Surgical treatment is one of the key approaches for non-small cell lung cancer (NSCLC). Regular postoperative follow-up is crucial for early detection and timely management of tumor recurrence, metastasis, or second primary tumors. A scientifically sound and reasonable follow-up strategy not only extends patient survival but also significantly improves quality of life, thereby enhancing overall prognosis. This consensus aims to build upon the previous version by incorporating the latest clinical research advancements and refining postoperative follow-up protocols for early-stage NSCLC patients based on different treatment modalities. It provides a scientific and practical reference for clinicians involved in the postoperative follow-up management of NSCLC. By optimizing follow-up strategies, this consensus seeks to promote the standardization and normalization of lung cancer diagnosis and treatment in China, helping more patients receive high-quality care and long-term management. Additionally, the release of this consensus is expected to provide insights for related research and clinical practice both domestically and internationally, driving continuous development and innovation in the field of postoperative management for NSCLC.

ObjectiveTo investigate the effect of Naoqingtong decoction （NQT） on the kidney damage and the inflammatory factors NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain （ASC）， cysteinyl aspartate-specific proteinase-1 （Caspase-1）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in spontaneously hypertensive rats （SHRs）. MethodsTwenty-four SHRs were randomized into a model group， a low-dose （12.9 g·kg^-1·d^-1） NQT （NQT-L） group， a high-dose （25.8 g·kg^-1·d^-1） NQT group （NQT-H）， and a captopril （CTP， 20 mg·kg^-1·d^-1） group， with 6 rats in each group. In addition， 6 homozygous male Wistar-Kyoto rats were used as the control group. The control and model groups were administrated with the same amount of normal saline by gavage for 8 weeks. General behaviors of rats were observed during the intervention period， and the blood pressure was measured periodically. At the end of intervention， the body mass was weighed， and both kidneys were collected and weighed for the calculation of the renal index. Hematoxylin-eosin staining was performed to observe the pathological changes in the kidney tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the expression levels of NLRP3， ASC， Caspase-1， IL-6， and TNF-α in the kidney tissue. ResultsDuring the experiment period， the control group had normal mental status， food intake， and activity， while the model group showed thinning of hair， loss of luster， reduced activity， loss of appetite， fecal adhesion， and irritability， and some of the skin had scratches or blood scabs. The above symptoms were alleviated to different degrees after 8 weeks of NQT administration. An intelligent non-invasive sphygmomanometer was used to measure the tail artery pressure of rats， which showed that the systolic and diastolic blood pressure of rats in the model group was higher than that in the control group （P<0.01）. Compared with the model group， drug interventions lowered the systolic and diastolic blood pressure （P<0.05， P<0.01）. Compared with the control group， the model group showed severe pathological damage in the kidney tissue， which was alleviated in each drug intervention group. Compared with the control group， the model group showed up-regulated expression levels of NLRP3， ASC， Caspase-1， IL-6， and TNF-α in the kidney tissue （P<0.05， P<0.01）. Compared with the model group， the drug intervention groups showed down-regulated expression levels of NLRP3， ASC， Caspase-1， IL-6， and TNF-α in the kidney tissue （P<0.05， P<0.01）. ConclusionNQT can lower the blood pressure in SHRs by inhibiting the activation of NLRP3 inflammasomes， suppressing renal inflammation， and ameliorating hypertensive kidney damage.

BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Objective : To explore whether chrysophanol(CHR) affects macrophage polarization by promoting mitochondrial biosynthesis through AMPK/PGC-1α pathway. Methods : The molecular docking and binding ability of CHR with AMPK and PGC-1α were predicted by Autodock vina software. Human monocytes(THP-1) were induced to M0 macrophages by phorbol myristate acetate(PMA), and to M1 macrophages by lipopolysaccharide(LPS) combined with interferon-γ(IFN-γ), which were set as Control group. M1 macrophages treated with CHR were set as CHR group. M1 macrophages treated with CHR combined with AMPK inhibitor(Compound C) were set as CHR+Compound C group. The mRNA expression levels of M1 macrophage markers(iNOS, CD86) and mitochondrial biosynthesis related genes(PGC-1α, NFR-1, TFAM) were detected by Quantitative real time polymerase chain reaction(qRT-PCR). The expression level of M1 macrophage marker iNOS was detected by immunofluorescence. The protein expression levels of AMPK, p-AMPK and PGC-1α were detected by Western blot. Results : The docking results showed that the binding energies of CHR with AMPK and PGC-1α were-8.4 kcal/mol and-7.4 kcal/mol, respectively. qRT-PCR results showed that the in vitro model of M1 macrophages was successfully established. Compared with the Control group, CHR treatment significantly increased the mRNA expression of mitochondrial biosynthesis-related genes PGC-1α, NFR-1, and TFAM(P<0.001). Compared with CHR treatment group, CHR combined with Compound C treatment significantly decreased the mRNA expression levels of mitochondrial biosynthesis-related genes PGC-1α, NFR-1, and TFAM(P<0.05). Immunofluorescence results showed that CHR treatment inhibited the protein expression of iNOS compared with the Control group(P<0.001). Compared with CHR treatment group,CHR combined with Compound C treatment reversed the inhibitory effect of CHR on i NOS protein expression(P<0.05). Western blot results showed that compared with the Control group,the CHR treatment group had significant increase in the protein expression levels of p-AMPK and PGC-1α(P<0.001).Compared with CHR treatment group,CHR combined with Compound C treatment significantly decreased the protein expression levels of p-AMPK and PGC-1α(P<0.05). Conclusion Chrysophanol may inhibit macrophage polarization to M1 by activating AMPK/PGC-1α signaling pathway to promote mitochondrial biosynthesis.

Objective:To evaluate the effect of the impaction of posterior wall on the prognosis following open reduction and internal fixation for fractures of acetabular posterior wall.Methods:A retrospective study was conducted to analyze the data from the 83 patients with fracture of acetabular posterior wall who had been consecutively treated by open reduction and internal fixation at Department of Orthopaedics and Traumatology, Beijing Jishuitan Hospital from January 2017 to December 2020. The patients were divided into 2 groups based on involvement of posterior wall impaction. In the impaction group of 33 cases, there were 26 males and 7 females with an age of (47.4±11.6) years; in the non-impaction group of 50 cases, there were 43 males and 7 females with an age of (41.3±12.0) years. The quality of postoperative fracture reduction, the function of the affected hip at the last follow-up, and the complication rate during follow-up were compared between the 2 groups. Multifactorial binary logistic regression and age subgroups were used to analyze the effects of posterior wall impaction on functional outcomes.Results:The age, rate of associated injuries in other body parts, and rate of posterior wall comminution in the impaction group were significantly higher than those in the non-impaction group ( P<0.05), but there was no statistically significant difference in other general data of patients between the 2 groups ( P>0.05). All patients were followed up for (44.5±13.3) months after surgery. The rate of anatomical reduction in the non-impaction group (96.0%, 48/50) was significantly higher than that in the impaction group (57.6%, 19/33) ( P<0.05), and the good and excellent rate by the modified Merle d'Aubigné & Postel scale at the last follow-up in the non-impaction group (84.0%, 42/50) was significantly higher than that in the impaction group (51.5%, 17/33) ( P<0.05). There was no significant difference in the incidence of complications between the 2 groups ( P>0.05). After adjusting for age and gender, the difference in hip function was still significantly different between the 2 groups ( OR=0.23, 95% CI: 0.06 to 0.79, P=0.020). The effect of posterior wall impaction on functional outcomes was statistically significant in patients aged &ge;50 years ( P=0.008), whereas the difference was not statistically significant in patients aged <50 years ( P=0.194). Conclusions:Compared with non-impaction ones, acetabular fractures of posterior wall impaction tend to lead to poorer quality of reduction, which in turn affects the postoperative recovery of hip joint function. The impact of impaction fractures on functional recovery is more significant in patients aged 50 years and above.

【Objective】 To investigate the correlation of the levels of interleukin-25 (IL-25) and interleukin-33 (IL-33) in cord blood with the development of infantile eczema within 42 days after birth, so as to provide theoretical support for the prevention of early infant eczema. 【Methods】 A total of 145 newborns who met the inclusion criteria and were born in the Obstetrics and Gynecology Department of the Air Force Special Medical Center from September 2020 to September 2021 were selected. Cord venous blood was collected at birth and the levels of IL-25 and IL-33 in cord blood were measured. The occurrence and severity of infantile eczema were recorded in 42 days. 【Results】 Among 145 infants, 79(54.5%) suffered from eczema. The level of IL-25 in cord blood in eczema group was significantly lower than that in non-eczema group (Z=4.957, P<0.001), and the level of IL-33 in cord blood in eczema group was significantly higher than that in non-eczema group (Z=4.594, P<0.001). The proportion of family history of allergy in the eczema group was significantly higher than that in non-eczema group (χ²=4.693, P<0.05). Logistic regression analysis showed that family history of allergy (OR=4.296), lower level of IL-25(<14.5pg/mL) (OR=4.034) and higher level of IL-33(>21.1pg/mL) (OR=2.759) in cord blood were risk factors for eczema (P<0.05), while birth weight was not associated with the onset of eczema in infants at 42 days (P>0.05). Meanwhile, the level of IL-33 in cord blood was related to the mode of delivery (P<0.05). ROC analysis showed that the optimized positive cutoff value was <14.0pg/mL for cord blood IL-25(sensitivity 62.0%, specificity 75.8%) and >22.1pg/mL for IL-33 (sensitivity 64.6%, specificity 69.7%). Spearman correlation test found that there was a linear correlation of the level of cord blood IL-33 with eczema area and severity index (EASI) score (r=0.398, P<0.01). 【Conclusion】 Family allergy history, lower level of cord blood IL-25 and higher level of cord blood IL-33 are important influencing factors of infant eczema in 42 days after birth, and higher level of cord blood IL-33 will aggravate the severity of early infantile eczema.

Peptides are a particular molecule class with inherent attributes of some small-molecule drugs and macromolecular biologics, thereby inspiring continuous searches for peptides with therapeutic and/or agrochemical potentials. However, the success rate is decreasing, presumably because many interesting but less-abundant peptides are so scarce or labile that they are likely 'overlooked' during the characterization effort. Here, we present the biochemical characterization and druggability improvement of an unprecedented minor fungal RiPP (ribosomally synthesized and post-translationally modified peptide), named acalitide, by taking the relevant advantages of metabolomics approach and disulfide-bridged substructure which is more frequently imprinted in the marketed peptide drug molecules. Acalitide is biosynthetically unique in the macrotricyclization via two disulfide bridges and a protease (AcaB)-catalyzed lactamization of AcaA, an unprecedented precursor peptide. Such a biosynthetic logic was successfully re-edited for its sample supply renewal to facilitate the identification of the in vitro and in vivo antiparkinsonian efficacy of acalitide which was further confirmed safe and rendered brain-targetable by the liposome encapsulation strategy. Taken together, the work updates the mining strategy and biosynthetic complexity of RiPPs to unravel an antiparkinsonian drug candidate valuable for combating Parkinson's disease that is globally prevailing in an alarming manner.

Objective To enhance the standardization of surgical operations,shorten the learning curve,and reduce surgical complications by summarizing common errors and proposing solutions for beginners during pre-study of cavity construction in non-inflatable axillary approach laparoscopic thyroid surgery.Methods A retrospective analysis was made on 210 patients who underwent noninflatable axillary approach luminal thyroid surgery at the Department of Head and Neck Surgery,Zhejiang Provincial People's Hospital,between January 2022 and June 2023.Among them,150 patients were luminalized by the practitioners in the practice group,while 60 patients were luminalized by the practitioners in the skilled group.The occurrence of nine common errors during cavity construction,such as supraclavicular nerve injury and scapulohumeral muscle injury,was assessed and compared between the two groups.Results There was no statistically significant difference in age,gender,tumor diameter,tumor location or pathology type between the two groups(P＞0.05).The staff in the practice group had a significant difference in supraclavicular cutaneous nerve injury(19.33％vs.3.33％),scapulohumeral muscle injury or disarticulation(16.00％vs.0),anterior cervical band of free excess(24.00％vs.3.33％),pectoralis major muscle and supraclavicular fascia injury(16.00％vs.5.00％),external jugular vein and genuine branch injury(8.00％vs.0),excessive freeing of the sternoclavicular joint(7.33％vs.0),and incorrect entry of the sternocleidomastoid muscle gap(8.67％vs.0)were significantly higher in incidence than the employees in the skilled group(P＜0.05).There was no statistically significant difference between employees in the practice group and those in the skilled group in terms of injury to the internal jugular vein and its geniculate branches(4.00％vs.0),and incorrect entry of the anterior cervical strap muscles into the hierarchy(2.00％vs.0)(P＞0.05).Conclusion The incidence of damage to the surrounding tissue was significantly higher in the novice group than in the expert group during endoscopic thyroid surgery for space construction.A solid anatomical foundation and proficient endoscopic surgical technique serve as fundamental prerequisites for achieving a successful space system construction.By summarizing common challenges and providing corresponding solutions encountered during endoscopic thyroid surgery,this study further enhances and refines the learning system for total endoscopic thyroid procedures.