OBJECTIVES: Acute lung injury (ALI) is an acute respiratory failure syndrome characterized by impaired gas exchange. Due to the lack of effective targeted drugs, it is associated with high mortality and poor prognosis. Tripterygium wilfordii (TW) has demonstrated anti-inflammatory activity in the treatment of various diseases. This study aims to investigate the effects and underlying mechanisms of TW on myeloid-derived suppressor cells (MDSCs) in ALI, providing experimental evidence for TW as a potential adjuvant therapy for ALI. METHODS: Eighteen specific pathogen-free (SPF) C57BL/6 mice were randomly divided into normal control (NC; intranasal saline), lipopolysaccharide (LPS; 5 mg/kg intranasally to induce ALI), and LPS+TW (50 mg/kg TW by gavage on the first day of modeling, followed by 5 mg/kg LPS intranasally to induce ALI) groups (n=6 each). Lung injury and edema were assessed by histopathological scoring and wet-to-dry weight ratio. Cytokine levels [interleukin (IL)-1β, IL-6, IL-18, tumor necrosis factor-α (TNF-α)] in lung tissue lavage fluid were measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to assess the proportions of MDSCs, polymorphonuclear MDSCs (PMN-MDSCs), and monocytic MDSCs (M-MDSCs) in bone marrow, spleen, peripheral blood, and lung tissue, as well as reactive oxygen species (ROS) levels in lung tissues. Messenger RNA (mRNA) expression levels of inducible nitric oxide synthase (iNOS) and arginase-1 (ARG-1) in lung tissues were determined by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). PMN-MDSCs sorted from the lungs of LPS-treated mice were co-cultured with splenic CD3⁺ T cells and divided into NC, triptolide (TPL)-L, and TPL-H groups, with bovine serum albumin, 25 nmol/L TPL, and 50 nmol/L TPL, respectively. Flow cytometry was used to detect the effect of PMN-MDSCs on T-cell proliferation, and RT-qPCR was used to measure iNOS and ARG-1 mRNA expression. RESULTS: Compared with the NC group, the LPS group showed marked lung pathology with significantly increased histopathological scores and wet-to-dry ratios (both P<0.001). TW treatment significantly alleviated lung injury and reduced both indices compared with the LPS group (both P<0.05). Cytokine levels were significantly decreased in the LPS+TW group compared with the LPS group (all P<0.001). The proportions of MDSCs in CD45⁺ cells from spleen, bone marrow, peripheral blood, and lung, as well as PMN-MDSCs from spleen, peripheral blood, and lung, were significantly reduced in the LPS+TW group compared with the LPS group (all P<0.05), accompanied by reduced ROS levels in lung tissues (P<0.001). iNOS and ARG-1 mRNA expression in lung tissues was significantly lower in the LPS+TW group than in the LPS group (both P<0.001). In vitro, compared with the TPL-L group, the TPL-H group showed significantly increased CD3⁺ T-cell proliferation (P<0.001), and decreased iNOS and ARG-1 mRNA expression (all P<0.05). CONCLUSIONS TW alleviates the progression of LPS-induced ALI in mice, potentially by reducing the proportion of MDSCs in lung tissues and attenuating the immunosuppressive function of PMN-MDSCs.
Animals ; Acute Lung Injury/chemically induced* ; Myeloid-Derived Suppressor Cells/cytology* ; Tripterygium/chemistry* ; Mice, Inbred C57BL ; Mice ; Cell Differentiation/drug effects* ; Male ; Lipopolysaccharides ; Nitric Oxide Synthase Type II/genetics* ; Cytokines/metabolism* ; Reactive Oxygen Species/metabolism* ; Diterpenes/pharmacology* ; Epoxy Compounds ; Phenanthrenes

Objective To investigate the epidemiological characteristics and trends in the prevalence of tuberculosis among in the six urban districts of Tianjin from 2014 to 2023, so as to provide scientific basis for the prevention and control of tuberculosis. Methods Data on the occurrence of new tuberculosis cases among in the six urban districts of Tianjin from 2014 to 2023 were collected through the Tianjin Infectious Disease Report Information Management System, and the epidemiological characteristics of new tuberculosis cases were descriptively analyzed. Then the Average Annual Percentage Change (AAPC) statistics were used to characterize the magnitude and direction of trends. Results A total of 17 818 tuberculosis cases were reported in the six urban districts of Tianjin from 2014 to 2023 , with an average annual reported prevalence rate of 25.61/100 000. The prevalence rate of tuberculosis in the six urban districts of Tianjin from 2014 to 2023 showed a decreasing trend, reporting a prevalence rate of 35.47/100 000 in 2014 and 22.72/100 000 in 2023, and AAPC is -4.86% (-7.13% to -1.56%) , with statistical difference (P<0.05). In terms of gender, the overall prevalence rate of tuberculosis was 31.17/100,000 in males and 19.47/100,000 in females, with statistical difference (χ²=276.12 , P<0.05). The incidence in people younger than 25 years and older than 55 years is on the rise from 2014 to 2023. In terms of occupation, household duties, unemployed people, retired people and office clerks showed a high prevalence rate of tuberculosis. Conclusion The overall prevalence of adult tuberculosis in the six urban districts of Tianjin from 2014 to 2023 shows a decreasing trend, whereas the prevalence rate of males is higher than that of females, and the elderly, families, unemployed people, retirees and office clerks are high-risk groups, so targeted preventive and control measures, health education and screening should be strengthened.

BACKGROUND:Diabetic nephropathy is an important cause of end-stage renal disease,and intestinal barrier damage plays an important role in the occurrence and development of diabetic nephropathy. OBJECTIVE:To observe the protective effect of human umbilical cord mesenchymal stem cells on the intestinal barrier in rats with diabetic nephropathy. METHODS:Thirty 8-week-old male SD rats were randomly assigned to healthy control group,model group and human umbilical cord mesenchymal stem cell group,with 10 rats in each group.Rats in the human umbilical cord mesenchymal stem cell group were injected with 1×106 human umbilical cord mesenchymal stem cells through the tail vein once a week for 4 weeks after the model establishment of diabetic nephropathy.Rats in the healthy control group and the model group were injected with an equal volume of PBS at the same time.1 week after the last injection,the histomorphological changes in the kidney and colon were observed under a light microscope.The expressions of ZO-1 and Occludin in the colon tissue of rats were detected by immunohistochemistry.Serum D-lactic acid and lipopolysaccharide levels were detected by ELISA.In addition,the distribution of human umbilical cord mesenchymal stem cells labeled with DiR dye in rats was observed by in vivo imaging system.The expression of human mesenchymal stem cell surface marker antigens CD44 and CD90 in colon tissue was detected by immunohistochemistry. RESULTS AND CONCLUSION:(1)Compared with the model group,human umbilical cord mesenchymal stem cell transplantation significantly inhibited the increase of urea nitrogen,serum creatinine,24-hour urine protein level and urinary albumin/creatinine ratio in diabetic nephropathy rats(all P<0.05).(2)The expression of human mesenchymal stem cell surface markers CD44 and CD90 was found in the colon of diabetic nephropathy rats.(3)Compared with the healthy control group,the expression levels of tight junction proteins Occludin and ZO-1 in the colon tissue of the model group were significantly reduced,while the expressions of Occludin and ZO-1 were significantly increased after treatment with human umbilical cord mesenchymal stem cells.(4)Compared with the model group,human umbilical cord mesenchymal stem cell transplantation significantly reduced serum D-lactic acid and lipopolysaccharide levels in diabetic nephropathy rats.(5)The results suggest that human umbilical cord mesenchymal stem cells may protect the intestinal barrier function by enhancing the expression of intestinal tight junction proteins in diabetic nephropathy rats.

Objective:To observe the clinical efficacy of intermittent feeding through an oral to esophageal (IOE) tube for persons with a late-onset swallowing disorder after radiotherapy for nasopharyngeal carcinoma.Methods:Fifty-six patients with late-onset swallowing difficulties after radiotherapy for nasopharyngeal carcinoma were divided at random into an observation group and a control group, each of 28. In addition to conventional therapy, the controls were fed through an indwelling nasogastric tube (NGT) while an IOE tube was used in the observation group. The nutritional status of the two groups was compared after 20 hours and after 15 days of treatment. Depression, oral feeding ability, leakage and aspiration, and life quality were evaluated using patient health questionnaire-9 (PHQ-9), a functional oral feeding scale (FOIS), a leakage-aspiration scale (PAS), and a swallowing-quality of life (SWAL-QOL) evaluation. From the 3rd day after admission the daily amount fed was recorded.Results:At admission there were no significant differences between the two groups. After 15 days, however, there was significantly greater improvement observed in the average serum albumin, hemoglobin, serum total protein, serum prealbumin level, body mass index(BMI) and SWAL-QOL score of the experimental group compared to the control group, with significantly fewer members suffering from depression. From the 4th day after admission the observation group′s members ate a significantly larger proportion of the target feeding amount.Conclusion:IOE feeding can improve the nutritional status, psychological status, and life quality of persons with a late-onset swallowing disorder more effectively than NGT feeding, with a lower incidence of adverse events.

OBJECTIVE To compare the similarities and differences of the two methods in analyzing the use of opioids in third grade class A medical institutions and provide a reference for the management of opioids in medical institutions. METHODS Two methods， Defined Daily Dose （DDD） and Oral Morphine Equivalent （OME）， were used to count the opioid prescription data of five comprehensive medical institutions of third grade class A （named H1-H5） in Shanxi province in 2020， calculate consumption sum of opioid， annual per capita consumption sum， patient cost burden and drug consumption sum ratio， compare the index results presented by the two analysis methods， and explore the application scenarios of the advantages of each of the two evaluation methods. RESULTS The ranking of consumption sum of opioid and patient cost burden calculated by the two methods was the same in the five sample medical institutions， but the ranking of per capita consumption sum was different. Taking the 5 medical institutions as a whole， the top 4 rankings of consumption sum ratio for each species of opioid compared by both methods were the same， i. e. remifentanil＞sufentanil＞oxycodone＞morphine. The ratio of remifentanil was close to 50%. When comparing the ranking of consumption sum ratio in each medical institution， the ranking calculated by the two methods was different for those medical institutions except for H1 medical institutions. The consumption sum ratio of fentanyl calculated by DDD method was significantly higher than that of OME method； whereas consumption sum ratio of remifentanil calculated by OME method was significantly higher than that of DDD method. Perioperative patients had the highest consumption sum ratio， about 50%. The consumption sum ratio of critically ill patients in H3 jwsydey@163.com medical institutions and inpatient patients with cancer pain and other patients in H5 medical institutions calculated by DDD method was significantly higher than that by OME method. There were differences in the order of cost burden of different types of patients calculated by two methods. CONCLUSIONS DDD method can accurately reflect the dosage of opioid drugs and facilitate the monitoring and management of the dosage； OME method can more reflect the analgesic effect and compare the cost burden of patients.

OBJECTIVE: To evaluate the prospective association between cumulative resting heart rate (cumRHR) and rapid renal function decline (RRFD) in a cohort of individuals aged 60 and older. METHODS: In the Tianjin Chronic Kidney Disease Cohort Study, the individuals who underwent three consecutive physical examinations between 2014 and 2017, with estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m² and aged 60 years or older were enrolled. A total of 27,564 patients were prospectively followed up from January 1, 2017 to December 31, 2020. The 3-year cumRHR was calculated. The primary outcome was RRFD, defined as an annualized decline in eGFR of 5 mL/min per 1.73 m² or greater. Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders. RESULTS: During a median follow-up of 3.2 years, a total of 4,347 (15.77%) subjects developed RRFD. In fully-adjusted models, compared with the lowest quartile of cumRHR, the odds ratio (OR) for the highest was 1.44 (1.28-1.61), P < 0.001. Furthermore, each 1-standard deviation (27.97 beats/min per year) increment in cumRHR was associated with a 17% (P < 0.001) increased risk of RRFD, with a linear positive correlation (P for non-linear = 0.803). Participants with a 3-year cumRHR ≥ 207 (beats/min) * year (equivalent to ≥ 69 beats/min per year in 3 years) were found to be at a higher risk of RRFD. CONCLUSIONS The cumRHR is significantly associated with a higher risk of RRFD among older adults. These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Animals ; Mice ; Microscopy ; Seizures ; Brain

OBJECTIVE: To investigate the clinical features and prognosis of acute myeloid leukemia (AML) patients with the mixed lineage leukemia (MLL) gene rearrangements AF6 (MLL-AF6) positive. METHODS: In the study, 11 patients who were newly diagnosed with MLL-AF6 positive AML were analyzed retrospectively, related literature was reviewed to clarify the clinical features and prognosis of MLL-AF6 positive patients. RESULTS: Among the 11 patients, there were 6 males and 5 females, with a median age of 36 years. Six patients were diagnosed with AML M5 and five with M4 according to FAB classification (French-American-British classification systems). Gingival swelling and pain occurred in 6 cases and fever occurred in 5 cases. At first diagnosis, the median white blood cells were 55.5×10⁹/L. Immunotype showed the expression of myeloid/monocyte and early stem cell series antigens. The expression level of MLL-AF6 fusion gene (real-time quantitative PCR) was 14.2%-214.5%, and 6/11 cases (54.5%) were associated with high EVI1 gene expression. Mutations of KRAS, TET2, ASXL1, TP53, DNMT3A, and FLT3-ITD were detected by next generation sequencing (NGS) in 4 patients. Chromosome G banding examination showed that 2 cases were t(6;11)(q27, q23) with complex karyotype abnormality, 4 cases with +8 abnormality and 2 cases with normal karyotype. Hematological complete remission (CR) was achieved in 8/11 patients (72.7%) after conventional induction chemotherapy, and primary drug resistance was observed in 3 patients. Two of the eight patients with CR were negative for minimal residual disease (MRD), with a median CR duration of 4.5 months. Two patients with positive MRD and three patients with refractory recurrence underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), but all died due to leukemia progression. At the end of follow-up on December 1, 2019, 2 patients were alive and 9 died, with median survival time of 9 months. CONCLUSION The AML patients with MLL-AF6 positive were mostly young, the majority of FAB types were M4 and M5, and most of the patients often had fever as the first symptom, with increased white blood cells, accompanied by organ infiltration, and high EVI1 gene expression. The hematological remission rate of routine chemotherapy is not low, but it is difficult to achieve molecular remission, most of which have early recurrence. Early allo-HSCT in a molecular negative state may prolong the CR duration.
Adult ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Male ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Oncogene Proteins, Fusion/genetics* ; Prognosis ; Remission Induction ; Retrospective Studies