To summarise the clinical experience of Professor TONG Xiaolin in treating prediabetes combined with overweight or obesity using the method of relieving depression and reducing turbidity. It is believed that prediabetes belongs to the category of "spleen-heat syndrome" in traditional Chinese medicine， and its core pathogenesis is center fullness with internal heat， while obesity is the initiating factor for exacerbating center fullness and internal heat， therefore， it is of great significance to reduce the risk of diabetes by interrupting the transformation between overweight， obesity and glucose metabolism abnormality. It is proposed that the main pathogenesis of prediabetes combined with overweight or obesity is qi depression and turbidity obstruction in middle jiao， with qi depression as the root and turbidity obstruction as the cause， forming a treatment idea with the method of relieving depression and reducing turbidity as the core. In clinic， Dahuang Huanglian Xiexin Decoction （大黄黄连泻心汤） is used as the basic prescription， with a primary focus on directing the turbid downward， supplemented by regulating qi， which embodies the concept of "promoting movement through descent， then figuring out the root of spleen-heat syndrome. Furthermore， the treatment is flexibly modified based on the patient's deficiency-excess syndrome to ensure individualized therapy.

BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

OBJECTIVE: To investigate the effects of 4-methylcatechol (4MC) on the migration and inflammatory response in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), as well as its underlying mechanisms of action. METHODS: RA-FLS was isolated from synovial tissue donated by RA patients, and the optimal concentration of 4MC was determined by cell counting kit 8 method for subsequent experiments, and the effect of 4MC on the migratory ability of RA-FLS was evaluated via a cell scratch assay. An inflammation model of RA-FLS was induced by tumor necrosis factor α (TNF-α). Real-time fluorescence quantitative PCR and ELISA were employed to detect the gene and protein expression levels of interleukin-1β (IL-1β) and IL-6 in RA-FLS and their culture supernatants, respectively, thereby investigating the anti-inflammatory effects of 4MC. Western blot was used to examine the expressions of nuclear factor κB (NF-κB) signaling pathway-related proteins, including inhibitor of NF-κB-α (IKBα), phosphorylated (P)-IκBα, NF-κB-inducing kinase α (IKKα), P-IKKαβ, P-p65, and p65. Cellular immunofluorescence was utilized to detect the expression and localization of p65 in RA-FLS, exploring whether 4MC exerts its anti-inflammatory effects by regulating the NF-κB signaling pathway. Finally, a collagen-induced arthritis (CIA) mouse model was established. The anti-RA effect of 4MC in vivo was evaluated by gross observation and histological examination. RESULTS: 4MC inhibited RA-FLS migration in a concentration-dependent manner. In the TNF-α-induced RA-FLS inflammation model, 4MC significantly decreased the gene and protein expression levels of IL-1β and IL-6. Furthermore, 4MC markedly reduced the ratios of P-IΚBα/IΚBα, P-IKKαβ/IKKα, and P-p65/p65, thereby blocking the transcriptional activity of p65 by inhibiting its nuclear translocation. This mechanism effectively suppressed the activation of the TNF-α-mediated NF-κB signaling pathway. Animal studies demonstrated that 4MC [10 mg/(kg·day)] significantly lowered serum levels of IL-1β, IL-6, and TNF-α, and alleviated arthritis severity and bone destruction in CIA mice. CONCLUSION 4MC not only inhibits the migration of RA-FLS but also mitigates their inflammatory response by suppressing the NF-κB signaling pathway, thereby effectively exerting its anti-RA effects.
Synoviocytes/metabolism* ; Arthritis, Rheumatoid/metabolism* ; Animals ; Cell Movement/drug effects* ; Humans ; Catechols/therapeutic use* ; Fibroblasts/drug effects* ; Mice ; Tumor Necrosis Factor-alpha/pharmacology* ; Interleukin-1beta/metabolism* ; Interleukin-6/metabolism* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Transcription Factor RelA/metabolism* ; Synovial Membrane/cytology* ; Cells, Cultured ; Male ; Arthritis, Experimental ; Anti-Inflammatory Agents/pharmacology* ; NF-KappaB Inhibitor alpha ; Inflammation

Objective Maintain a sable differential pressure inside the Underwater Positive Pressure Protective Suit(UPPPS)to ensure normal breathing and safe underwater operations for the diver.Methods Utilize a pressure regulator as the UPPPS's pressure control valve to automatically maintain the differential pressure inside the suit.Results By establishing a physical model,the relationship between the steady-state differential pressure with the ventilation flow rate and the ambient pressure was obtained.(1)The ventilation flow rate is positively correlated with the steady-state differential pressure,the higher the ventilation flow rate,the greater the steady-state differential pressure.(2)At the same ventilation flow rate,the larger the ambient pressure is,the smaller the steady-state differential pressure is.Underwater unmanned and manned experiments using the UWT suit were conducted.The expermental results are in agreement with the theoretical analysis.Conclusion The performance of pressure regulator has been verified by the underwater experiments,it effectively stabilizes the differential pressure within the UPPPS.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Objective:To investigate the value of quantitative parameters of amide proton transfer-weighted (APTw) imaging and dynamic contrast-enhanced (DCE)-MRI for preoperative assessment of human epidermal growth factor receptor 2 (Her-2) gene expression in endometrial cancer (EC).Methods:This research conducted a diagnostic pilot study involving 68 patients with pathologically confirmed EC at the First Hospital of Dalian Medical University from August 2019 to August 2023. Patients were categorized into Her-2-positive group (33 cases) and Her-2-negative group (35 cases) based on postoperative Her-2 gene expression results. Utilizing the APTw and DCE-MRI sequences, quantitative parameters including the asymmetric magnetization transfer ratio (MTR asym) for APTw and the volumetric transfer constant (K trans), plasma volume fraction (V p), extracellular mesenchymal space (V e), and rate constant (K ep) for DCE-MRI were acquired for the lesion site. Statistical differences in the values of each quantitative parameter between the two groups were evaluated using two independent sample t test or Mann-Whitney U test. The study incorporated quantitative parameters and clinicopathological data of patients to identify independent predictors of EC Her-2 gene expression through logistic regression analysis. A diagnostic model was developed using binary logistic regression analysis. The effectiveness of the parameters and diagnostic model was evaluated using receiver operating characteristic curves. DeLong test was used to compare the differences between the areas under the curves (AUC). Results:The study found statistically significant differences in MTR asym, K trans, and V e between the Her-2-positive group and the Her-2-negative group ( Z=2.55, P=0.011; t=-2.03, P=0.047; t=-2.13, P=0.037). However, the differences in V p and K ep were not statistically significant ( Z=0.58, P=0.560; Z=0.19, P=0.849). MTR asym emerged as a significant independent predictor of Her-2 gene expression in EC ( OR=1.016, 95% CI 1.003-1.030, P=0.014). Incorporating MTR asym, K trans, and V e, the diagnostic model yielded an AUC (95% CI) of 0.745 (0.625-0.864). The AUC (95% CI) for MTR asym, K trans, and V e alone were 0.680 (0.551-0.808), 0.623 (0.485-0.760), and 0.656 (0.523-0.789) respectively. The differences in AUC between the diagnostic model and individual predictors MTR asym, K trans, and V e were not found to be statistically significant ( Z=1.40, 1.92, 1.37, P=0.163, 0.055, 0.171). Conclusion:The quantitative parameters of APTw and DCE-MRI sequences can preoperatively assess EC Her-2 gene expression from a different perspective, with MTR asym potentially serving as a valuable independent predictor.

Objective:To investigate the correlation between urinary electrolyte level and detrusor overactivity (DO) in children with primary monosymptomatic nocturnal enuresis (PMNE).Methods:In this case control study, a retrospective analysis was performed on 60 PMNE children aged 5-12 years who were admitted to the First Affiliated Hospital of Zhengzhou University from February 2015 to January 2020.According to the results of ambulatory urodynamic monitoring (AUM), there were 36 patients in the nocturnal DO group [(19 males and 17 females, mean age(9.4±2.1) years, mean body mass index (BMI)(18.90±2.66) kg/m 2], and 24 patients in the non-nocturnal DO group [16 males and 8 females, mean age(9.0±1.9) years, mean BMI(18.85±2.50) kg/m 2].Daytime and nighttime urine volume and average urine electrolyte levels were measured. t-test, Chi-square test or Mann-Whitney U test were used for comparison between groups.Spearman rating coefficient was used to evaluate the correlation between average electrolyte level and maximum detrusor pressure during nighttime bladder storage. Results:There were no statistically significant differences in age, gender ratio, and BMI between the two groups (all P>0.05).The nocturnal urine volume [0.291(0.194, 0.408) L] and the frequency of nocturnal polyuria (33.0%) in the nocturnal DO group were significantly lower than those [0.420 (0.298, 0.673) L and 62.5%](all P<0.05) in the non-nocturnal DO group.The levels of nocturnal urine sodium [(181.13±102.39) mmol/L], calcium [(3.68±2.44) mmol/L], and chloride [(147.89±57.21) mmol/L] in the nocturnal DO group were significantly higher than those [levels of nocturnal urine sodium [(132.15±67.42) mmol/L], calcium [(1.98±2.07) mmol/L], and chloride [(110.95±54.27) mmol/L] in the non-nocturnal DO group (all P<0.05).However, there was no statistically significant difference in the level of nocturnal urine potassium between the two groups ( P>0.05).The levels of diurnal urine sodium, potassium, calcium, and chloride showed no statistically significant differences between the two groups (all P>0.05).The levels of nocturnal urine sodium [(181.13±102.39) mmol/L] and calcium [(3.68±2.44) mmol/L] in the nocturnal DO group were significantly higher than the levels of diurnal urine sodium [(132.48±79.84) mmol/L] and calcium [(1.48±1.20) mmol/L](all P<0.05); however, there was no statistically significant difference in the levels of nocturnal urine potassium and chloride compared to diurnal levels (all P>0.05).In the non-nocturnal DO group, there were no statistically significant differences in the levels of diurnal and nocturnal urine sodium, potassium, calcium, and chloride (all P>0.05).Additionally, the level of nocturnal urine calcium in the nocturnal DO group was positively correlated with the maximum detrusor pressure during the bladder storage period ( r=0.501, P<0.05). Conclusions:The increased nocturnal urine sodium, calcium, and chloride levels in children with PMNE may be one of the important reasons for the occurrence of nocturnal bladder dysfunction.

This article explores the application of Professor Zhou Zhongying's"focus on the core pathogenesis"concept in the con-text of epidemic hemorrhagic fever and examines how Academician Tong Xiaolin has inherited and developed Professor Zhou's experi-ences.Influenced by Professor Zhou Zhongying's academic thoughts and considering the contemporary context,Academician Tong Xia-olin,drawing on years of clinical experience,has proposed a new set of Nineteen Pathogenic Factors.Building upon the foundation of the Nineteen Pathogenic Factors in the The Yellow Emperor's Inner Classic,this new framework enriches and expands the understanding of disease location,etiology and pathogenesis,disease classification,and pays attention to a comprehensive understanding of diseases.It emphasizes that the process of seeking the underlying mechanisms should be approached from three aspects:dynamic,state,and condition,rather than solely focusing on the immediate clinical manifestations.This comprehensive approach to understand-ing disease development offers a fresh perspective and contributes to the application of traditional Chinese Medicine in the diagnosis and treatment of modern diseases.

OBJECTIVE To evaluate the consistency between the quetiapine LC-MS/MS kit and the laboratory-built method(reference method) in the detection results of quetiapine therapeutic drug monitoring. METHODS A total of 120 remaining plasma samples were collected from patients receiving quetiapine therapeutic drug monitoring from March to October in 2021. The plasma concentration of quetiapine was detected by kit and reference method respectively. The analysis of correlations and consistency was performed by outlier analysis, linear regression and Bland-Altman method. RESULTS No outliers were detected. The linear regression equation was Y=1.018X+4.400(r=0.998), indicating a good correlation. The Bland-Altman plot analysis showed good agreement between the two measurements. CONCLUSION The detection results of quetiapine LC-MS/MS kit and reference method are in good agreement. The kit can be used for clinical quetiapine treatment drug monitoring.

Objective To explore the value of curvature value of liver surface nodularity(LSN)based on MRI in evaluating liver function in patients with liver cirrhosis.Methods A retrospective analysis was made on the patients who underwent upper abdomen MR examination at 3.0T.The normal liver function patients and cirrhosis patients were enrolled in the study and then the Child-Pugh score of the patients were calculated.The patients were divided into three groups:normal liver group,compensated cirrhosis group and decompensated cirrhosis group.The water phase imaging of 3D modified Dixon fast field echo(mDixon-FFE)sequence was copied in DICOM format.ITK software was used to manually draw the full-thickness liver edge by two observers.The curvature value of LSN was obtained by using matlab self compiled code for follow up analysis.Kruskal-Wallis H test was used to compare the curvature value between the groups.The receiver operating characteristic(ROC)curve was drawn and the area under the curve(AUC)was obtained.Spearman test was used for the correlation analysis.Results The curvature values of LSN among the normal liver,compensated cirrhosis and decompensated cirrhosis groups gradually increased(P<0.05).Comparing normal liver with compensated cirrhosis,the AUC of diagnosing compensated cirrhosis was 0.84,with the sensitivity of 72.7%and the specificity of 89.3%.Comparing compensated cirrhosis with decompensated cirrhosis,the AUC of diagnosing decompensated cirrhosis was 0.91,with the sensitivity of 80%and the specificity of 90.9%.There was a moderate positive correlation between the curvature value of LSN and liver function score in patients with cirrhosis(r=0.63,P=0.002).Conclusion The curvature value of LSN based on MRI can be used for preliminary evaluation of liver function of liver cirrhosis,with the AUC more than 0.80 and higher sensitivity and specificity.