OBJECTIVE To analyze the influencing factors of voriconazole trough concentration and adverse drug reactions （ADR） in renal transplant recipients. METHODS Data from inpatients who received voriconazole and therapeutic drug monitoring in our hospital between January 2022 and August 2023 were retrospectively analyzed. Patients were divided into renal transplant group and non-renal transplant group based on transplantation status. A 1∶1 propensity score matching （PSM） method was used to balance differences in baselines between the two groups. Voriconazole trough concentrations， target attainment rate， clinical efficacy， and ADR were compared between the two groups. Multiple linear regression （backward） was used to analyze the factors influencing voriconazole trough concentrations in the renal transplant group. Univariate analysis and binary Logistic regression were used to identify independent risk factors for ADR in the renal transplant group. RESULTS After PSM， 48 patients were included in each group. There were no statistically significant differences in the mean voriconazole trough concentration， target attainment rate or efficacy rate between the two groups （P＞0.05）. The total incidence of ADR was significantly higher in the renal transplant group than in the non-renal transplant group （P＜0.05）. Multiple linear regression analysis showed that age， average daily dose， pulmonary infection， total bilirubin during medication， day-1 loading dose， use of the original drug， concomitant immunosuppressant use， and the occurrence of ADR were factors influencing voriconazole trough concentration in renal transplant patients （P＜0.05）. Binary Logistic regression analysis showed that abnormal direct bilirubin during medication [OR＝7.747， 95%CI （1.334， 45.005）， P＝0.023] was an independent risk factor for ADR in renal transplant patients receiving voriconazole. CONCLUSIONS Age， average daily dose， pulmonary infection， use of the original drug， day-1 loading dose， total bilirubin during medication， concomitant immunosuppressant use， and the occurrence of ADR are the factors influencing voriconazole trough concentration in renal transplant patients. Furthermore， patients with abnormal direct bilirubin during medication are more susceptible to ADR.

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome (MDS) with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50% (MDS-E) .Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1 436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1 436 newly diagnosed patients with complete data were included in the study, of which 337 (23.5%) patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50% (MDS-NE) (all P<0.05). The proportion of MDS cases with ring sideroblasts (MDS-RS) was higher in the MDS-E group than in the MDS-NE group, and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group (all P<0.05). Among patients with MDS-RS, the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group (0 vs 11.9%, P=0.048 and 2.4% vs 15.1%, P=0.053, respectively). Among patients with TP53 mutations, the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group (87.5% vs 64.6%, P=0.003 and 84.0% vs 54.2%, P<0.001, respectively). Survival analysis of patients with MDS-RS found that the overall survival (OS) in the MDS-E group was better than that in the MDS-NE group [not reached vs 63 (95% CI 53.3-72.7) months, P=0.029]. Among patients with TP53 mutations and excess blasts, the OS in the MDS-E group was worse than that in the MDS-NE group [6 (95% CI 2.2-9.8) months vs 12 (95% CI 8.9-15.1) months, P=0.022]. Multivariate analysis showed that age of ≥65 years ( HR=2.47, 95% CI 1.43-4.26, P=0.001), mean corpuscular volume (MCV) of ≤100 fl ( HR=2.62, 95% CI 1.54-4.47, P<0.001), and TP53 mutation ( HR=2.31, 95% CI 1.29-4.12, P=0.005) were poor prognostic factors independent of the Revised International Prognostic Scoring System (IPSS-R) prognosis stratification in patients with MDS-E. Conclusion:Among patients with MDS-RS, MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations, and the OS in the MDS-E group was longer than that in the MDS-NE group. Among patients with TP53 mutations, MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations, and among TP53-mutated patients with excess blasts, the OS in the MDS-E group was shorter than that in the MDS-NE group. Age of ≥65 years, MCV of ≤100 fl, and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.

Objective:To investigate the mechanism of Hongteng Decoction in inhibiting the adenomyosis (ADS) fibrosis by observing the effects on the key proteins of epithelial mesenchymal transformation (EMT), fibroblast-to-myofibroblast transformation (FMT) and Hippo pathway in uterine tissue of mice with ADS.Methods:ICR mice were divided into blank group, model group, Hongteng Decoction group, and verteporfin group according to random number table method, with 8 mice in each group. The day of birth of the mice was day 0, and from day 1, mice in model group, Hongteng Decoction group and verteporfin group were given 1 mg/kg tamoxifen solvent for gavage for 5 days. On the 42nd day after molding, HE staining verified that the molding was successful. Starting from the 43rd day, mice in the Hongteng Decoction group were given TCM solution of Hongteng Decoction 16.5 g/kg everyday, and intraperitoneally injected with 0.9%NaCl solution (100 μl/10 g) every 3 days. Mice in the verteporfin group were intraperitoneally injected with verteporfin solution of 100 mg/kg every 3 days, and intragastric with water of 100 μl/10 g everyday. Mice in blank group and model group were intragastric with constant volume of water daily and intraperitoneally injected with 0.9%NaCl solution every 3 days. The drugs were administered for 60 days. The fibrosis degree of mice in each group was evaluated by Masson staining. The expressions of E-cadherin, Vimentin, α-SMA, YAP and Snail in uterine tissue of mice in each group were detected by immunohistochemistry and Western blot.Results:Compared with the model group, the Masson staining expression in Hongteng Decoction group significantly decreased ( P<0.05). Immunohistochemical and Western blot analysis showed that the expression of E-cadherin in uterine tissue of mice in Hongteng Decoction group significantly increased ( P<0.05), while the expressions of Vimentin, α-SMA and YAP significantly decreased ( P<0.01, P<0.05) compared with the model group. Conclusion:Hongteng Decoction can inhibit the occurrence of EMT and FMT in ADS, thereby inhibiting fibrosis, and its mechanism is related to the regulation of Hipoo/YAP pathway.

Talents are the core driving force to promote the high-quality development of public hospitals,and the talent team building is an important factor for hospitals to get sustainable development and improve comprehensive competitiveness.In view of the shortage of high-level talents,the imperfect talent reserve system,and the lagging personnel management mechanism of public hospitals and the resulting unreasonable talent team structure and talent gap,public hospitals should take talent team building as the starting point,pay equal attention to the introduction and training of talents,interact with discipline construction and talent construction,vigorously promote the construction of personnel management system and mechanism innovation,form a standardized,scientific,refined and efficient modern hospital management system,so that the effectiveness of talents can be max-imized,and provide intellectual support for the high-quality development of public hospitals.

Objective:To investigate the etiology, clinical manifestations, clinicopathological features of cystic neutrophil granulomatous mastitis (CNGM).Methods:From Jan 2019 to Dec 2020, 95 CNGM cases diagnosed by biopsy pathology at Chongqing Hospital of Traditional Chinese Medicine and Chongqing Liangping District Hospitol of Traditional Chinese Medicine were reviewed.Results:There were 95 female patients, aged 21 to 50 years, with a median age of 32 years. Laboratory examination showed that 56% (53/95) cases had elevated rheumatoid antibody level, 27 % (26/95) had increased level of serum thyroid antibody, 15% (14/95) had elevated antineutrophil antibody, 35% (33/95) had increased ESR, 38% (36/95) had increased C-reactive protein. The positive rate of Gram-stained bacilli was 82% (78/95). Histology: pyogenic granuloma with lobule of breast as the center, the center of granuloma was cystic vacuole.Immunohistochemistry showed that the inflammatory cells in and around granuloma were mainly CD3 + cells, and CD4 + cells were more than CD8 + cells. Conclusions:The cystic neutrophilie granulo matous mastitis is a rare type of idiopathic granulomatous mastitis. The diagnosis of CNGM is dependent on its specific pathological features.

Ischemic stroke is a major public health problem worldwide. Although the circadian clock is involved in the process of ischemic stroke, the exact mechanism of the circadian clock in regulating angiogenesis after cerebral infarction remains unclear. In the present study, we determined that environmental circadian disruption (ECD) increased the stroke severity and impaired angiogenesis in the rat middle cerebral artery occlusion model, by measuring the infarct volume, neurological tests, and angiogenesis-related protein. We further report that Bmal1 plays an irreplaceable role in angiogenesis. Overexpression of Bmal1 promoted tube-forming, migration, and wound healing, and upregulated the vascular endothelial growth factor (VEGF) and Notch pathway protein levels. This promoting effect was reversed by the Notch pathway inhibitor DAPT, according to the results of angiogenesis capacity and VEGF pathway protein level. In conclusion, our study reveals the intervention of ECD in angiogenesis in ischemic stroke and further identifies the exact mechanism by which Bmal1 regulates angiogenesis through the VEGF-Notch1 pathway.
Rats ; Animals ; Vascular Endothelial Growth Factor A/pharmacology* ; Brain Ischemia/metabolism* ; Ischemic Stroke ; Signal Transduction ; ARNTL Transcription Factors/pharmacology* ; Neovascularization, Physiologic/physiology*

Objective:To explore the predictive value of serum adiponectin (APN) in parenteral nutrition associated cholestasis (PNAC) in premature infants.Methods:A retrospective analysis was conducted on the clinical data of 85 premature infants treated with PN (parenteral nutrition) at the Yiyang Central Hospital from January to December 2021. According to whether PNAC occurred during hospitalization, the infants were divided into 34 PNAC group and 51 non PNAC group. A comparison was made between the PNAC group and the non PNAC group. The serum APN levels in children of different gestational ages in the PNAC group were analyzed, and the risk factors for PNAC in premature infants were analyzed. The predictive value of serum APN in premature PNAC was analyzed.Results:The serum APN levels in the PNAC group were lower than those in the non PNAC group at weeks 1, 3, and 5, and the difference was statistically significant (all P<0.01). The serum APN levels in children with gestational age<34 weeks in the PNAC group were lower than those in children with gestational age≥34 weeks at 1, 3, and 5 weeks, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that gestational age, birth weight, sepsis, fasting time, duration of PN, accumulation of fat emulsion, initial amount of amino acids, and accumulation of amino acids were all risk factors for PNAC in premature infants (all P<0.05). The area under the curve (AUC) of serum APN for predicting PNAC in premature infants was 0.814(95% CI: 0.722-0.906), with a sensitivity of 0.69, specificity of 0.88, and a cutoff value of 13.28 mg/L. Conclusions:Serum APN has a high predictive value for the occurrence of PNAC in premature infants, and should be closely monitored in clinical practice.

Objective:To investigate clinical efficacy of tunneled subcutaneous pedicle flaps in the repair of ipsilateral nasal alar defects.Methods:A total of 20 patients with nasal alar defects after excision of basal cell carcinoma, which were repaired with ipsilateral tunneled subcutaneous pedicle flaps, were retrospectively collected from January 2018 to January 2020. There were 11 male patients and 9 female patients, with an average age of 60.6 years (range, 48 - 76 years) . According to clinical manifestations, the basal cell carcinoma lesions could be classified into 3 types: nodular-ulcerative type (13 cases) , superficial type (4 cases) and pigmented type (3 cases) , and the skin lesions varied from 0.4 cm × 0.5 cm to 0.9 cm × 1.1 cm in size. All the patients received extended surgical resection of basal cell carcinoma, and nasal alar defects were repaired with tunneled subcutaneous pedicle flaps, with the size of flaps ranging from 0.7 cm × 0.8 cm to 1.2 cm × 1.4 cm.Results:All flaps survived successfully, the nasal alar defects were completely repaired, and all wounds healed primarily. During the postoperative follow-up of 6 - 24 months, neither recurrence of tumors nor obvious scar hyperplasia occurred on the nasal ala, and nasal morphology and appearance were favorable.Conclusion:The tunneled subcutaneous pedicle flap can be used for the repair of ipsilateral nasal alar defects following excision of tumors or other lesions, resulting in favorable therapeutic outcomes and aesthetic appearance.