Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

Depression is a severe mental illness. Although existing antidepressant medications have shown efficacy in many patients, a significant proportion show poor responses to current treatments, necessitating the need for novel therapeutic approaches. Photobiomodulation (PBM), an emerging physical therapy, has recently shown promising efficacy in the treatment of depression, as indicated by two systematic reviews, and is characterized by high safety and good tolerability. However, challenges remain in areas such as light delivery techniques and optimization of treatment parameters. This review summarizes the antidepressant mechanisms of PBM, various methods of light transmission, and recent research progress on its application in the treatment of depression. It also discusses issues related to safety, tolerability, and impact of specific parameters, aiming to provide insights and recommendations for future research on PBM as a therapy for depression.

Objective:To investigate the clinical manifestation, therapy, and prognosis of Susac syndrome and enhance the understanding of this disease.Methods:A case summary was made.The clinical data of two siblings with Susac syndrome treated at Children′s Medical Center, Peking University First Hospital in January 2024 were summarized.Reported cases of pediatric Susac syndrome were reviewed.Results:The onset of the disease in the two siblings was at the age of 3.00 and 6.75 years, with recurrent headaches, tinnitus, hearing loss and encephalopathy symptoms.Cranial magnetic resonance imaging showed multiple cerebral microbleeding and microinfarction lesions, " snowball like" in the corpus callosum and diffuse white matter edema in the brain.Audiometry revealed sensorineural hearing loss.In one case, ophthalmic fluorescein angiography revealed ischemic changes due to branch retinal artery occlusions.No pathogenic variants were detected in gene testing.This child was diagnosed with Susac syndrome, and the symptoms were improved after treatment with Corticosteroids and Rituximab.No relapse was observed during the 9-month follow-up.A total of 20 pediatric cases of Susac syndrome were retrieved, including 18 reported previously and 2 cases from this study.There were 2 boys and 18 girls, with the age of onset ranging from 2.5 to 17.0 years.The common initial symptoms included headache (19 cases), vertigo and tinnitus or hearing loss (9 cases), and vision impairment or visual field defect (4 cases). The symptoms were improved after immunotherapy.Conclusions:With a low incidence, Susac syndrome is rare in children and difficult to diagnose.There may be a genetic predisposition in such disease.Early diagnosis and immunotherapy can low the relapse and improve the prognosis.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Objective:To investigate the clinical manifestation, therapy, and prognosis of Susac syndrome and enhance the understanding of this disease.Methods:A case summary was made.The clinical data of two siblings with Susac syndrome treated at Children′s Medical Center, Peking University First Hospital in January 2024 were summarized.Reported cases of pediatric Susac syndrome were reviewed.Results:The onset of the disease in the two siblings was at the age of 3.00 and 6.75 years, with recurrent headaches, tinnitus, hearing loss and encephalopathy symptoms.Cranial magnetic resonance imaging showed multiple cerebral microbleeding and microinfarction lesions, " snowball like" in the corpus callosum and diffuse white matter edema in the brain.Audiometry revealed sensorineural hearing loss.In one case, ophthalmic fluorescein angiography revealed ischemic changes due to branch retinal artery occlusions.No pathogenic variants were detected in gene testing.This child was diagnosed with Susac syndrome, and the symptoms were improved after treatment with Corticosteroids and Rituximab.No relapse was observed during the 9-month follow-up.A total of 20 pediatric cases of Susac syndrome were retrieved, including 18 reported previously and 2 cases from this study.There were 2 boys and 18 girls, with the age of onset ranging from 2.5 to 17.0 years.The common initial symptoms included headache (19 cases), vertigo and tinnitus or hearing loss (9 cases), and vision impairment or visual field defect (4 cases). The symptoms were improved after immunotherapy.Conclusions:With a low incidence, Susac syndrome is rare in children and difficult to diagnose.There may be a genetic predisposition in such disease.Early diagnosis and immunotherapy can low the relapse and improve the prognosis.

To investigate the current status of sleep quality among nurses in tertiary hospitals in China, analyze the correlations of work stress and perceived organizational support with the risk of sleep problems, and further examine the mediating effect of perceived organizational support between work stress and sleep problems in nurses.

OBJECTIVE: To investigate the effect and mechanism of Shuangshi Tonglin Capsules (SSTL) in the treatment of prostate fibrosis (PF). METHODS: Human prostate stromal cells (WPMY-1) were used for in vitro experiments to establish PF cell models induced with estradiol (E₂). The cell proliferation, migration and clonogenic capacity were determined by cell counting kit-8, scratch assay, and crystal violet staining, respectively. Sprague-Dawley rats were used for in vivo experiments. The changes in histomorphology and organ index of rat prostate by SSTL were determined. Pathologic changes and collagen deposition changes in rat prostate were observed by haematoxylin and eosin (HE) and Masson staining. Enzyme-linked immunosorbent assay kits were used to determine changes in rat PF markers fibroblast growth factor-23 (FGF-23), E₂ and prostate specific antigen (PSA). Mechanistically, changes in oxidative stress indicators by SSTL were determined in WPMY-1 cells and PF rats. Then the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and transforming growth factor-β1 (TGF-β1)/Smad pathway-related proteins as well as Nrf2 and TGF-β1 mRNA were further detected by Western blot or quantitative real-time polymerase chain reaction both in vivo and in vitro. RESULTS: In the efficacy study, SSTL significantly reduced the proliferation, migration, and clonogenic ability of cells, improved the morphology of the glandular tissue, significantly reduced the prostate index, reduced glandular fibrous tissue and collagen deposition, and resulted in a significant decrease in the levels of FGF-23, E₂ and PSA (P<0.01 or P<0.05). In the mechanistic study, SSTL ameliorated oxidative stress by significantly increasing superoxide dismutase and glutathione peroxidase levels and decreasing malondialdehyde level in WPMY-1 cells and rats (P<0.01 or P<0.05). SSTL significantly elevated the expressions of Nrf2, HO-1, NAD(P)H quinone oxidoreductase 1 (NQO-1), and Smad7 proteins in both cells and rats, and significantly decreased the expressions of TGF-β1, collagen I, α-smooth muscle actin and Smad4 proteins (P<0.01 or P<0.05). SSTL also elevated the content of Nrf2 mRNA and decreased the content of TGF-β1 mRNA in cells and rats (P<0.01 or P<0.05). The Nrf2 inhibitor ML385 was added in in vitro experiments to further validate the pathway relevance. CONCLUSION SSTL was effective in improving PF in vivo and in vitro, and its mechanism of action may function through the Nrf2/TGF-β1 signaling pathway.
Male ; NF-E2-Related Factor 2/metabolism* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Humans ; Fibrosis ; Prostate/drug effects* ; Cell Proliferation/drug effects* ; Capsules ; Cell Movement/drug effects* ; Oxidative Stress/drug effects* ; Rats

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective To construct a model combining with traditional Chinese medicine(TCM)syndrome for predicting the risk of disease progression in patients with idiopathic membranous nephropathy(IMN)by machine learning methods,thus to quantitatively evaluating the value of TCM syndrome in the prediction of the risk of disease progression in IMN.Methods Monofactor analysis,recursive feature elimination(RFE)and multivariate binary Logistic regression analysis were used to screen the independent related factors affecting the risk of disease progression of IMN,and then a risk prediction model was constructed.A total of 102 patients with IMN were randomly assigned to the training set and the test set in a ratio of 65∶35,and then the comparison was conducted in the performance indicators of accuracy,sensitivity,specificity,F1 value,and area under the receiver operating characteristic(ROC)area under the curve(AUC)of the risk prediction model with or without the inclusion of the TCM syndrome information.Results Before the inclusion of TCM syndrome information,12 clinical characteristic variables for patients with MN were obtained after monofactor analysis combined with RFE screening,and they were age,hemoglobin quantification,urinary occult blood,24-hour urine protein quantification,urine protein-creatinine ratio,estimated glomerular filtration rate(eGFR),creatinine,uric acid,alanine transaminase,anti-phospholipase A2 receptor antibody(PLA2R-Ab),total cholesterol,and low-density lipoprotein cholesterd.A risk cholesterol prediction model containing the above variables was constructed.The multivariate binary Logistic regression analysis showed that the differences of the clinical variables mentioned above between the training-set group and test-set group were statistically significant,and the risk prediction model presented good sensitivity and predictability.Monofactor analysis combined with RFE screening was performed again after the inclusion of TCM syndrome information,and then 14 variables were obtained,which included blood stasis syndrome and dampness obstruction syndrome.The sensitivity and specificity of the model with the inclusion of the TCM syndrome information were significantly improved when compared with those without the inclusion of TCM syndrome information.Conclusion The results of the study initially indicate that TCM syndrome can be used as an important supplementary variable for predicting the risk of disease progression in IMN,and will provide a reference for intelligent diagnosis through the integration of traditional Chinese and western medicine information,and will supply the guidance for the treatment of IMN with TCM.

Objective To investigate the role of the neutrophil-to-lymphocyte ratio(NLR)in predicting the in-hospital mortality risk of patients with acute aortic dissection(AAD)in multicenter hospitals.Methods A multicenter retrospective cohort study was conducted.Clinical data were collected from 2642 AAD patients who were hospitalized in five teaching hospitals:Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology,Henan Provincial People's Hospital,Fuwai Central China Cardiovascular Hospital,the Third Affiliated Hospital of Xinxiang Medical University,and the Second Affiliated Hospital of Chongqing Medical University between August 2010 and December 2021.According to the quartiles of serum NLRlevels,the patients were divided into four groups:first quartile(Q1,n=660),second quartile(Q2,n=661),third quartile(Q3,n=661),and fourth quartile(Q4,n=660).The clinical characteristics and biochemical indicators of each group were compared.Partial correlation analysis was used to assess the relationship between NLR and cardiovascular parameters.Restricted cubic splines,Kaplan-Meier survival analysis,and Cox regression models were employed to evaluate the association between NLR levels and in-hospital mortality risk in AAD patients.Results The median age of all patients was 54[interquartile range(IQR):46-63]years,including 2096 males and 546 females.Compared with Q1-Q3 groups,patients inQ4group had a lower incidence of smoking history and diabetes history,and were more likely to have DeBakey type Ⅰ AAD(P＜0.05).Additionally,the levels of aspartate aminotransferase,high-density lipoprotein cholesterol,creatinine,and D-dimer in Q4 group were higher,while the levels of triglycerides and C-reactive protein(CRP)were lower(P＜0.01).The results of partial correlation analysis showed that the plasma NLR level was positively correlated with D-dimer(r=0.43,P＜0.01)and creatinine(r=0.16,P＜0.01).The restricted cubic spline function in the Cox model revealed a significant non-linear relationship between the plasma NLR level and clinical outcomes in AAD patients(P＜0.01).Kaplan-Meier survival analysis indicated that patients in Q4 group had the highest in-hospital mortality rate compared with Q1-Q3 groups(P＜0.0001).Furthermore,multivariate Cox regression analysis demonstrated that compared with Q1 group,the hazard ratio(HR)of NLR in Q4 group was 1.77(95％CI 1.33-2.37,P＜0.001),which was an independent risk factor for the primary endpoint events.Conclusion A higher plasma NLR level is significantly associated with the occurrence of cardiovascular events in AAD patients,and this association remains significant even after adjusting for potential confounding factors such as the multicenter visiting hospitals.