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.

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

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.

Objective:This study aims to investigate the alterations in m 6A methylation associated with age-related idiopathic pulmonary fibrosis(IPF). Methods:By collecting peripheral blood samples from IPF patients, we investigated the changes in m6A modification levels of total RNA and key regulatory factors in elderly IPF patients.Then, the pulmonary fibrosis models of young and old mice were constructed for verification.A total of 10 IPF patients and 10 healthy controls were selected for this study.The m 6A methylation quantitative kit was employed to assess the m 6A modification levels of total RNA.The expression levels of key m 6A methylation regulators, METTL3, METTL14, and FTO, were quantified using qRT-PCR.Additionally, thirty-two healthy male C57BL/6 mice, comprising 16 mice aged 10-12 weeks and 16 mice aged 6-7 months, were divided into four groups: young control(A), young pulmonary fibrosis(B), aged control(C), and aged pulmonary fibrosis(D), with 8 mice in each group.Mice in groups B and D were intratracheally administered bleomycin to establish a pulmonary fibrosis model, while those in groups A and C received normal saline.Twenty-eight days post-model establishment, the mice were euthanized, and lung tissues were collected for analysis.Histological evaluations were performed using hematoxylin and eosin(HE)staining, Masson staining, hydroxyproline content determination, and immunohistochemistry to assess the extent of pulmonary fibrosis.The m 6A methylation quantification kit was also utilized to measure the m 6A modification levels of total RNA in lung tissue.Furthermore, the mRNA and protein expression levels of the methyltransferase METTL3 were assessed by qRT-PCR and Western blot experiments. Results:The level of m 6A modification was significantly elevated in the aged IPF patient group(0.36±0.03)compared to the control group t=4.882( P<0.05).Furthermore, the expression of METTL3 was markedly higher in the aged IPF patients( t=6.082), while the expression of METTL14 was significantly lower t=17.58( P<0.05).In contrast, the expression level of FTO did not exhibit a significant difference.It is hypothesized that the increased m 6A modification of total RNA in aged IPF patients is closely associated with METTL3.Furthermore, the degree of lung fibrosis in aged mice was more severe than that in young mice.Immunohistochemistry results indicated that TGF-β1 expression was elevated in the lung fibrosis group, with higher levels observed in group D compared to group B( t=5.891, P<0.05), and in group C compared to group A t=4.135( P<0.05).The percentage of positive area for α-SMA was significantly greater in the lung fibrosis mouse model than in the control group t=20.08( P<0.05).The level of m 6A modification was increased in both lung fibrosis groups relative to the normal control group( P<0.05), although no significant difference was found between group D and group B. Overall, METTL3 mRNA and protein expression were upregulated in the lung fibrosis group, with expression in group D being lower than in group B( P<0.05). Conclusions:The level of m 6A modification is elevated in pulmonary fibrosis, and the expression of METTL3 is upregulated in this condition.The downregulation of METTL3 may be associated with the extent of aging, which subsequently exacerbates the progression of pulmonary fibrosis.

Objective:To evaluate the efficacy of reduction robot system combined with minimally invasive, microenvironmental protection, micro-stress shielding fixator (short for "3M fixator") for Sanders types II and III calcaneal fractures.Methods:A retrospective case series study was conducted to analyze the clinical data of 26 patients (26 feet) with calcaneal fractures admitted to Fourth Affiliated Central Hospital of Tianjin Medical University from June 2022 to June 2024, including 21 males and 5 females, aged 27-69 years [(46.5±2.5)years]. Among them, 10 patients had fractures in the left foot and 16 in the right. According to the Sanders classification, the fractures were classified as type II in 16 patients and type III in 10. All the patients were treated with the close reduction with reduction robot system combined with 3M fixator in a minimally invasive procedure. The surgical waiting time, operative duration, and fracture healing time were recorded. The length, width and height of the calcaneus, B?hler′s angle and Gissane′s angle were compared before operation and at 1, 3 months after operation. The visual analogue scale (VAS) and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score before operation and at 1, 3 months after operation and at the last follow-up were detected. The postoperative complications were recorded.Results:All the patients were followed up for 6-12 months [(9.7±1.1)months]. The surgical waiting time was 1-4 days [(2.0±0.8)days]. The operative duration was 36-66 minutes [(53.2±9.5)minutes]. All the fractures achieved primary union with a healing period of 3-4 months [(3.2±0.4)months]. At 1, 3 months after operation, the length of the calcaneus [(83.3±3.7)mm and (83.6±3.6)mm], width of the calcaneus [(44.3±5.8)mm and (44.3±5.7)mm], height of the calcaneus [(50.1±3.8)mm and (50.3±3.6)mm], B?hler′s angle [(29.8±2.9)° and (29.8±3.0)°], and Gissane angle [(121.1±6.7)° and (123.9±5.9)°] were significantly improved compared with those before operation [(79.3±4.5)mm, (53.6±4.1)mm, (46.2±3.7)mm, (18.9±3.8)°, (109.0±7.5)°, respectively] ( P<0.05), with no significant differences between those indicators at 1, 3 months after operation ( P>0.05). The VAS scores were (3.2±0.6)points, (1.9±0.5)points, and (1.6±0.3)points at 1, 3 months after operation and at the last follow-up, which were lower than (7.1±0.5)points preoperatively and decreased with the prolongation of follow-up time ( P<0.05). The AOFAS scores were (73.5±6.9)points, (90.1±4.3)points, and (92.0±3.6)points, which were higher than (32.0±4.6)points preoperatively and increased with the follow-up time ( P<0.05). One patient had lateral calcaneal pain after operation, and was alleviated after rehabilitation. No complications such as infection or nonunion were found after operation. Conclusion:The reduction robot system combined with 3M fixator for Sanders types II and III calcaneal fractures demonstrates significant clinical advantages, such as reduced surgical waiting time and operative duration, promoted fracture healing, early alleviated pain, enhanced ankle joint functional recovery, and decreased complication occurrence.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Objective:To evaluate the efficacy of eculizumab in treating hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) .Methods:This retrospective study included 11 patients who developed TA-TMA after allogeneic hematopoietic stem cell transplantation and subsequently received eculizumab treatment at Peking University People′s Hospital between June 2018 and May 2024. The incidence of TA-TMA, treatment details, and clinical outcomes were analyzed.Results:Among the 11 included patients [4 males, 7 females; median age: 29 years (range: 9-56) ], underlying diseases were severe aplastic anemia (SAA) in 5 patients, acute lymphoblastic leukemia (ALL) in 3 patients, and acute myeloid leukemia (AML) in 3 patients. The median time to TA-TMA diagnosis was 48 days post-transplantation (range: 4-213 days), and all patients met the diagnostic criteria for high-risk TA-TMA. The median interval from TA-TMA diagnosis to the initiation of eculizumab treatment was 12 days (range: 1-56 days). Patients received a median of 3 doses of eculizumab (range: 1-14). Ten of the 11 patients were assessed as having no response (NR) to eculizumab at the end of treatment or at death. One patient achieved a partial response (PR) but subsequently died after TA-TMA relapsed due to infection. At the last follow-up, all patients were either lost to follow-up or had died. The median follow-up duration was 88 days (range: 33-326 days), and the median time from TA-TMA diagnosis to the last follow-up was 31 days (range: 21-113 days) .Conclusion:Eculizumab demonstrated poor efficacy in this TA-TMA cohort. This might be attributable to the critical and complex condition of the patients, delayed initiation of eculizumab treatment, and insufficient dosage.

Objective:To prepare 89Zr-labeled anti-human podoplanin (PDPN) monoclonal antibody SZ168 and evaluate its feasibility for melanoma immunoPET imaging. Methods:89Zr-desferrioxamine (DFO)-SZ168 was prepared by conjugating p-isothiocyanatobenzyl (SCN-Bn)-DFO with SZ168 and chelating with 89Zr. Quality control analyses were conducted, including labeling rate, radiochemical purity, and in vitro stability. Melanoma mouse models were created, with experimental group ( n=3) and control group ( n=3) receiving tail vein injections of 89Zr-DFO-SZ168 and 89Zr-DFO-immunoglobulin (Ig)G solutions (3.7MBq) respectively. The experimental group underwent microPET/CT imaging at 12, 24, 48 and 72h post-injection, while the control group underwent imaging at 48h post-injection. Tumor and organ radioactivity uptake was analyzed using the ROI method. Mice were sacrificed at 7d post-injection to assess the ex vivo biodistribution of 89Zr-DFO-SZ168 and 89Zr-DFO-IgG. Independent-sample t test was used to analyze the data. Results:The pH value of the 89Zr-DFO-SZ168 solution was approximately 7.0, with a labeling rate >60%, radiochemical purity >95% after PD10 column purification, and good stability after 72h in vitro. Series microPET/CT imagings showed significant tumor visualization in tumor-bearing mice. Radioactivity uptake in tumors peaked at 48h post-injection, while the tumor was not clearly detected by 89Zr-DFO-IgG microPET/CT imaging. Ex vivo biodistribution indicated that 89Zr-DFO-SZ168 mainly accumulated in tumors, liver, and bones, with tumor uptake significantly higher than that of 89Zr-DFO-IgG ((29.36±7.29) percentage activity of injection dose per gram of tissue (%ID/g) vs (8.78±1.63) %ID/g; t=4.77, P=0.009). Immunohistochemistry of tumor specimens showed high expression of PDPN in tumor tissues. Conclusions:The probe 89Zr-DFO-SZ168 is successfully prepared, showing potential for specific molecular imaging diagnosis of melanoma. This lays a basis for developing PDPN molecular target-based immuno-PET diagnosis and integrated diagnosis and treatment for melanoma.

Objective:To evaluate the safety and efficacy of donor-purified CD34 + stem cell boosts in patients with poor hematopoietic reconstruction (PHR) after haploid hematopoietic stem cell transplantation (haplo-HSCT) for aplastic anemia (AA) . Method:A retrospective analysis was conducted on 11 patients with AA and PHR who underwent haplo-HSCT and received donor-purified CD34 + stem cell boosts at Peking University People’s Hospital. Recovery of blood cell counts, incidence of graft-versus-host disease (GVHD), and overall survival (OS) were assessed. Results:Of the 11 patients with PHR, two were diagnosed with prolonged isolated thrombocytopenia (PT), one was primary poor graft function (PGF), and eight were diagnosed with secondary PGF. The median time to PHR diagnosis was 110 days (range: 60-330 days), and the median interval from transplantation to purified CD34 + hematopoietic stem cell infusion was 194 days (range: 125-456 days). The two patients with PT achieved complete platelet recovery at 22 and 13 days after CD34 + stem cell infusion, respectively. Among the remaining nine patients with PGF, six achieved complete hematopoietic recovery, with a median absolute neutrophil count recovery time of 19 days (8-158 days), HGB recovery time of 32.5 days (range: 13-158 days), and platelet recovery time of 31.5 days (range: 7-171 days). The incidence of chronic GVHD after infusion was 18.2%, with no cases of acute GVHD observed. The OS rate was 90.9% (10/11) in the 11 patients, with a median follow-up of 614 days (range: 153-1 765 days) . Conclusion:Donor-purified CD34 + stem cell boost may be an effective therapeutic strategy for PHR in patients with AA after haplo-HSCT.