The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

To explore the effectiveness of "near peer learning" (NPL) in the electromyography(EMG)teaching module for neurology residents.

Objective:To find out how newly recruited nurses feel about the use of scenario simulation teaching in communication skill training, and to provide references and lessons for improving and perfecting the training of newly recruited nurses.Methods:Purposive sampling method was used to select 10 nurses who were newly recruited to a tertiary grade A hospital in Shanghai in July 2023 for semi-structured interviews. Colaizzi's 7-step analysis method was used to collate and analyze the data and develop themes.Results:Three themes were extracted from the feelings of newly recruited nurses about scenario simulation teaching, which were the improvement of learning ability, the cultivation of clinical comprehensive ability, and the improvement of communication and teamwork ability.Conclusions:Scenario simulation teaching can improve the clinical communication ability of newly recruited nurses and enhance their learning ability and comprehensive clinical ability. This study designed a scenario simulation teaching program oriented and targeted to highlight communication ability, which further proved its positive significance. However, attention needs to be paid to the construction of clinical teaching team, evaluation system, and feedback mechanism for targeted improvement to enhance the teaching effect.

Objective To explore the correlation between hyponatremia at admission and all-cause mortality within one year after discharge in elderly patients with intestinal obstruction.Methods The 331 cases of elderly patients with intestinal obstruction(aged ≥ 60 years)who visited the General Surgery Department of Nanjing Meishan Hospital from January 2017 to December 2020 were selected as the research objects for retrospective cohort study analysis.According to the patient's blood sodium level at admission,they are divided into two groups:the hyponatremia group(Na＜135 mmol/L)and the non hyponatremia group(Na≥135 mmol/L).Divided into death group and survival group based on whether death occurred within one year after discharge.SPSS 25.0 software was used for statistical analysis.Independent sample t test,x2 test,Kaplan Meier method,and multivariate Cox regression analysis were used to observe the correlation between admission hyponatremia and all-cause mortality within one year after discharge in elderly patients with intestinal obstruction.Results A total of 331 patients were enrolled.The incidence of hyponatremia was 32.3％,and 56 deaths occurred within one year,accounting for 16.92％.The one-year mortality rate in the hyponatremia group was 23.4％(25/107),which was higher than 13.8％(31/224)in the non hyponatremia group.The difference was statistically significant(P＜0.05).The survival analysis(Kaplan Meier)results showed that the survival rate of the hyponatremia group was lower than that of the non hyponatremia group(Log Rank P＜0.05).After adjusting for other confounding factors in multivariate Cox regression analysis,hyponatremia(HR=1.88,95％CI:1.07-3.29)was an independent risk factor for one-year all-cause mortality in elderly patients with intestinal obstruction(P＜0.05).Conclusion Hyponatremia at admission is an independent risk factor for all cause mortality in elderly patients with intestinal obstruction within one year after discharge.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

OBJECTIVE To analyze the effects of the national centralized drug procurement （NCDP） policy on drug availability and the structure of drug use in public hospitals. METHODS Using hypoglycemic， lipid-lowering， antiviral drugs， and psychiatric drugs for the treatment of mental illness and depression as objects， the interrupted time series model was used to quantitatively evaluate the changes in consumption sum of drugs， consumption amount and daily cost of the target drugs in national sample hospitals as well as the changes in per capita medication frequency， outpatient prescription amount， and medical insurance surplus of target drugs in a third grade class A hospital before and after the implementation of NCDP policy. RESULTS After the implementation of the NCDP policy， the volume for the four bid-winning drugs increased significantly （P＜0.01 for the remaining three categories except for hypoglycemic drugs）， but DDDc （P＜0.01） and the amount of related drugs （P＜0.001） decreased significantly. The volume for the non-winning drugs （except for lipid-lowering drugs） decreased significantly （P＜0.05）， and DDDc also decreased significantly （P＜0.05 for other 3 categories except for psychiatric drugs）； the volume （P＜0.01） and DDDc （P＜0.01 only for psychiatric drugs） for alternative drugs all increased except for antiviral drugs. The structure of drug use for different drugs was affected differently by the NCDP policy，and that of hypoglycemic drugs was affected obviously； the proportion of alternative drugs increased after centralized procurement. The outpatient prescription amount of each hospital significantly decreased after centralized procurement，and the decrease in the cost paid by the patients using lipid-lowering and antiviral drugs related to centralized procurement was greater than 0.60； the remaining medical insurance amount for bid-winning drugs was approximately 1.252 5 million yuan. CONCLUSIONS NCDP policy effectively alleviates the burden of medical expenditure and also drives the structure changes of drug use such as the substitution of generic drugs for original drugs， the growth of the volume of alternative drugs.

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Pregnancy ; Female ; Animals ; Mice ; Tetraploidy ; Blastocyst ; Embryo, Mammalian ; Cell Differentiation ; Embryonic Development

Tumor-associated macrophage (TAM) plays a key role in tumor progression and metastasis, and their properties are highly dependent on signaling stimuli in the tumor microenvironment (TME). Moreover, TAM, as a major player in tumor-related inflammation, is associated with the prognosis of multiple solid tumors. Immune checkpoint inhibitor (ICI) was found to significantly improve the survival prognosis of patients with microsatellite instability/mismatched repair deficient colorectal cancer. However, the efficacy of ICI as monotherapy is limited in the vast majority of CRC patients. Although the exact functions of TAM have not been fully elucidated, targeting TAM as a therapeutic strategy significantly enhances the efficacy of ICI in CRC, and TAM also demonstrates important value as predictive biomarkers for CRC prognosis.

Chemically defined medium is widely used for culturing mouse embryonic stem cells (mESCs), in which N2B27 works as a substitution for serum, and GSK3β and MEK inhibitors (2i) help to promote ground-state pluripotency. However, recent studies suggested that MEKi might cause irreversible defects that compromise the developmental potential of mESCs. Here, we demonstrated the deficient bone morphogenetic protein (BMP) signal in the chemically defined condition is one of the main causes for the impaired pluripotency. Mechanistically, activating the BMP signal pathway by BMP4 could safeguard the chromosomal integrity and proliferation capacity of mESCs through regulating downstream targets Ube2s and Chmp4b. More importantly, BMP4 promotes a distinct in vivo developmental potential and a long-term pluripotency preservation. Besides, the pluripotent improvements driven by BMP4 are superior to those by attenuating MEK suppression. Taken together, our study shows appropriate activation of BMP signal is essential for regulating functional pluripotency and reveals that BMP4 should be applied in the serum-free culture system.
Animals ; Bone Morphogenetic Protein 4/metabolism* ; Cell Differentiation ; Chromosomal Instability ; Endosomal Sorting Complexes Required for Transport ; Mice ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Mouse Embryonic Stem Cells/cytology* ; Pluripotent Stem Cells/cytology* ; Signal Transduction ; Ubiquitin-Conjugating Enzymes

Objective:To establish a real-time fluorescent quantitative TaqMan reverse transcription polymerase chain reaction (Real-time RT-PCR) detection method for Wuxiang virus (WUXV).Methods:All gene sequences of WUXV were downloaded from GenBank, and multi-sequence alignment analysis was performed using Mega-X. Primers and probes designed for the highly conservative region of S-segment genes were selected to evaluate the specificity, sensitivity and stability of detection reactions.Results:The established method can specifically detect WUXV and does not cross-react with various arboviruses. The lowest detection limit was 1 pfu/ml. The inter-batch variation coefficients of repeated detection cycle threshold ( Ct) of the same sample were all less than 1.00%. TaqMan RT-PCR was used to detect 30 batches of sandflies nucleic acid samples, and 7 of them showed positive amplification curve of WUXV. Conclusions:TaqMan RT-PCR with high sensitivity, specificity and repeatability has been successfully established, which can be used to screen large quantities of samples of WUXV.