Antibody-drug conjugate (ADC), a novel class of antineoplastic agents, combines tumor-specific targeting with potent cytotoxic activity. In recent years, ADC has achieved notable advances in the treatment of non-small cell lung cancer (NSCLC), particularly within therapeutic sequencing after failure of first-line therapy or the emergence of resistance. This paper will systematically review the efficacy and safety evidence of representative ADC in NSCLC, and further to discuss progress and challenges in ADC structural optimization, toxicity management, biomarker identification, and combination strategies, aiming to provide a comprehensive theoretical foundation and practical reference for clinical practice and future research.
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Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Immunoconjugates/chemistry* ; Lung Neoplasms/drug therapy* ; Drug Resistance, Neoplasm/drug effects* ; Antineoplastic Agents/chemistry*

OBJECTIVE: This study investigates the efficacy and mechanisms of Qingjie Fuzheng Granules (QFG) in inhibiting colitis-associated colorectal cancer (CAC) development via RNA sequencing (RNA-seq) and 16S ribosomal RNA (rRNA) correlation analysis. METHODS: CAC was induced in BALB/c mice using azoxymethane (AOM) and dextran sulfate sodium (DSS), and QFG was administered orally to the treatment group. The effects of QFG on CAC were evaluated using disease index, histology, and serum T-cell ratios. RNA-seq and 16S rRNA analysis assessed the transcriptome and microbiome change. Key pharmacodynamic pathways were identified by integrating these data and confirmed via Western blotting and immunofluorescence. The link between microbiota and CAC-related markers was explored using linear discriminant analysis effect size and Spearman correlation analysis. RESULTS: Long-term treatment with QFG prevented AOM/DSS-induced CAC formation, reduced levels of interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), IL-6, and interferon γ (IFN-γ), and increased CD3⁺ and CD4⁺/CD8⁺ T cells ratio, without causing hepatic or renal toxicity. A 16S rRNA analysis revealed that QFG rebalanced the Firmicutes/Bacteroidetes ratio and mitigated AOM/DSS-induced microbiota disturbances. Transcriptomics and Western blotting analysis identified the nucleotide-binding oligomerization domain-containing protein 2 (NOD2)/nuclear factor kappa-B (NF-κB) pathway as key for QFG's treatment against CAC. Furthermore, QFG decreased the abundance of Bacilli, Bacillales, Staphylococcaceae, Staphylococcus, Lactobacillales, Aerococcus, Alloprevotella, and Akkermansia, while increasing Clostridiales, Lachnospiraceae, Lachnospiraceae_NK4A136_group, Ruminococcaceae, and Muribaculaceae, which were highly correlated with CAC-related markers or NOD2/NF-κB pathway. CONCLUSION By mapping the relationships between CAC, immune responses, microbiota, and key pathways, this study clarifies the mechanism of QFG in inhibiting CAC, highlighting its potential for clinical use as preventive therapy.

Neurodegenerative disorders (NDDs) are prevalent chronic conditions characterized by progressive synaptic loss and pathological protein alterations. Increasing evidence suggested that mitochondrial quality control (MQC) serves as the key cellular process responsible for clearing misfolded proteins and impaired mitochondria. Herein, we provided a comprehensive analysis of the mechanisms through which MQC mediates the onset and progression of NDDs, emphasizing mitochondrial dynamic stability, the clearance of damaged mitochondria, and the generation of new mitochondria. In addition, traditional Chinese medicines (TCMs) and their active monomers targeting MQC in NDD treatment have been demonstrated. Consequently, we compiled the TCMs that show great potential in the treatment of NDDs by targeting MQC, aiming to offer novel insights and a scientific foundation for the use of MQC stabilizers in NDD prevention and treatment.

Objective:To investigate the efficacy of arthroscopic superior capsular reconstruction using composite autologous patch graft combined with tenodesis of the long head of the biceps tendon in the treatment of irreparable massive rotator cuff tears (IMRCT).Methods:A retrospective case series study was performed on 11 IMRCT patients who were admitted to Affiliated Fuyang Hospital of Bengbu Medical University (Fuyang People′s Hospital) from May 2020 to June 2022, including 7 males and 4 females, aged 54-74 years [(62.6±7.3)years]. All the patients were treated with arthroscopic superior capsular reconstruction using composite patch graft combined with tenodesis of the long head of the biceps tendon. The Visual Analogue Scale (VAS), Acromiohumeral Distance (AHD), Constant-Murley score and University of California Los Angeles (UCLA) score and active range of motion of the shoulder joint before, at 6 months after surgery and at the last follow-up were compared. At the last follow-up, the integrity of reconstructed superior capsule and the long head of the biceps tendon was evaluated using MRI of the shoulder joint. Postoperative complications were observed.Results:All the patients were followed up for 13-39 months [16(13, 36)months]. The VAS score, AHD, Constant-Murley score, and UCLA score were 2(2, 3)points, (9.1±1.1)mm, (56.1±5.4)points, and (19.7±2.8)points respectively at 6 months after surgery, which were all significantly improved from those before surgery [6(5, 7)points, (5.1±1.2)mm, (37.9±2.2)points, and (11.8±1.2)points] ( P<0.05). The VAS score, AHD, Constant-Murley score, and UCLA score were 0(0, 1)points, (8.4±0.9)mm, (83.6±3.8)points, and (28.2±2.3)points respectively at the last follow-up, which were all significantly improved from those before surgery ( P<0.05). At the last follow-up, the VAS score or AHD were not significantly improved from those at 6 months after surgery ( P>0.05); Constant-Murley score and UCLA score were both significantly improved from those at 6 months after surgery ( P<0.05). At 6 months after surgery, shoulder active ranges of motion in forward flexion, abduction and external rotation were (134.6±13.5)°, (124.6±18.6)° and 45(40, 50)° respectively, which were all significantly improved compared with those before surgery [(63.2±36.1)°, (65.0±23.1)°, and [30(20, 40)°] ( P<0.05). At the last follow-up, shoulder active ranges of motion in forward flexion, abduction and external rotation were (144.1±12.6)°, (139.6±15.4)° and 60(45, 65)° respectively, which were all significantly improved compared with those before surgery ( P<0.05). There were no significant differences in active range of motion of the shoulder in forward flexion, abduction and external rotation between 6 months after surgery and the last follow-up ( P>0.05). At the last follow-up, MRI revealed integrity of the reconstructed superior joint capsule and the long head of the biceps tendon in 10 patients. One patient developed resorption of the greater tuberosity and 1 showed a partial tear of the supraspinatus tendon at 1 year after surgery. Conclusion:Arthroscopic superior capsular reconstruction using composite autologous patch graft combined with tenodesis of the long head of the biceps tendon can relieve shoulder pain, decrease upward displacement of the humerus head, improve the function and range of motion of the shoulder joint, and reduce complications in the treatment of IMRCT.

ObjectiveTo investigate the effects of Guizhi Jia Longgu Mulitang on the expression difference of interleukin-10 （IL-10） and tumor necrosis factor -α （TNF-α） in related organs of insomnia rats with sensory dysfunction dominated by lung and study the mechanism of Guizhi Jia Longgu Mulitang in improving insomnia. MethodSD rats were randomly divided into the blank group， model group， western medicine group， and traditional Chinese medicine （TCM） group， with 10 rats in each group. The rats were deprived of sleep by shallow water environment method in a long platform， and the modeling lasted for 42 d. The blank group and model group were given 0.05 mL·kg^-1 normal saline by gavage， and the western medicine group and TCM group were given drugs during modeling. To be specific， the western medicine group was given 0.105 mg·kg^-1 dexzopiclone tablet by gavage， while the TCM group was given 7 600 mg·kg^-1 Guizhi Jia Longgu Mulitang by gavage， both lasting for 28 days. After successful modeling， the Morris water maze experiment was performed on the 42nd day to detect the motion and spatial memory ability of rats. The levels of IL-10 and TNF-α in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The protein expression of IL-10 and TNF-α in the lung and brain tissue of rats was detected by Western blot. The levels of IL-10 and TNF-α in the lung and brain tissue of rats were detected by immunohistochemistry. ResultCompared with the blank group， the sleep stages non-rapid eye movement ( NREM ) and rapid eye movement ( REM ) of the model group were significantly shortened （P<0.5， P<0.01）， and the wake stage was significantly increased （P<0.01）. The total time and distance of platform exploration were significantly increased （P<0.01）. In the target quadrant （the third quadrant）， the percentage of exploration time and the times of crossing the platform were significantly decreased （P<0.01）. ELISA results showed that the serum IL-10 level was significantly decreased （P<0.01）， and TNF-α level was significantly increased （P<0.01）. The results of Western blot showed that the protein expression of IL-10 in brain and lung tissue of rats was significantly decreased （P<0.01）， and the protein expression of TNF-α was significantly increased （P<0.01）. The results of immunohistochemistry showed that the expression of IL-10 in the brain and lung tissue of rats was significantly decreased （P<0.01）， and that of TNF-α was significantly increased （P<0.01）. Compared with the model group， the NREM stage and REM stage of the western medicine group and the TCM group were significantly increased （P<0.5， P<0.01）， and the wake stage was shortened （P<0.5）. The total time and distance of platform exploration were significantly decreased （P<0.01）. In the target quadrant （the third quadrant）， the percentage of exploration time and the times of crossing the platform were significantly increased （P<0.05， P<0.01）. The serum IL-10 level was significantly increased （P<0.01）， and the serum TNF-α level was significantly decreased according to the ELISA results （P<0.01）. The results of Western blot showed that the protein expression of IL-10 in brain tissue and lung tissue was significantly increased （P<0.01）， and the protein expression of TNF-α was significantly decreased （P<0.01）. The results of immunohistochemistry showed that the expression of IL-10 in brain tissue and lung tissue was significantly increased （P<0.05， P<0.01）， and the expression of TNF-α was significantly decreased （P<0.05， P<0.01）. ConclusionGuizhi Jia Longgu Mulitang can improve the expression of IL-10 and TNF-α in brain and lung tissue of insomnia rats with sensory dysfunction dominated by lung， prolong sleep time， and then improve insomnia. The mechanism may be related to improving the expression level of inflammatory factors.

Heart failure(HF)is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic burden.In addition to cardiac myocyte oxidative stress and apoptosis,which are considered mechanisms for the development of HF,alterations in cardiac energy metabolism and pathological autophagy also contribute to cardiac abnormalities and ultimately HF.Silent information regulator 1(Sirt1)and adenosine monophosphate-activated protein kinase(AMPK)are nicotinamide adenine dinucleotide(NAD+)-dependent deacetylases and phosphorylated kinases,respectively.They play similar roles in regulating some pathological processes of the heart through regulating targets such as peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α),protein 38 mitogen-activated protein kinase(p38 MAPK),peroxisome proliferator-activated receptors(PPARs),and mammalian target of rapamycin(mTOR).We summarized the synergistic effects of Sirt1 and AMPK in the heart,and listed the traditional Chinese medicine(TCM)that exhibit cardioprotective properties by modulating the Sirt1/AMPK pathway,to provide a basis for the development of Sirt1/AMPK activators or inhibitors for the treatment of HF and other cardiovascular diseases(CVDs).

Objective To explore the mechanism of Yanggan Anhun Decoction in the treatment of insomnia with liver failing in storing soul type based on network pharmacological methods;To perform animal model validation.Methods The drug components and targets of Yanggan Anhun Decoction were retrieved from TCMSP and BATMAN-TCM databases,and the targets of insomnia with liver failure store soul type were retrieved from GeneCards,NCBI and DisGeNET databases.By constructing a protein-protein interaction(PPI)network and analyzing GO and KEGG pathway enrichment,the signaling pathway of Yanggan Anxin Decoction in treating insomnia with liver failing in storing soul type was determined,and molecular docking was performed between the main active components and core targets.24 SD rats were randomly divided into normal group,model group,TCM group and Western medicine group,with 6 rats in each group.The insomnia model rats with liver failing in storing soul type were constructed by compound multi factor stimulation method,and were given drugs for 14 days.The cognitive memory ability of rats were detected by Morris water maze test;Nissl staining was used to observe the morphology and number of Nissl bodies in the hypothalamus of rats;serum IL-6 and TNF-α contents were detected by ELISA;IL-6 and TNF-α in hypothalamus and Bcl-2,Bax protein expression levels of rats were detected by immunohistochemistry.The relative expressions of p38 MAPK,p-p38 MAPK,Bcl-2,Bax proteins in the hypothalamus of rats were detected by Western blot.Results A total of 301 active components,321 potential targets and 92 key targets were obtained.Key active components such as quercetin,kaempferol,luteolin,wogonin,sebiferic acid and β-sitosterol,as well as core targets such as MAPK,IL6 and TNF were obtained after screening.The key targets mainly focused on various signaling pathways such as TNF signaling pathway,MAPK signaling pathway,PI3K-Akt signaling pathway,dopaminergic synapse,and neuroactive ligand-receptor interaction,etc.Kaempferol,quercetin,digitonin and other flavonoids had good binding activity and stability with MAPK,TNF,IL6 and showed good affinity.The results of animal experiments showed that,compared with the normal group,the cognitive memory ability of the model group decreased(P<0.05),Nissl bodies were stained shallowly,the density was lower,the cell body was shrunk and deformed,the cell nucleus was broken and dissolved,and the serum and hypothalamic IL-6,TNF-α increased(P<0.05),the expressions of p-p38 MAPK/p38 MAPK and Bax in hypothalamus increased(P<0.05),while the expressions of Bcl-2 and Bcl-2/Bax decreased(P<0.05);compared with the model group,the cognitive memory ability of the TCM group and the Western medicine group were improved,the number of Nissl bodies significantly increased,the nucleus was clear,the cell body shrinkage and deformation were improved(P<0.05),the levels of IL-6 and TNF-α in serum and hypothalamus decreased(P<0.05),while the expressions of p-p38 MAPK/p38 MAPK and Bax decreased,and the expression of Bcl-2 and Bcl-2/Bax increased(P<0.05).Conclusion Yanggan Anhun Decoction may play its effects in treating insomnia with liver failing in storing soul type by regulating MAPK,TNF,IL6,Bcl-2,Bax and other core targets,and interfering with p38MAPK signaling pathway.

Objective:To evaluate the safety and effectiveness for the treatment of totally robotic fundoplication.Methods:A retrospective analysis was conducted on the clinical data of 21 patients with gastroesophageal reflux disease (GERD) who underwent unassisted totally robotic fundoplication at the Second Department of General Surgery, Yan'an Hospital Affiliated to Kunming Medical University from Aug 2023 to Jan 2024. The postoperative outcomes were evaluated using SF-36, GERD-Q, and NRS scoring indicators.Results:All 21 patients successfully underwent the surgery. The robotic surgery time was (99±41) minutes, with precise intraoperative anatomy and insignificant blood loss of (1.7±1.4) ml. There were no intraoperative or postoperative complications, and no conversions to open surgery . Postoperative recovery of bowel function was rapid (11.71±3.33) hours, with minimal postoperative pain (NRS score of 1.67±0.48).The postoperative hospital stay was short (3.86±2.90) days, and patient satisfaction was high, SF-36 score of (80.90±1.14);The symptoms of reflux after surgery was significantly reduced.Postoperative GERD-Q score of (4.38±1.69) significantly lower than the preoperative score of (13.90±2.07).Conclusion:Totally robotic fundoplication provides clear view of intraoperative anatomical structures, rapid postoperative recovery, minimal pain, and effective anti-reflux outcomes.

Objective To investigate the effect of ultrasound-guided transverse abdominal plane block(TAPB)on pain inhibition and stress response in patients undergoing laparoscopic sleeve gastrectomy(LSG).Methods 98 cases of laparoscopic sleeve Gastrectomy patients admitted from March 2021 to October 2022 were selected as the research object,and they were randomly divided into control group(49 cases)and observation group(49 cases)by double blind method.The control group received general anesthesia,and the observation group received TAPB+general anesthesia.The postoperative pain,analgesic dosage,stress level,hemodynamics and adverse reactions of the two groups were compared.Results The dosage of sufentanil and propofol in the observation group,as well as the effective press frequency of the intravenous analgesia pump 48 hours after surgery[(232.38±29.62)μg,(328.40± 40.68)mg and(5.60±1.25)],were lower than those in the control group[(294.07±35.88)μg,(402.25±46.74)mg and(9.75±2.40)](P＜0.05).The visual analogue scale(VAS)scores for each time period of the observation group were(2.43±0.49),(2.29±0.46),(2.85±0.49),(2.41± 0.39),(2.12±0.41)and(1.82±0.32),respectivly.While,the control group were(2.95±0.46),(3.22±0.51),(3.92±0.47),(3.13±0.65),(2.83±0.57)and(2.05±0.53),respectivly.The difference between the two groups was statistically significant(P＜0.05).At the time of tracheal intubation(T2),at the end of operation(T3),and at the time of leaving the anesthesia recovery room(T4),the fluctuation range of mean arterial pressure[86.00(79.00,94.00)mmHg,87.00(80.00,90.00)mmHg and 89.00(84.00,95.00)mmHg vs 82.00(75.00,90.00)mmHg,85.00(77.00,93.00)mmHg and 87.00(80.00,97.00)mmHg],heart rate[78.00(67.00,83.00)times/min,80.00(74.00,86.00)times/min and 81.00(76.00,90.00)times/min vs 78.00(67.00,83.00)times/min,80.00(74.00,86.00)times/min and 81.00(76.00,90.00)times/min]and blood oxygen saturation[97.38(97.00,97.75)％,98.69(98.30,99.05)％and 99.16(98.80,99.35)％vs 96.54(96.15,96.80)％,98.02(97.65,98.45)％and 98.73(98.43,99.15)％]in the observation group was significantly smaller than that of the control group(P＜0.05).In the observation group,cortisol levels were(192.47 ±40.25)ng/ml,(151.34±39.62)ng/ml and(118.69±30.57)ng/ml at 6 hours,24 hours and 48 hours,respectively,while in the control group were(206.24±45.34)ng/ml,(178.24±37.58)ng/ml and(143.63±32.34)ng/ml,respectively;C-reactive protein(CRP)in the observation group were(25.24±6.29)mg/L,(20.93±5.83)mg/L and(13.61±4.29)mg/L,respectively,while in the control group were(28.13±6.92)mg/L,(23.25±5.21)mg/L and(16.38±4.35)mg/L,respectively;interleukin-6(IL-6)in the observation group were(44.87±7.95)pg/L,(38.34±6.13)pg/L and(34.27±5.32)pg/L,respectively,while in the control group were(56.43±7.23)pg/L、(42.24±6.58)pg/L、(37.66±6.03)pg/L,respectively.The difference between the two groups was statistically significant(P＜0.05).The total incidence of adverse reactions of the observation group(4.08％)was lower in than that of the control group(20.41％)(P＜0.05).Conclusion Ultrasound-guided TAPB for LSG patients has a good effect on postoperative pain suppression,can reduce the stress response of the body after surgery,and is safe.

Objectives:the purpose of this study was to systematically evaluate the clinical value of cytokines in autoimmune diseases (AID). It was a kind of complex disease, and its pathogenesis involved cytokines, autoantibodies, immune cells and other immune factors. Especially some AID, such as Adult still′s disease (AOSD) and Takayasu arteritis(TA), had no specific biomarkers at present. This study was a retrospective case-control study.Methods:the data of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8(IL-8) and interleukin-10(IL-10) in 834 AID patients from January 2019 to August 2022 were collected, and the serum levels of those cytokines in 30 healthy controls (HC) were detected at the same time. And AOSD, TA, systemic lupus erythematosus (SLE) and Behcet′s syndrome (BS) were divided into active group and inactive group. In addition, we also made a subgroup analysis of two important organs involved in SLE (kidney and nervous system). GraphPad Prism 9 and R 4.2.2 software were used. Nonparametric tests (Kruskal-Wallis H test, Mann-Whitney U test) were used to compare the differences among groups, and Dunn′s method was used to correct the false positive caused by multiple tests. Results:To compare the level of IL-6 in each group, except Behcet syndrome (BS) group and antiphospholipid syndrome (APS) group, the serum IL-6 level of AID group was higher than that of HC group, with antineutrophil cytoplasmic antibodies associated vasculitis(AAV) [3.85(2.00,8.55) pg/ml], idiopathic inflammatory myopathies(IIM) [7.80(2.50,6.50)pg/ml], IgG4-related disease(IgG4RD) [3.65(2.08,12.83) pg/ml], rheumatoid arthritis (RA) [5.50(2.20,16.10) pg/ml], SLE[4.70(2.75,16.55) pg/ml], Sj?gren syndrome(SS) [3.20(2.00,8.90) pg/ml], systemic sclerosis(SSc) [2.70(2.00,8.90) pg/ml], TA[3.40 (2.00,6.50) pg/ml], other AID diseases[4.40(2.00,11.10) pg/ml], especially AOSD [15.20(2.10, 39.20) pg/ml]. After correction, the differences were statistically significant ( P c<0.05). At the same time, the levels of serum TNF-α [7.40(5.60,10.95) pg/ml]and IL-10 [5.00(5.00, 7.58) pg/ml] in AOSD group were significantly higher than those in HC group[7.15(5.93,8.00) pg/ml,5.00(5.00,5.00) pg/ml] after correction ( P c<0.05). At the same time, the levels of serum TNF-α and IL-10 in AOSD group were higher than those in HC group. The serum levels of IL-6 and IL-8 in patients with active AOSD, BS, SLE and TA were significantly higher than those in patients without active disease (all P<0.05). In addition, the level of serum IL-8 in lupus nephritis group was significantly higher than that in non-lupus nephritis group ( P<0.05). At the same time, the serum levels of IL-6, IL-8 and TNF-α in neuropsychiatric lupus erythematosus group were significantly higher than those in non-neuropsychiatric lupus erythematosus group ( P<0.05), but there was no significant difference in IL-10 between neuropsychiatric lupus group and non-neuropsychiatric lupus erythematosus group. Conclusions:there was a close relationship between AID and cytokines. At present, the change of serum IL-6 level was the most classic one in clinical routine.