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.

Objective To analyze the risk factors for chronic cough following pulmonary surgery in patients with non-small cell lung cancer (NSCLC). Methods A retrospective analysis was conducted on 427 NSCLC patients who underwent pulmonary surgery in the Department of Thoracic Surgery, The First Affiliated Hospital of the University of Science and Technology of China, between January 2021 and June 2023. Patients were categorized into a chronic cough group (103 patients) and a non-chronic cough group (324 patients) based on the presence of cough at 8 weeks post-surgery. A comparative analysis was performed between the two groups, considering gender, age, smoking history, comorbidities, preoperative pulmonary function indicators, pleural adhesion, anesthesia duration, surgical site, operative techniques, lymph node dissection methods, tumor maximum diameter, and postoperative chest tube duration. Factors showing statistical significance in univariate analysis underwent multivariate logistic regression analysis. Results Among the 427 patients undergoing pulmonary surgery, there were 165 males and 262 females, with an average age of (59.93±12.11) years. The incidence of chronic cough was 24.12%. Univariate analysis revealed significant differences in smoking history, preoperative pulmonary function indicators, pleural adhesion, anesthesia duration ≥135.5 minutes, surgical site, operative techniques, lymph node dissection methods, tumor maximum diameter, and postoperative chest tube duration (P<0.05). Multivariate logistic regression analysis indicated that the surgical site (right upper lung), operative techniques (lobectomy), lymph node dissection, and anesthesia time ≥135.5 minutes were independent risk factors for chronic cough following pulmonary surgery. Conclusion Patients undergoing right upper lung surgery, lobectomy, lymph node dissection, and experiencing anesthesia duration ≥135.5 minutes are at a higher risk of developing chronic cough post-pulmonary surgery.

Objective:To analysis the prevalence characteristics of cancer mortality among the elderly in Qidong City, Jiangsu Province, from 1972 to 2021, and to provide scientific basis for the development of precise prevention and control strategies for cancer in the elderly.Methods:Data of cancers were obtained from Qidong Cancer Registry, a descriptive study method was used to calculate the crude mortality rate (CMR) of cancer among the elderly (≥60 years old). The China age-standardized rate (ASR-C) was calculated using the age structure of the Chinese population in 2000, and world age-standardized rate (ASR-W) was calculated using Segi's world standard population. Joinpoint regression analysis was performed using Joinpoint 4.9.1.0 software to calculate the annual percentage change (APC) and average annual percentage change (AAPC) of mortality.Results:From 1972 to 2021, there were 74 723 cancer deaths in the elderly in Qidong, with CMR of 752.08/10 5, ASR-C of 666.03/10 5 (994.22/10 5 for males and 470.29/10 5 for females) and ASR-W of 681.11/10 5. The ASR-C showed little fluctuation before 2000, increased rapidly from 2001 to 2011, and then decreased from 2011 to 2021. From 2017 to 2021, the CMR was 791.01/10 5, the ASR-C was 689.80/10 5 (956.77/10 5 for males and 469.98/10 5 for females), and the ASR-W was 657.53 /10 5. The CMR for the 60-64, 65-69, 70-74, 75-79, and 80+ age groups from 2012 to 2021 were 385.42/10 5 505.51/10 5, 721.64/10 5, 1 213.28/10 5, and 1 705.32/10 5, respectively. The CMR of elderly under 75 years old were lower from 2012 to 2021 than in other periods, while those of elderly people aged more than 75 years were higher from 2012 to 2021 than in other periods. The AAPC for ASR-C of all cancers over the 50 years was 0.22%, with APC of -1.59% in 2008-2021 (both P＜0.05). Over the 50 years, the top five cancers in terms of mortality were lung cancer, gastric cancer, liver cancer, colorectal cancer, and esophageal cancer. Their AAPCs of ASR-C were 1.61%, -2.36%, -0.10%, 1.44%, and -2.03%, respectively. The increasing trends of mortality rates for lung cancer and colorectal cancer and the decreasing trends for gastric cancer and esophageal cancer were statistically significant ( P＜0.05). Conclusions:The mortality of cancers among elderly is at a high level in Qidong. The overall mortality since 2008 have shown a decreasing trend, and the prevention and control of some cancers have been effective.

Objective To explore the value of MRI subtraction technique(ST)for evaluating the efficacy of systemic therapy for advanced hepatocellular carcinoma(HCC)and predicting prognosis after combining with surgery.Methods Totally 35 patients with 39 HCC lesions who received systemic therapy+radical resection were retrospectively collected.Based on preoperative MRI,tumor activity ratio(recorded as tumor activityST)was obtained with ST,while tumor activity value(recorded as tumor activitypathology)was obtained through postoperative pathology,and their correlation was analyzed.The patients were regularly followed up after surgery,and the survival data were recorded.Receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of tumor activityST for predicting patients'survival status.Then the patients were divided into survival benefit group and no survival benefit group according to the cut-off value,and survival analysis was conducted.Results Tumor activityST was positively correlated with tumor activitypathology(r=0.900,P＜0.001).The median follow-up time was 32.93 months,during which 8 patients died,and the median survival time was 29.9 months.The area under the curve(AUC)of tumor activityST for predicting patients'survival status was 0.67,and the cut-off value was 0.36.Thirty patients with tumor activityST＜0.36 were enrolled in survival benefit group,while 5 patients≥0.36 were collected in no survival benefit group.The overall survival in survival benefit group was longer than that in no survival benefit group(P＜0.001).Conclusion MRI ST could be used to non-invasively evaluate the efficacy of systemic therapy for advanced HCC and predict prognosis after combining with surgery.

Psoriasis, a chronic, immune-mediated inflammatory disease characterized by hyperproliferation of keratinocytes, is difficult to cure and prone to relapse, often leading to systemic damage. Triptolide (TPL) can modulate cutaneous immune responses and inflammation, yet its therapeutic window is narrow with significant toxicity. To enhance skin targeting and retention of TPL while reducing systemic absorption and toxicity, a TPL/hyaluronic acid/phospholipid polymeric micelle (TPL/HA-DOPE) was constructed via HA's targeting of the CD44 receptor on skin cells. The prepared TPL/HA-DOPE exhibited a uniform spherical morphology with particle size of (130.4±1.23) nm, drug loading capacity of (19.74±0.084) %, and encapsulation efficiency of (85.53±1.34) %. Transdermal permeation studies in vitro and in vivo demonstrated that TPL/HA-DOPE not only enhanced uptake in HaCaT cells but also exhibited excellent skin retention. In a murine model of psoriasis, the TPL/HA-DOPE gel at the dose of 50 μg/(kg•d) showed the most significant improvement in erythema, scaling, and epidermal thickening. Histological analysis confirmed that TPL/HA-DOPE markedly reduced stratum corneum thickness, epidermal hyperplasia, and inflammatory cell infiltration. Ki67 immunostaining proved that its anti-inflammatory mechanism might be achieved by reducing the number of Ki67-positive cells and lowering the levels of inflammatory factors IL-6 and TNF-α. The above results demonstrate that HA-DOPE as a drug delivery carrier for the treatment of psoriasis-like skin diseases has high value of scientific research and good prospects for clinical application.

Objective To investigate the effect of β-arrestin1(ARRB1)on cell proliferation,migration and invasion in oral squamous cell carcinoma(OSCC).Methods Based on The Cancer Genome Atlas(TCGA)database,the expression profiles of ARRB1 in OSCC were analyzed,and then Gene Set Enrichment Analysis(GSEA)was used to suggest the possible signaling pathways involved,and to explore its potential impact on the prognosis of OSCC patients.Immuinohistochemistry(IHC)was performed to detect the expression of ARRB1 in OSCC tumor tissues and adjacent tissues,and the correlation between ARRB1 expression and clinicopathological features was statistically analyzed.The expression profiles of ARRB1 in SCC-15,CAL-27 and HOK cell lines were verified by qPCR and Western blotting.The ARRB1 overexpression plasmid model was constructed,and its effects on the proliferation,migration and invasion of OSCC cells were analyzed by clone formation,EdU,scratch and Transwell assays.Results TCGA showed that the expression level of ARRB1 was significantly lower in head and neck squamous cell carcinoma(HNSC)and OSCC tissues than the corresponding normal tissues(P<0.01).The expression of ARRB1 in OSCC tissues was correlated with tumor differentiation,lymph node metastasis and TNM stage(P<0.05).The OSCC patients with high expression of ARRB1 had a lower survival rate than those with low expression(P<0.01),which was consistent with the results of bioinformatics analysis.The expression level of ARRB1 in SCC-15 and CAL-27 cells was lower than that of HOK cells(P<0.01),and its overexpression significantly inhibited cell proliferation(P<0.05),migration(P<0.01)and invasion(P<0.01).Conclusion ARRB1 is lowly expressed in OSCC,its overexpression inhibits the proliferation,migration and invasion of OSCC cells,and it is related to prognosis improvement.

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 diagnostic value of combined detection of microRNA(miRNA)and alpha-fetoprotein(AFP),protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ)in ascites and serum ex-tracellular vesicles(EVs)for hepatitis B virus(HBV)-related primary hepatocellular carcinoma(HCC).METHODS From Nov.2023 to Nov.2024,41 patients with liver cancer and 26 patients with liver cirrhosis who underwent ascites placement or ascites concentration and reinfusion procedures at the Fifth Medical Center of Chi-nese PLA General Hospital were selected as study subjects.Ascites and serum samples were collected.Real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to detect the expression levels of miR-21,miR-125a,miR-150 and miR-200a in EVs.Chemiluminescence was used to measure the levels of AFP and PIVKA-Ⅱ in ascites,serum and EVs from ascites and serum.An artificial neural network was utilized to con-struct a combined diagnostic model of serum and ascites markers.RESULTS The area under the curve(AUC)for distinguishing HCC from liver cirrhosis using a combination of serum and other indicators was 0.933.The AUC for distinguishing HCC from liver cirrhosis using a combination of ascites and other indicators was 0.912.By screening all detected indicators using an artificial neural network and incorporating indicators with a relative im-portance＞0.5 into the diagnostic model,the model included four indicators:ascites AFP,ascites EVs miR-21,ascites EVs miR-200a and serum EVs miR-200a.This model had a sensitivity of 80.77％,a specificity of 87.80％and an AUC of 0.960 for distinguishing HCC from liver cirrhosis patients.CONCLUSION The combined diagnos-tic markers of miRNA,AFP and PIVKA-Ⅱ in ascites and serum-derived EVs have good application value in the diagnosis of HCC.

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.