Lung histopathological changes were assessed, and the differentially expressed genes (DEGs) in the intestinal tissues of mice in these two groups were analyzed through transcriptomics. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore potential mechanisms of the gut-lung axis in paraquat-induced lung injury and fibrosis. Results Paraquat exposure induced dose-dependent pulmonary injury and fibrosis in the mice. The Ashcroft score of lung tissue was higher in the mice of low-dose group than that in the control group (P<0.05). Both the lung organ coefficient and Ashcroft score of lung tissues in the mice of high-dose group were higher than those in the control group and the low-dose group (all P<0.05). The result of transcriptomic analysis showed 146 DEGs, including 91 upregulated and 55 downregulated genes, in intestinal tissues of mice in the low-dose group, and 57 DEGs, including 47 upregulated and 10 downregulated genes in the high-dose group, compared with the control group. Notably, 19 DEGs were commonly altered in both low- and high-dose groups. The result of GO enrichment analysis showed that the DEGs were primarily involved in biological processes including "immune response", "oxidative stress" and "cell differentiation". The result of KEGG enrichment analyses showed that DEGs were primarily involved in key processes including "oxidative stress response path way", "immune response path way" and "digestion and absorption path way". Conclusion Paraquat exposure alters intestinal gene expression, particularly in genes in biological processes related to immune responses and oxidative stress. These changes may mediate inflammatory signaling via the gut-lung axis and contribute to the development of paraquat-induced pulmonary fibrosis.

Objective To investigate the effects and mechanisms of silica dust on the apoptosis of alveolar epithelial cell (AEC) through in vitro and animal experiments. Methods i) In vitro experiment. A549 cells were stimulated with 100 mg/L silica suspension for 0, 12, 24 and 48 hours. The cell apoptosis rate was detected by flow cytometry. ii) Animal experiment. Specific pathogen-free male C57BL/6 mice were randomly divided into control, 14-day, 28-day, and 56-day groups, with five mice in each group. The mice in the control group were sacrificed at 56 days after being treated with 40.0 μL 0.9% sodium chloride solution, and the mice in the last three groups were sacrificed at 14, 28 and 56 days after being treated with 40.0 μL silica suspension with a mass concentration of 125 g/L via tracheal exposure method. The lung tissues of mice were collected to measure lung organ coefficients. Masson staining was used to detect the degree of pulmonary fibrosis, and Ashcroft scores were evaluated. The apoptosis of AEC in mice was observed by TUNEL immunofluorescence assay. iii) The mRNA relative expression of apoptosis-related genes in A549 cells and mouse lung tissue was detected using reverse transcription and real-time fluorescence quantitative polymerase chain reaction. Results i) In vitro experiment. The apoptosis rate of A549 cells increased with longer silica exposure (all P<0.05). The relative expression of B cell lymphoma-2 (BCL-2) mRNA in A549 cells in 24 h group and 48 h group decreased (both P<0.05), and the relative expression of BCL-2 associated X protein (BAX) mRNA increased (both P<0.05), compared with 0 h group. The mRNA relative expression of caspase (CASP) -3 and CASP-9 in A549 cells increased with longer silica exposure (all P<0.05). ii) Animal experiment. The lung organ coefficients and Ashcroft score in mice progressively increased (all P<0.05), the degree of pulmonary fibrosis was gradually aggravated, and TUNEL positive cells in lung tissue were gradually increased, while Bax, Casp-3 and Casp-9 mRNA relative expression increased with longer silica exposure (all P<0.05). Conclusion Silica dust may cause pulmonary fibrosis by inducing apoptosis of AEC, with a time-dependent effect. The mechanism may be related to the effect of silica dust on mitochondrial apoptosis through Bcl-2/Bax/Caspase-3 signaling pathway.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.

Objective To evaluate the pharmacokinetics(PK)of tenofovir alafenamide Fumarate tablets(25 mg)in healthy Chinese subjects after single oral administration to provide a basis for bioequivalence evaluation.Methods Using a single-dose,randomized,open-lable,two-period,two-way crossover design under fasting condition,while three-way crossover design under fed condition,42 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test product(T)or reference product(R)25 mg.Plasma concentration of tenofovir alafenamide and tenofovir were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The pharmacokinetic parameters were calculated by WinNonlin software(8.1 version)using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The test product and the reference product under fasting study,the main PK parameters of tenofovir alafenamide were as follows:Cmax were(215.17±94.24)and(199.30±71.11)ng·mL-1;AUC0-t were(135.44±71.60)and(123.91±53.82)h·ng·mL-1;the main PK parameters of tenofovir were as follows:Cmax were(7.30±2.27)and(7.12±1.74)ng·mL-1,AUC0-t of tenofovir were(237.16±47.09)and(230.06±43.41)h·ng·mL-1,respectively.The test product and the reference product under fed study,the main PK parameters of tenofovir were as follows:Cmax were(197.69±82.19)and(197.10±110.54)ng·mL-1;AUC0-t were(197.69±82.19)and(197.10±110.54)h·ng·mL-1;the main PK parameters of tenofovir were as follows:CMax were(2.57±1.37)and(2.58±1.31)ng·mL-1;AUC0-t were(227.08±74.33)and(238.51±128.30)h·ng·mL-1,respectively.The 90％confidence interval for geometric mean ratio of Cmax,AUC0-tof T and R under fed condition were between 80.00％-125.00％,respectively.The incidence of adverse events in fasting and fed tests was 21.43％and 30.95％,respectively,and no serious adverse event was reported.Conclusion The test formulation and reference formulation of tenofovir alafenamide fumarate tablets were equivalent and was safe.

Objective:To summarize the HRCT and MRI appearances of stapical footplate fistula related to inner ear malformation (SFF-Re-IEM).Methods:The HRCT and MRI materials of 48 cases (53 ears) SFF-Re-IEM were retrospectively analyzed. Among them, 25 SFF-Re-IEM ears were confirmed by surgery. Their CT and MRI findings including associated IEM type, internal auditory canal (IAC) malformation, tympanic fluid, its density and signal features, and accompanied labyrinthitis were recorded.Results:Among 48 cases (53 ears) with SFF-Re-IEM, 17 ears with incomplete partition type Ⅰ, accounting for 32.1%, 13 ears with common cavity for 24.5%, 13 ears with cochlear aplasia for 24.5%, 7 ears with cochlear dysplasia Ⅱ for 13.2%, and 3 ears with Mondini for 5.7%,were found respectively. 94.3% of them were associated with a defect or dysplasia in the found of the IAC. They were divided into 4 types according to the intact of the stapical footplate and accompanied CSF otorrhea: 22 ears were diagnosed as the stapical footplate leaking, of them, 2 ears might come from the stapical footplate bony defect, 6 ears were from the stapical footplate hernia. 1 ear belonged to the peristapical footplate leaking. 30 ears with the isolated the stapical footplate hernia were another found. The bony defect in 2 ears with the stapical footplate bony defect were not presented on CT and MRI.The focal bony defect of the affected stapical footplate of 36 ears with the stapical footplate hernia were demonstrated, which presented the hemispherical protruding into the tympana, the soft-tissue density on CT, and CSF-like signal on the MR heaved-T2WI images. Among 22 ears with the stapical footplate leaking, their imaging appearances varied from the different amount of the leaking CSF. Besides the focal bony defects of the affected stapical footplates, there were much more CSF-like density or signal in the ipsilateral tympanic cavity in 17 affected ears connecting with the vestibule through the defect area. In the CSF leaking ears with less CSF leaking in 5 ears, the CSF-like cysts like SFH were shown on the stapical footplate defect area, but their outer edges were irregular, and the CSF-like signal scattering in the tympanic cavity did not connect with the protruding cysts at the stapical area.Conclusion:The variable appearances of the SFF-Re-IEM ears based on the different subtypes are its characteristic HRCT and MRI appearances. This is helpful for the SFF-Re-IEM diagnosing to grasp its imaging features.

Abstract： Objective　To investigate and analyze the factors influencing the direct medical costs of tuberculosis patients in Hainan Province, so as to provide scientific reference for reducing the medical burden of patients and adjusting the medical insurance reimbursement policies in the local area. Methods　Using the total health expenditure accounting data of Hainan Province in 2020, including the outpatient and inpatient data of 14 provincial medical institutions, 235 city and county level medical institutions, and other relevant data from the 2020 Hainan Statistical Yearbook and Health Financial Yearbook, the direct medical costs of tuberculosis patients in the province in that year were calculated, and the influencing factors were explored using single factor analysis and multivariate generalized linear model. Results　The final number of cases included in this study was 11 979, including 7 526 males (62.83%) and 4 453 females (37.17%). The total direct medical costs of patients were 43.207 3 million yuan, of which the total outpatient costs were 2.733 9 million yuan (6.32%) and the total inpatient costs were 40.473 4 million yuan (93.67%). In the cost composition analysis, the drug cost was 17.971 million yuan (41.44%), the examination cost was 8.854 7 million yuan (20.49%), other costs were 16.445 5 million yuan (38.06%), and the median (quartile) M(P25,P75) direct medical cost of each patient was 177.50 (66.73,764.89) yuan. The multivariate generalized linear model analysis showed that hospitalization, new rural cooperative medical insurance (NRCMI) and urban employee medical insurance were the influencing factors of the increase in direct medical costs of tuberculosis patients the median (quartile) M(P25,P75) of direct medical costs are 10 425.04 (6 560.87,17 374.9), 10 246.5 (5 871.28,17 220.33), 3 177.2 (293.09,7 730.23) yuan respectively; the OR(95%CI) values were -3.505 (-3.499- -3.517), 1.559 (1.551-1.569) and 2.191 (2.188-2.207) respectively. Conclusions　The direct medical costs of tuberculosis patients in Hainan Province are high. Hospitalization, the new rural cooperative medical insurance and the medical insurance for urban workers are the influencing factors of the increase in costs.

Occupational exposure to diacetyl can lead to bronchiolitis obliterans. In this paper, two patients with severe obstructive ventilation disorder who were exposed to diacetyl at a fragrance and flavours factory were analyzed. The clinical manifestations were cough and shortness of breath. One of them showed Mosaic shadows and uneven perfusion in both lungs on CT, while the other was normal. Field investigation found that 4 of the 8 workers in the factory were found to have obstructive ventilation disorder, and 2 had small airway dysfunction. This paper summarizes the diagnostic process of patients in order to improve the understanding of airway dysfunction caused by occupational exposure to diacetyl and promote the development of relevant standards.
Humans ; Diacetyl/adverse effects* ; Occupational Diseases/diagnosis* ; Occupational Exposure/adverse effects* ; Lung ; Bronchiolitis Obliterans/diagnosis*

OBJECTIVE: To assess the efficacy and safety of Guanxin Danshen Dripping Pills (GXDS) in the treatment of depression or anxiety in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). METHODS: From September 2017 to June 2019, 200 CHD patients after PCI with depression and anxiety were included and randomly divided into GXDS (100 cases) and placebo control groups (100 cases) by block randomization and a random number table. Patients in the GXDS and control groups were given GXDS and placebo, respectively, 0.4 g each time, 3 times daily for 12 weeks. The primary outcomes were scores of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Scale (GAD-7) and the Seattle Angina Pectoris Scale (SAQ). The secondary outcomes included 12 Health Survey Summary Form (SF-12) scores and the first onset time and incidence of major adverse cardiovascular events (MACEs). Other indices including blood pressure, blood lipids, microcirculation and inflammatory-related indices, etc. were monitored at baseline, week 4, and week 12. RESULTS: In the full analysis set (200 cases), after treatment, the PHQ-9 and GAD-7 scores in the GXDS group were considerably lower than those in the control group (P<0.05). Compared with the baseline, the total PHQ-9 scores of the experimental and control groups decreased by 3.97 and 1.18, respectively. The corrected mean difference between the two groups was -2.78 (95% CI: -3.47, -2.10; P<0.001). The total GAD-7 score in the GXDS group decreased by 3.48% compared with the baseline level, while that of the placebo group decreased by 1.13%. The corrected mean difference between the two groups was -2.35 (95% CI: -2.95, -1.76; P<0.001). The degree of improvement in SAQ score, SF-12 score, endothelin and high-sensitive C-reactive protein levels in the GXDS group were substantially superior than those in the placebo group, and the differences between the two groups were statistically significant (P<0.05). Similar results were obtained in the per protocol population analysis of 177 patients. Three cases of MACES were reported in this study (1 in the GXDS group and 2 in the placebo group), and no serious adverse events occurred. CONCLUSIONS GXDS can significantly alleviate depression and anxiety, relieve symptoms of angina, and improve quality of life in patients with CHD after PCI. (Registration No. ChiCTR1800014291).
Humans ; Percutaneous Coronary Intervention/adverse effects* ; Quality of Life ; Depression ; Coronary Disease/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Angina Pectoris/drug therapy* ; Prognosis ; Anxiety ; Treatment Outcome ; Double-Blind Method

OBJECTIVES: To explore the effects of somatostatin on the levels of gastrointestinal hormones and clinical outcomes in critically ill infants after gastrointestinal surgery. METHODS: Using a random number table method, critically ill infants after gastrointestinal surgery who were admitted to the Intensive Care Unit of Xuzhou Children's Hospital from June 2019 to June 2021 were randomly divided into an observation group (29 cases) and a control group (30 cases). The control group received routine treatment such as anti-infection and hemostasis after surgery, while the observation group received somatostatin in addition to the routine treatment [3.5 μg/(kg·h) infusion for 7 days]. The levels of serum gastrin (GAS), motilin (MTL), insulin, and glucagon-like peptide-1 (GLP-1) before surgery, on the 3rd day after surgery, and on the 7th day after surgery were compared between the two groups. The recovery progress and incidence of complications after surgery were also compared between the two groups. RESULTS: There was no significant difference in the levels of serum GAS, MTL, insulin, and GLP-1 between the two groups before surgery (P>0.05). On the 3rd and 7th day after surgery, the levels of serum GAS, MTL, insulin, and GLP-1 in the observation group were higher than those in the control group (P<0.05). In the observation group, the levels of GAS, MTL, insulin, and GLP-1 on the 7th day after surgery were higher than those before surgery and on the 3rd day after surgery (P<0.05), and the levels on the 3rd day after surgery were higher than those before surgery (P<0.05). There was no significant difference in the levels of serum GAS, MTL, and insulin before surgery, on the 3rd day after surgery, and on the 7th day after surgery in the control group (P>0.05). The level of GLP-1 on the 7th day after surgery was higher than that before surgery and on the 3rd day after surgery (P<0.05), and the level on the 3rd day after surgery was higher than that before surgery (P<0.05) in the control group. The observation group had shorter first time of anal exhaust, recovery time of bowel sounds, and first time of defecation after surgery compared to the control group (P<0.05). The incidence of complications after surgery in the observation group was lower than that in the control group (10% vs 33%, P<0.05). CONCLUSIONS Somatostatin can increase the levels of serum GAS, MTL, insulin, and GLP-1 in critically ill infants after gastrointestinal surgery, promote the recovery of gastrointestinal function, and reduce the incidence of postoperative complications.
Humans ; Infant ; Critical Illness ; Digestive System Surgical Procedures ; Glucagon-Like Peptide 1 ; Insulin ; Prospective Studies ; Somatostatin/therapeutic use*

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*