Objective To investigate the identification of staphylococcus aureus lineage ST59 using the combined detection of delta hemolysin allelic variant G10S(HldG10S) and beta hemolysin(β-toxin). Methods Perspective study.A total of 82 non-duplicate clinical staphylococcus aureus were collected from November 2017 to April 2018 in the department of Clinical laboratory, the Third Xiangya Hospital of Central South University, China.The strains were routinely identified by MALDI-TOF MS and the mass spectra were obtained. According to the m/z expression intensity of delta hemolysin(Hld), all strains were divided into three groups:HldG10S (3036±2.0)m/z, Hld (3006±2.0)m/z and ND [no (3036±2.0)m/z and no (3006±2.0)m/z]. The distribution of ST59 in the three groups was detected by MLST. Reverse synergic hemolysis test was used to determine theβ-toxin phenotype. And the sensitivity, specificity and accuracy of HldG10S,β-toxin and the combined detection of HldG10S and Hld to identify ST59 were compared. Results Among the 82 strains, 21 strains expressed HldG10S toxin, accounting for 25.6％. 39 strains expressed Hld toxin, accounting for 47.6％.22 strains did not express HldG10S and Hld toxin, accounting for 26.8％. In HldG10S group,16 strains were ST59, accounting for 76.19％(16/21).ST59 was not found in both Hld and ND groups. All 16 strains of ST59 in HldG10S group producedβ-toxin, while none of the 5 strains of non-ST59 producedβ-toxin. The specificity(100％) and accuracy(100％) of the combined detection was significantly higher than that of HldG10S andβ-toxin single detection of specificity(92.4％, 77.3％) and accuracy(80.5％, 81.7％) (χ2=19.472, P<0.001;χ2=17.792, P<0.001). Conclusion The combined detection of HldG10S andβ-toxin can preliminarily and rapidly identify ST59, which can assist the routine monitoring of the change trend of staphylococcus aureus epidemic.

OBJECTIVEPsoriasis is an autoimmune-related chronic inflammatory skin disease strongly associated with the dysfunction of Th17 cells. Retinoic acid-related orphan nuclear receptor γt (RORγt) plays a critical role in the differentiation and maturation of Th17 cells and in cell-derived immunologic derangement. We conducted this study to investigate potential mechanism by which the derivative of digoxin selectively antagonizes RORγt transcriptional activity.

METHODUsing molecular docking in combination with molecular electrostatic potential (MEP), we detected the interaction between the derivative of digoxin (Dhd) and ROR transcription factor (RORα,RORβ and RORγt), and the results were further confirmed by bioluminescent assay.

RESULTMolecular docking demonstrated that Dhd could exclusively inhibit the conformation of RORγt; bioluminescent assay further indicated that RORγt was selectively antagonized by Dhd in a dose- and time-dependent manner.

CONCLUSIONDhd can selectively suppress RORγt transcriptional activity.

Digoxin ; analogs & derivatives ; pharmacology ; Humans ; Models, Chemical ; Molecular Docking Simulation ; Nuclear Receptor Subfamily 1, Group F, Member 1 ; antagonists & inhibitors ; genetics ; Transcription, Genetic

Objetive Psoriasis is an autoimmune-related chronic inflammatory skin disease strongly associated with the dysfunction of Th17 cells. Retinoic acid-related orphan nuclear receptorγt (RORγt) plays a critical role in the differentiation and maturation of Th17 cells and in cell-derived immunologic derangement. We conducted this study to investigate potential mechanism by which the derivative of digoxin selectively antagonizes RORγt transcriptional activity. Method Using molecular docking in combination with molecular electrostatic potential (MEP), we detected the interaction between the derivative of digoxin (Dhd) and ROR transcription factor (RORα,RORβ and RORγt), and the results were further confirmed by bioluminescent assay. Result Molecular docking demonstrated that Dhd could exclusively inhibit the conformation of RORγt;bioluminescent assay further indicated that RORγt was selectively antagonized by Dhd in a dose- and time-dependent manner. Conclusion Dhd can selectively suppress RORγt transcriptional activity.

This article mainly elaborated the acupuncture and moxibustion treatment scheme of"eighteen needles for reproduction"based on Professor You Zhaoling's reproductive axis theory of"heart-kidney-Chong Ren-uterus".The"eighteen needles for reproduction"aims to regulate the disordered reproductive axis in gynecological reproductive diseases.It selects the acupoints on the main viscera and meridians of the reproductive axis as the main acupoints,and the acupoints regulating the qi and blood of the related viscera as the matching acupoints.Through specific manipulation,it can regulate the qi and blood,dredge the meridians,and treat the viscera,so as to nourish the essence and help pregnancy,and provide ideas and reference for the treatment of gynecological reproductive diseases with acupuncture and moxibustion.

Objetive Psoriasis is an autoimmune-related chronic inflammatory skin disease strongly associated with the dysfunction of Th17 cells. Retinoic acid-related orphan nuclear receptorγt (RORγt) plays a critical role in the differentiation and maturation of Th17 cells and in cell-derived immunologic derangement. We conducted this study to investigate potential mechanism by which the derivative of digoxin selectively antagonizes RORγt transcriptional activity. Method Using molecular docking in combination with molecular electrostatic potential (MEP), we detected the interaction between the derivative of digoxin (Dhd) and ROR transcription factor (RORα,RORβ and RORγt), and the results were further confirmed by bioluminescent assay. Result Molecular docking demonstrated that Dhd could exclusively inhibit the conformation of RORγt;bioluminescent assay further indicated that RORγt was selectively antagonized by Dhd in a dose- and time-dependent manner. Conclusion Dhd can selectively suppress RORγt transcriptional activity.

Objective:To explore the difference of inflammatory factor imbalance between adolescent and adult patients with depression.Methods:A total of 30 adolescent and 30 adult patients with depression, and 30 adolescent and 30 adult healthy controls were included from January 2022 to August 2023. Interleukin-6 (IL-6), interleukin-17 (IL-17), transforming growth factor-beta1(TGF-β1), interleukin-10(IL-10) and Maresin-1(MaR1) level were detected by enzyme-linked immunosorbent assay. 24-item Hamilton depression scale (HAMD-24) was used to assess the severity of depression in all depressed patients. SPSS 26.0 statistical software was used for t-test, covariance analysis, Spearman analysis and multivariate binary logistic regression, and the predictive value of selected inflammatory factors in depression was evaluated by receiver operating characteristic(ROC) curve. Results:(1)In adolescent group, the levels of IL-6 ((64.000±38.632) pg/mL), IL-17((239.132±49.757) pg/mL), and TGF-β1((737.267±328.447)pg/mL) in patients with depression were higher than those in control group((32.396±16.330)pg/mL, (214.954±42.326)pg/mL, (454.542±297.194)pg/mL, all P<0.05), while the level of MaR1((21 381.301±3 946.011)pg/mL) was significantly lower than that in control group((30 130.138±10 278.999)pg/mL)( P<0.001). The level of IL-17 was positively correlated with the total score of HAMD-24 ( r=0.429) and the course of disease ( r=0.571), the level of IL-10 was negatively correlated with body weight factor score ( r=-0.384), and the levels of TGF-β1 was negatively correlated with anxiety/somatization factor score ( r=-0.449)(all P<0.05) in adolescent patients with depression.MaR1( B=0.000 1, OR=0.999 8, AUC=0.794, P<0.05) was an independent risk factor for adolescents depression.(2)In adult depression group, the levels of IL-6, IL-17, IL-10, TGF-β1 and MaR1 were higher than those in adult control group(all P<0.05). The level of TGF-β1 in adult depression group was negatively correlated with the total score of HAMD-24 ( r=-0.427), the score of anxiety/somatization factor ( r=-0.368), the score of blocking factor ( r=-0.405), and the score of hopelessness factor ( r=-0.398).The level of MaR1 was positively correlated with the age of onset of disease ( r=0.425)(all P<0.05) in adult patients with depression.MaR1( B=0.000 4, OR=1.000 3, AUC=0.874, P<0.001) and IL-6( B=0.040, OR=1.040 7, AUC=0.779, P<0.05) were independent risk factors for adult depression.The AUC of IL-6 combined with MaR1 was 0.938. Conclusion:There are differences in the underlying mechanism of immune imbalance between adolescent and adult patients with depression.MaR1 may be a diagnostic biomarker for depression in adolescents and adults.

Objective:To observe the effects of sacubitril/valsartan (LCZ696) on viral replication and cardiomyocyte apoptosis in mice with coxsackievirus B3 (CVB3)-induced viral myocarditis (VMC) and to analyze the underlying mechanisms.Methods:Forty BALB/c mice were randomly divided into four groups with 10 in each group: Sham, Sham+ LCZ696, VMC, and VMC+ LCZ696 groups. VMC model was established by intraperitoneal injection of 0.1 ml of CVB3 with a concentration of 10 6 TCID 50/ml into BALB/c mice, while the sham intervention was an equal volume of saline. The day of virus injection was defined as day 0. LCZ696 was administered by gavage at a dose of 60 mg/kg every day for seven consecutive days starting from day 1. Mouse survival rates were calculated. Echocardiography was used to evaluate the cardiac function of mice. The level of creatine kinase-MB (CK-MB) was detected by ELISA. Western blot was used to detect the levels of inflammatory cytokines (IL-6, TNF-α), apoptosis-related proteins (caspase-3, cleaved-caspase-3, Bax, Bcl-2), CVB3 surface protein (VP-1) and p-AKT/AKT in the hearts of mice. CVB3 mRNA in mouse hearts was measured by PCR. Inflammatory cell infiltration and cell apoptosis in mouse hearts were observed by HE staining and TUNEL staining, respectively. Results:Compared with the Sham group, the mice in the VMC group had a decreased survival rate and impaired cardiac function ( P<0.05). The levels of CK-MB, IL-6, TNF-α, cleaved-caspase-3/caspase-3, Bax/Bcl-2, VP-1, and CVB3 mRNA in the hearts of VMC mice increased significantly ( P<0.05), accompanied by increased expression of AKT, decreased phosphorylation of AKT ( P<0.05) and increased cell apoptosis. LCZ696 reversed the above changes. It could increase the survival rate, improve the cardiac function ( P<0.05), decrease cardiac inflammation, cell apoptosis and viral replication ( P<0.05), and increase the phosphorylation of AKT ( P<0.05). LCZ696 had no significant effects on the survival rate, cardiac function, myocardial injury, cardiac inflammation, cell apoptosis, viral replication or the expression of PI3K/AKT signaling pathway-related proteins in normal mice. Conclusions:LCZ696 could significantly inhibit cardiomyocyte apoptosis and reduce CVB3 replication in the hearts of VMC mice by regulating the PI3K/AKT pathway, thereby improving mouse cardiac function and survival rate.

Objective:To analyze the clinical and imaging features of patients with COVID-19-related osmotic demyelination syndrome (ODS).Methods:COVID-19-related ODS cases diagnosed in the Department of Neurology, Peking Union Medical College Hospital from January 2020 to September 2023 were retrospectively reviewed. And their past medical history, possible triggers, clinical manifestations, imaging manifestations, treatment and prognosis were summarized.Results:A total of 5 patients with COVID-19-related ODS were included. Electrolyte disturbances acted as an inducement of ODS in all patients (5/5),4 of whom with hyponatremia. Four of 5 patients first presented with disturbance of consciousness, followed by predominant dystonia. Imaging of all patients (5/5) showed isolated extrapontine myelinolysis (EPM). With the prolongation of the course of disease, such signal intensity could return to normal, and lesions showed atrophic changes in some patients. The patients′ clinical symptoms were partly relieved within a few days to a few months after treatment.Conclusions:COVID-19-related ODS is mostly associated with hyponatremia, and EPM is more common. COVID-19 should be considered as a risk factor for ODS.

The traditional view is that breast reconstruction is not an option for day surgery center. As a result, few hospitals in the world conduct this operation in day surgery center. Endoscopic breast reconstruction with liposuction and robot-assisted breast reconstruction are minimally invasive surgeries for breast cancer patients, but they cannot be carried out in the day surgery center due to long operation time. The novel endoscopic-assisted immediate implant-based breast reconstruction after nipple sparing mastectomy through a single axillary incision for breast cancer patients has been successfully conducted in the day surgery center in our hospital due to short operation time and small trauma. Standardized management of the complete process from the patient selection to follow-up after discharge brings rapid recovery and few complications. At the same time, the development of endoscopic surgery makes the breast almost scarless and improves aesthetic results. Therefore, the mode of endoscopic-assisted reconstruction in the day surgery center of our hospital is expected to be popularized in the whole country.

Objective    To explore the surgical technique and preliminary results of endoscopic nipple-sparing mastectomy (E-NSM) and immediate pre-pectoral implant-based breast reconstruction (BR) with titanium-coated polypropylene mesh (TiLoop Bra) via single axillary incision for breast cancer patients. Methods    The clinical data of 9 consecutive female patients who underwent E-NSM and immediate pre-pectoral implant-based BR with TiLoop Bra from  March to May 2021 were retrospectively analyzed. The mean age of patients was 40.6 (22-60) years. The operation time, early complications were collected, and the patients' social and mental health, breast satisfaction and chest function before and after the operation were assessed with the BREAST-Q questionnaire. Results    All the patients had unicentric tumor with a mean diameter of 2.4 (0.6-4.7) cm. The mean distance from the tumor to the nipple was 2.5 (2-4) cm. There were 2 patients with tumor stage 0 and 7 patients with stageⅠ. The mean operation time was 161.1 (125-201) min, the mean blood loss was 41.1 mL and the hospital stay time was 1.5 d. There were 5 patients in the day-care unit. All the patients were successfully followed up with a median follow-up time of 1 (1-2) month. One (11.1%) patient with depigmentation of the nipple-areola complex caused by mild ischemia. None of the patients had incision complications, subcutaneous emphysema, hematoma, infection, nipple-areola or skin flaps necrosis, implant loss. During the follow-up period, no local/regional recurrence or distant metastasis was found. Chest well-being was decreased in the first month after the surgery compared with preoperative status, and the difference was statistically significant (P=0.001). There was no statistical difference in the breast satisfaction or psychosocial function scores between pre- and post-operation (P>0.05). Conclusion    E-NSM and immediate pre-pectoral implant-based BR with TiLoop Bra via single axillary incision has minimal trauma, rapid postoperative recovery, short operation time, few early complications and good early cosmetic effect, and the short-term result is satisfactory.