OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure （CRF） through the reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. METHODS Rats were randomly divided into control group， model group， Yishen paidu formula low-dose （Yishen paidu formula-L） group， Yishen paidu formula high-dose （Yishen paidu formula- H） group， Yishen paidu formula-H+pcDNA-NC group， and Yishen paidu formula-H+ pcDNA-TXNIP group， with 10 rats in each group. Except for control group， all other rats were fed a diet containing 0.5% adenine to establish a CRF model； the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein， once daily， for 8 consecutive weeks. After the last administration， the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， ROS， superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β were measured in each group. Pathological changes in renal tissue were observed， and the protein expression levels of Collagen Ⅲ， α-smooth muscle actin （α-SMA）， transforming growth factor-β1 （TGF-β1）， TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group， the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr， BUN， ROS， MDA， TNF- α， IL-6 and IL-1β， and the protein expressions of Collagen Ⅲ， α-SMA， TGF-β1， TXNIP and NLRP3 were significantly decreased， while SOD levels were significantly increased （P＜0.05）. Moreover， the changes were more pronounced in the Yishen paidu formula-H group （P＜0.05）. Compared with Yishen paidu formula-H+pcDNA-NC group， above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly （P＜0.05）. CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

BACKGROUND: Lung cancer has the highest mortality rate among all malignant tumors, and non-small cell lung cancer (NSCLC) accounts for about 80%-85% of all lung cancers. Lobectomy and lymph node dissection are one of the most important treatment methods, and lymph node dissection, as an important part, has attracted much attention. And its mode and scope of dissection may affect postoperative complications, particularly the occurrence of chronic cough. The aim of this study is to investigate the effect of lymph node dissection on postoperative chronic cough in patients with NSCLC undergoing lobectomy, and to provide clinical evidence for optimizing surgical strategy and reducing postoperative chronic cough. METHODS: A retrospective analysis was conducted on the clinical data of 365 NSCLC patients who underwent lobectomy at the First Affiliated Hospital of University of Science and Technology of China from December 2020 to December 2023. The relationship between clinical characteristics and postoperative chronic cough was analyzed. The Chinese version of the Leicester Cough Questionnaire (LCQ-MC) scores were collected from the patients at 2 time points: 1 day before surgery and 8 weeks after surgery. Patients were divided according to lymph node dissection methods, to explore the relationship between lymph node dissection and chronic cough after lobectomy. Additionally, patients were divided into chronic cough and non-chronic cough groups based on the presence of postoperative chronic cough, to investigate whether perioperative data, lymph node dissection methods, and lymph node dissection regions were influencing factors. RESULTS: Patients undergoing lobectomy were more likely to have chronic cough after surgery in the systematic lymph node dissection group than in the lymph node sampling group (P<0.05). LCQ-MC scale evaluation showed that the psychological, physiological, social and total score of the patients in systematic lymph node dissection group were significantly lower than those in lymph node sampling group (P<0.05). Multivariate analysis showed that anesthesia time, operation site, lymph node dissection method, whether to perform upper mediastinal lymph node dissection, number of upper mediastinal lymph node dissection, whether to perform lower mediastinal lymph node dissection and total number of lymph node dissection were independent risk factors for postoperative chronic cough in NSCLC patients (P<0.05). CONCLUSIONS When NSCLC patients underwent lobectomy, lymph node sampling was associated with a significantly lower risk of chronic cough than systematic lymph node dissection. Dissecting lymph nodes in the upper and lower mediastinal regions and the number of lymph nodes dissected may increase the risk of postoperative cough and reduce the quality of life of patients after surgery.
Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Male ; Female ; Lung Neoplasms/surgery* ; Middle Aged ; Cough/etiology* ; Retrospective Studies ; Lymph Node Excision/methods* ; Aged ; Chronic Disease ; Postoperative Complications/etiology* ; Adult ; Lymph Nodes/surgery* ; Pneumonectomy/adverse effects* ; Chronic Cough

Objective To explore the predictive value of lipoprotein(a) (Lp[a]) levels for major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS). Methods A total of 310 ACS patients who were hospitalized in Dalian Friendship Hospital and completed coronary angiography from August 2021 to October 2023 were included in this study. According to the level of Lp(a), the patients were divided into high Lp(a) group (＞300 mg/L, n=224) and low Lp(a) group (≤300 mg/L, n=86). All patients undergo outpatient follow-up after discharge, the occurrence of major MACE was recorded, and multivariate Cox regression analysis was performed to analyze the influencing factors of MACE in ACS patients. Results The age, C-reactive protein, total cholesterol, ApoB, proportion of multiple lesions and percutaneous coronary intervention (PCI), Gensini score of the high Lp(a) group were higher than those of the low Lp(a) group, while uric acid and LVEF were lower than those of the low Lp(a) group (all P<0.05). The median follow-up time for all ACS patients was 22 (17, 24) months, with a total of 61 patients (19.68%) experiencing MACE. The high Lp(a) group had a higher readmission rate and cumulative MACE incidence for angina compared to the low Lp(a) group (P=0.009, P=0.001). Single factor analysis showed that high Lp(a) level, diabetes, myocardial infarction, left main artery disease, multi vessel disease, PCI, age, Gensini score, LVEF, and homocysteine were significantly correlated with MACE (all P<0.05). After adjusting for multiple factors, the MACE risk in the high Lp(a) group was 3.42 times higher than that in the low Lp(a) group (HR=3.42, P=0.016). Conclusion Lp(a)＞300 mg/L is an independent risk factor for the development of MACE in patients with ACS, and can be used as a predictor for the development of MACE in patients with ACS.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To analyze the burden and trends of noncommunicable chronic disease(NCD) attributable to metabolic factors in China from 1990 to 2021.Methods:Data from the Global Burden of Diseases(GBD) 2021 database were utilized to describe changes in mortality and disability-adjusted life years(DALYs) of NCD in China from 1990 to 2021. Stratified analyses were conducted by age, sex, sociodemographic index(SDI), and related risk factors. Statistical analyses and predictions were conducted using the age-period-cohort model and the Nordpred model.Results:In 2021, the age-standardized mortality rate and age-standardized DALYs rate of NCD attributable to metabolic factors in China were 227.56 per 100 000 and 4 829.39 per 100 000, respectively. Their average annual percentage changes were -0.76%( P<0.001) and -0.77%( P<0.001). Overall, the burden decreased progressively with higher SDI levels. Analysis using the age-period-cohort model indicated reduced birth cohort and period effects for metabolic factor-attributable NCD, while age effects rose significantly. The minimum relative risk( RR) value was observed in the 15-19 age group( RR=0.01), and the maximum RR value occurred in the 95-99 age group( RR=996.86). The overall rising mortality trend indicated that age effects are the predominant driver at present. Projections estimate that by 2046, deaths from metabolic factor-attributable NCD in China will reach 8 189 563, with an age-standardized mortality rate of 236.95 per 100 000. Conclusions:China continues to face a substantial burden of NCD linked to metabolic factors, with older adults, males, and individuals with hypertension, diabetes, and prediabetes identified as key populations requiring targeted interventions.

Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

Objective:To explore the split-face phenomenon in patients with bulbar-involved amyotrophic lateral sclerosis (ALS) through clinical and electrophysiological studies.Methods:A total of 52 clinically definite and clinically probable cases of bulbar-involved ALS, diagnosed according to the World Federation of Neurology El Escorial criteria, were retrospectively collected in the Third Central Hospital of Tianjin from September 2019 to November 2022. And 58 patients with idiopathic facial nerve paralysis with onset time≤7 days who visited the Department of Neurology of the Third Central Hospital of Tianjin during the same period were collected as control group. The firm eye closure (FC) score and cheek bulge (CB) score were used to assess the clinical involvement of facial muscles (dividing into facial muscle involvement group and non-facial muscle involvement group) and the presence of the split-face phenomenon (strong eye closure and weak cheek bulging) in ALS patients. The compound muscle action potential (CMAP) amplitudes of the bilateral orbicularis oculi and orbicularis oris muscles were measured using the Nicolet EDX Viking electromyography/evoked potential system. The CMAP amplitude ratio was calculated. The facial nerve electrophysiological differences were compared between ALS patients with bulbar involvement and patients with idiopathic facial nerve paralysis. The analysis of electrophysiological data across various groups was carried out utilizing the Kruskal-Wallis H test, while pairwise comparisons between groups were executed employing the Bonferroni correction method. Additionally, a stepwise binary Logistic regression analysis was implemented to ascertain the factors associated with facial muscle involvement in patients with bulbar-involved ALS. The receiver operating characteristic (ROC) curve was used to assess the diagnostic accuracy of facial nerve electrophysiological testing in diagnosing ALS in the presence of symptoms of facial muscle involvement. Results:Among the 52 ALS patients with bulbar involvement, there were 20 cases (38.5%) with facial muscle involvements, all of which were bilateral; 16 patients (30.8%) exhibited weakness solely in the ability to puff their cheeks, 1 patient (1.9%) presented with weakness exclusively in closing the eyes, and 3 patients (5.8%) experienced weakness in both closing the eyes and puffing the cheeks. The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score of the facial muscle involvement group was lower compared to the non-facial muscle involvement group (36.90±9.20 vs 40.75±5.21, t=2.419, P=0.019), while the FC score and CB score were higher in the facial muscle involvement group [FC score: 0(0, 1) vs 0(0, 0), U=5.854, P<0.001; CB score: 4(3, 4) vs 0(0, 0), U=9.069, P<0.001], showing statistically significant differences. There was no statistically significant difference in the CMAP amplitude of the orbicularis oculi muscle between the facial muscle involvement group and the healthy side of the idiopathic facial nerve paralysis group, the affected side of the idiopathic facial nerve paralysis group, and the non-facial muscle involvement group (all P>0.05). The CMAP amplitude of the orbicularis oris muscle in the facial muscle involvement group [1 100.00 (775.00, 1 375.00) μV] was lower than that in the healthy side of the idiopathic facial nerve paralysis group [1 800.00 (1 400.00, 2 300.00) μV] and the non-facial muscle involvement group [1 555.00 (1 202.50, 1 980.00) μV], with statistically significant differences ( H=5.884, P<0.001; H=4.114, P<0.001). There was no statistically significant difference in the CMAP amplitude of the orbicularis oris muscle between the facial muscle involvement group and the affected side of the idiopathic facial nerve paralysis group ( P>0.05). The CMAP amplitude ratio of the orbicularis oculi/orbicularis oris muscles in the facial muscle involvement group [0.83(0.51, 1.14)] was higher than that in the healthy side of the idiopathic facial nerve paralysis group [0.55(0.39, 0.73)], the affected side of the idiopathic facial nerve paralysis group [0.57(0.40, 0.73)], and the non-facial muscle involvement group [0.60(0.42, 0.71)], with statistically significant differences ( H=-3.440, P=0.003; H=-3.433, P=0.004; H=-3.225, P=0.008). Logistic regression analysis revealed that the CMAP amplitude of orbicularis oris muscle ( OR=0.998,95% CI 0.997-0.999, P<0.001) and ALSFRS-R score ( OR=0.916,95% CI 0.857-0.979, P=0.010) were factors associated with facial muscle involvement in ALS patients with bulbar involvement. The ROC curve analysis results showed that the area under the curve (AUC) of the orbicularis oculi muscle CMAP was 0.629, the AUC of the orbicularis oris muscle CMAP was 0.838, and the AUC of the CMAP amplitude ratio of the orbicularis oculi/orbicularis oris muscles was 0.690 in the facial muscle involvement group. Conclusions:Patients with bulbar-involved ALS have split-face phenomenon characterized by strong eye closure and weak cheek bulging. When bulbar-involved ALS patients have symptoms of facial muscle involvement, the CMAP amplitude of the orbicularis oris muscle decreases significantly, whereas the CMAP amplitude of the orbicularis oculi muscle remains relatively stable, further illustrating the split phenomenon.

Objective:To analyze the clinical and electrophysiological characteristics of patients with sensory neuronopathies (SNN), and to evaluate the significance of electrophysiological markers in the diagnosis and assessment of disease progression.Methods:A retrospective analysis was performed to evaluate the clinical manifestations, electrophysiological characteristics, and spinal cord magnetic resonance imaging (MRI) features of 8 cases diagnosed with SNN at the Third Central Hospital of Tianjin between 2015 and 2023. The neurophysiological examination mainly included limb nerve conduction study (NCS), same core needle electrode electromyography, somatosensory evoked potential (SEP), skin sympathetic reflex (SSR), and contact heat evoked potential (CHEP).Results:Among the 8 cases with SNN, 7 cases exhibited asymmetrical onset and a non-length-dependent pattern. All the 8 cases presented with severe deep sensory ataxia, accompanied by superficial sensory abnormalities and tendon areflexia. Paraneoplastic SNN were the most prevalent etiological subtype (4 cases), all of whom presented peripheral neuropathy as the initial symptom. Among these 4 cases, malignancies were identified in 3 cases and 3 cases presented with anti-Hu antibodies. Among the remaining 4 patients, 2 cases were autoimmune and the other 2 cases were idiopathic. NCS results of the 8 cases revealed decrease or absence of sensory nerve action potential (SNAP) amplitudes, with normal sensory conduction velocities. Six cases showed abnormal SEP, including 2 cases of central damage and 4 cases of peripheral damage, 5 cases had abnormal SSR, and 2 cases exhibited abnormal CHEP. Motor nerve conduction studies were normal in all 8 cases. Six patients underwent spinal MRI, and 4 exhibited abnormal signals in dorsal columns.Conclusions:The hallmark clinical manifestation of SNN is sensory ataxia, characterized by substantial impairment of superficial sensation, typically manifesting in a non-length-dependent distribution. Beyond the widespread and significant reduction in SNAP amplitudes, SNN may also exhibit additional electrophysiological impairments, such as those observed in SEP, SSR and CHEP.SEP combined with spinal cord MRI can improve the detection rate for damages in the central sensory conduction pathway.