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.

The incidence of allergic diseases in children is increasing, which has become a serious public health burden.Studies have shown that the interaction between the human body and microorganisms contributes to the establishment of immune tolerance.This evidence supports the use of microbial agents for the prevention and treatment of allergic diseases.Bacterial lysates (BLs) are immunomodulators composed of inactivated extracts of a variety of bacteria associated with respiratory tract infections.BLs act on the mucosal immune system and initiate downstream immune responses by activating dendritic cells, thereby restoring T helper cell 1/T helper cell 2 balance.Relevant studies have confirmed that BLs can alleviate the clinical symptoms of allergic diseases and may play a role in primary prevention.The immunomodulatory effect of BLs is affected by many factors such as product type, administration method, and administration regimen.In clinical application, the patient′s immune status should be evaluated to avoid immune exhaustion.This review summarizes the mechanism, clinical research progress and administration regimen of BLs, in order to provide evidence for clinical application.

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 explore the application effect of healthcare failure mode and effect analysis (HFMEA) in nursing risk management of emergency surgery for patients with traumatic brain injury (TBI). Methods Taking the HFMEA model as the theoretical framework, the emergency surgical process of TBI was analyzed, a flow chart was drawn, and the potential risk factors were analyzed. Corresponding intervention programs were adopted for high-risk failure modes, and 80 patients from November 2022 to April 2023 were conducted with routine management before implementation of HFMEA (control group), the other 80 patients from May to October 2023 were conducted with management after implementation of HFMEA (observation group). The surgical efficiency (preoperative waiting time, surgical preparation time, anesthesia induction time, postoperative handover time), the incidence rates of adverse events in the operation room (incomplete preparation of supplies, contamination of surgical drapes, insufficient or defective intraoperative instruments, errors in writing nursing records, incorrect or missing items in handover information), the incidence rates of perioperative complications (low intraoperative body temperature, pressure injury, abnormal fluctuations in vital signs during surgery, wound infection, lung infection) and satisfaction degree of surgical doctors to nurses for current operations (itinerant nurses, instrument nurses) were compared between two groups. Results The observation group had significantly shorter preoperative waiting time, surgical preparation time, anesthesia induction time, and postoperative handover time compared to the control group (P < 0.01). The incidence rate of adverse events in the operation room for the observation group was 16.25%, which was significantly lower than 46.25% of the control group (P < 0.01). The incidence rate of complications was 8.75% in the observation group, which was significantly lower than 26.25% in the control group (P < 0.01). Satisfaction degree of the doctors to nurses for the current operation in the observation group was significantly higher than that in the control group (P < 0.05). Conclusion Application of the HFMEA model in the perioperative nursing management of patients with emergency surgery for TBI can effectively improve surgical efficiency, reduce the incidence rates of nursing-related adverse events and complications, and enhance satisfaction degree of doctors to nurses in operation room.

Objective:To evaluate the safety and effectiveness of transjugular intrahepatic portosystemic shunt (TIPS) in hepatocellular carcinoma (HCC) patients with Vp4 portal vein tumor thrombus (PVTT).Methods:Data of 15 patients undergoing TIPS for HCC with Vp4 PVTT and portal hypertension (PTN) in Peking University First Hospital from July 2018 to February 2023 were retrospectively analyzed, including 14 males and 1 female, aged (61.5±11.1) years old, ranging from 40 to 78 years old. The success rate of TIPS, portal pressure gradient (PPG) before and after procedure, perioperative adverse effects and complications were recorded. The survival status of patients was followed up by telephone review after surgery. Kaplan-Meier method was used for survival analysis.Results:The procedure of TIPS was performed uneventfully in all patients, with a technical success rate of 100% (15/15). PPG before and after TIPS were (31.73±5.48) mmHg (1 mmHg=0.133 kPa) and (17.60±3.66) mmHg, respectively, and the difference was statistically significant ( P<0.001). No perioperative death, hepatic artery or bile duct injury, acute liver failure or other major complications occurred. Compared with the preoperative status, the performance status scores [0(0, 0) vs. 3(3, 3)] and Child-Pugh scores [6(5, 8) vs. 9(8, 10)] were lower in patients one month after TIPS (all P<0.05). The median survival time was 228 d. Kaplan-Meier curves showed that the cumulative survival rates at 3, 6, 12 and 24 months after TIPS were 100%, 64.3%, 32.7% and 8.2%, respectively. Conclusion:TIPS could be safe and effective for HCC with Vp4 PVTT and severe PTN.

Objective:To investigate the changes in the nerve fiber layer of the cornea in patients with demyelinating optic neuritis (DON) and its correlation with visual acuity.Methods:A cross-sectional study. From March 2021 to July 2022, 27 cases (39 eyes) of DON patients diagnosed in the Department of Neurology and Ophthalmology of Beijing Tongren Hospital Affiliated to Capital Medical University were enrolled in this study. According to the serological test results, the patients were divided into aquaporin 4 antibody associated optic neuritis (AQP4-ON group) and myelin oligodendrocyte glycoprotein antibody associated optic neuritis (MOG-ON group), with 15 cases (19 eyes) and 12 cases (20 eyes) respectively. According to previous history of glucocorticoid treatment, the patients were divided into glucocorticoid treated group and non-glucocorticoid treated group, with 17 cases (27 eyes) and 10 cases (12 eyes) respectively. Twenty healthy volunteers (20 eyes) with age- and gender-matched were selected as the control group. All eyes underwent best corrected visual acuity (BCVA) and in vivo confocal microscopy (IVCM) examinations. BCVA was performed using Snellen's standard logarithmic visual acuity chart, which was converted into logarithmic minimum angle resolution (logMAR) visual acuity during statistics. The corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve fiber branch length (CNBL), corneal nerve fiber branch density (CNBD) and the density of corneal dendritic cells (DC) were detected by IVCM examination. Parameter comparison between groups by t-test and Kruskal-Wallis rank sum test. The correlation between logMAR BCVA and pamameters of corneal nerve fibers were analyzed using Spearman analysis. Results:The CNFL, CNFD, and CNBL of the DON group and the control group were (10.67±2.55) mm/mm 2, (57.78±12.35) root/mm 2, (3.27±1.34) mm/mm 2, and (13.74±3.05) mm/mm 2, (70.95±13.14) root/mm 2, and (4.22±1.03) mm/mm 2, respectively; the difference in CNFL, CNFD, and CNBL between the two groups were statistically significant ( t=4.089, 3.795, 2.773; P<0.05). The CNFL, CNBL, and CNBD of the affected eyes in the MOG-ON group and AQP4-ON group were (12.02±2.13) mm/mm 2, (3.80±1.19) mm/mm 2, (47.97±8.86) fibers/mm 2, and (9.25±2.19) mm/mm 2, (2.72±1.19) mm/mm 2, (39.43±13.86) fibers/mm 2, respectively; the differences in CNFL, CNBL, and CNBD between the two groups were statistically significant ( t=-4.002, -2.706, -2.306; P<0.05). The corneal DC density of the patients in the hormone treated group and the non-hormone treated group was (24.43±8.32) and (41.22±9.86) cells/mm 2, respectively. The difference in corneal DC density between the two subgroups was statistically significant ( P<0.001). Correlation analysis showed that there was a significant negative correlation between logMAR BCVA and CNBL and CNFL in patients with DON ( r=-0.422, -0.456; P<0.05). Conclusions:There are different degrees of corneal nerve fiber damage in patients with different types of DON. There was a negative correlation between BCVA and the length of corneal nerve fibers.

Objective:To observe the changes of serum cytokines in patients with neuromyelitis optic neuromyelitis optic spectrum disorder (NMOSD) associated optic neuritis (NMOSD-ON) before and after intravenous methylprednisolone pulse (IVMP) treatment.Methods:A prospective clinical study. From November 2020 to December 2021, 24 NMOSD-ON patients who visited the Neuro-Ophthalmology Clinic of Beijing Tongren Hospital Affiliated to Capital Medical University were included. Among them, 9 patients were male; 15 patients were female. According to the detection results of aquaporin 4 (AQP4) immunoglobulin G (IgG) antibody (AQP4-IgG) in peripheral blood, the patients were divided into AQP4-lgG positive group and AQP4-lgG negative group, which were 10 and 14 cases respectively. Twenty healthy volunteers were selected as control group. Age ( F=0.639) and sex ( χ2=2.373) composition ratio of the three groups were compared, the difference were not statistically significant ( P=0.504, 0.333). All patients were treated with 500 mg/d or 1 000 mg/d IVMP. Peripheral venous blood of all subjects, and quantitatively analyze interferon-gamma (IFN-γ), interleukin (IL)-4, IL-31, IL-33, IL-17A, IL-6, IL-21, IL-23, IL-10, tumor necrosis factor (TNF)-α level in serum with Luminex FLEX MAP 3D liquid-phase suspension chip detection system were collected. The differences among groups were analyzed by one-way ANOVA and Kruskal Wallis H test. Results:Before IVMP treatment, serum IL-17A concentrations in AQP4-lgG positive group, AQP4-lgG negative group and control group were 2.39, 2.17 and 1.97 pg/ml, respectively. TNF-α concentrations were 5.60, 4.17 and 5.89 pg/ml, respectively. Compared with control group, serum IL-17A concentration in AQP4-IgG positive group was increased, while TNF-α concentration in AQP4-IgG negative group was decreased, with statistical significance ( H=12.720, 10.900; P=0.040, 0.039). The levels of IL-17A, IL-6 and other cytokines did not change significantly. After IVMP treatment, serum IL-6 in AQP4-lgG positive group and AQP4-lgG negative group were 0.72 pg/ml and 0.73 pg/ml, respectively. TNF-α concentrations were 4.17 pg/ml and 3.88 pg/ml, respectively. IFN-γ concentrations were 2.15 pg/ml and 2.55 pg/ml, respectively. Compared with before treatment, serum levels of IL-6, TNF-α and IFN-γ in AQP4-lgG positive patients were significantly decreased, with statistical significance ( Z=-2.668, -2.547, -2.201; P=0.008, 0.011, 0.028). Serum levels of IL-6 and TNF-α were significantly decreased in AQP4-lgG negative patients, and the difference was statistically significant ( Z=-2.501, -1.978; P=0.012, 0.048). Conclusion:Glucocorticoid may play a therapeutic role by affecting the levels of serum IL-6, TNF-α, IFN-γ in patients with NMOSD-ON.

Objective:To analyze the prognostic factors of vision of myelin oligodendrocyte glycoprotein (MOG) antibody positive associated optic neuritis (ON) after methylprednisolone pulse therapy.Methods:A clinical observational study. A total of 32 patients (47 eyes) with MOG antibody positive ON were observed and followed up in the ophthalmology department of Beijing Tongren Hospital Affiliated to Capital Medical University and Beijing Puren Hospital from March 2019 to January 2022. Clinical data including the best corrected visual acuity (BCVA) and orbital magnetic resonance imaging were recorded. The BCVA was examined by Snellen visual acuity chart, which was finally converted into the logarithm of the minimal angle of resolution (logMAR) for statistical analysis. There were 22 case (38 eyes) with complete image data. All patients were treated with intravenous methylprednisolone pulse (IVMP) for 3-5 days. According to the intervention time (from onset to glucocorticoid treatment), the patients were divided into three groups: <7 d group, 7-14 d and> 14 d group, with 16, 13, 11 eyes, respectively. The median follow-up time was 28 months. After 1 week, 1, 3 and 6 months treatment, the same equipment and methods were used for relevant examinations to observe the changes of visual acuity and the factors influencing the prognosis of visual acuity after IVMP treatment. Logistic regression and linear regression were used to analyze the prognostic correlation factors. Receiver operating characteristic (ROC) curve was used to determine the critical cut-off point of intervention timing.Results:Among the patients, 16 were male and 16 were female. The median onset age was 26 years. The onset duration time was 5-60 days. There were 18 cases (56.3%, 18/32) with abnormal serum immune indexes. The initial symptom was decreased vision with unilateral or bilateral ON. Seventeen (53.1%, 17/32) cases had unilateral ON and 15 (46.9%, 15/32) cases with bilateral ON. Thirty-six eyes (76.6%, 36/47) got optic disc edema, 37 eyes (78.7%, 37/47) accompanied by pain of ocular movement. The nadir logMAR BCVA was mean 1.69±0.13. Long T2WI signals with segmental thickening in the orbital segment of the optic nerve were obtained in 27 eyes (71.1%, 27/38) and in 24 eyes (63.2%, 24/38) with optic nerve and sheath enhancement. During the follow-up period, there were 10 cases of relapse (31.3%, 10/32). The logMAR BCVA of attacked eyes were 0.52±0.09, 0.22±0.06, 0.12±0.06, 0.10±0.06 at 1 week and 1, 3 and 6 months after IVMP treatment, respectively. The rate of BCVA improvement was the fastest at 1 week after treatment, and BCVA returned to stability at 3 months. Logistic regression analysis showed that the timing of intervention was significantly correlated with the prognosis of vision in primary onset patients (odds ratio=12.17, P=0.006), with a negative linear regression relationship ( r=-0.48, 95% confidence interval -0.71--0.17, P=0.008). Comparing the logMAR BCVA between the intervention time >14 group with the <7 group and the 7-14 group, there were statistically significant difference ( P=0.017, 0.037), respectively. The cut-off point of ROC curve to predict the optimal intervention time was 13.5 days. Other factors such as: gender, age, predisposing factor, pain of eye motion, edema of optic disc, bilateral ON, imaging changes, abnormal autoimmune indicators were not associated with the prognosis of visual acuity. Conclusion:The timing of hormone intervention in primary onset patients is an important factor affecting the prognosis of vision and the optimal intervention time window of IVMP is two weeks.

Leber's hereditary optic neuropathy (LHON) is a rare hereditary optic nerve disease. At present, the understanding of its etiology and pathogenesis is relatively clear. With the emergence of new drugs such as idebenone and the possibility of gene therapy for LHON, it has brought hope for patients to recover. However, because genetic testing technology has not been widely developed in China, clinical misdiagnosis of LHON as optic neuritis still occurs from time to time. How to make timely identification and correct diagnosis of LHON still poses certain challenges for Chinese ophthalmologists. In addition, in terms of treatment, the choice of treatment methods and treatment costs in the pre-onset (gene mutation carriers) and different periods after the onset of LHON are also huge challenges for patients and their families.

Objective To establish an analysis method for quantitatively determining phenolic character-istic components and correlation analyzing their quality representation of specific chromatograms in Shaji (Seabuckthorn Fruit,Hippophae rhamnoides),and to review the quality of Shaji effectively and accurate-ly by applying association analysis-reviewing mode.Methods HPLC-PDA method was used to quantita-tively determine the content of phenolic characteristic components in 11 batches of Shaji(protocatechuic acid,ellagic acid,narcissin,quercetin,isorhamnetin),and to establish phenolic specific chromatograms of Shaji.The quality of 11 batches of Shaji was characterized based on teasing characteristic peaks and chemical types.The quantity of 11 batches of Shaji was characterized based on quantity and peak areas of protocatechuic acid, ellagic acid, narcissin, quercetin, isorhamnetin, phenolic acids(represented by protocatechuic acid)and flavonoids(represented by narcissin)in the specific chromatograms.The characterized results of quality and quantity of 11 batches of Shaji were given association analysis based on baseline material of Shaji.Results The characteristic components of protocatechuic acid, ellagic acid,narcissin,quercetin,isorhamnetin all had good linear correlation,and the results of methodological investigation were in accordance with the quantitative determination requirements.Taken batch 7 of Shaji as baseline material, there were totally 18 characteristic peaks in phenolic specific chromatograms of Shaji,including 3 peaks of phenolic acids and 15 peaks of flavonoids, and all 18 characteristic peaks appeared in the chromatograms of 11 batches of Shaji.The quantity of characteristic components were higher in batch 8, 7, 10, 4, 5, 11 and 1 after analyzed and reviewed by using association analysis-reviewing mode.The relevance of batch 6, 2, 3, 1 and 11 was the highest with baseline material of Shaji.Comprehensive reviewing showed that the excellent extents of batch 1,11,8,6 and 7 were prior. Conclusion The quantitative determination method of phenolic characteristic components in Shaji estab-lished in this study is easy and accurate.The association analysis-reviewing mode for quality characteriza-tion of phenolic specific chromatograms can be used for analyzing the quality and application validity of Shaji and reviewing quality of Shaji effectively and accurately.