With the continuous deepening of the concept of precision diagnosis and treatment for lung cancer, how to achieve higher efficiency and accuracy in the screening, diagnosis, and treatment pathways in clinical practice has become an important issue that urgently needs to be overcome. The current clinical difficulty lies in the fact that despite continuous advancements in imaging and molecular diagnostic technologies, there are still limitations in manual efficiency and subjective experience when it comes to massive data analysis and multi-scale feature extraction. Artificial intelligence (AI), especially algorithm systems based on deep learning, is an innovative technology capable of deeply empowering medical big data. This method utilizes algorithms such as convolutional neural networks, combined with radiomics, pathomics, and multi-modal data fusion analysis, demonstrating immense potential in early precise detection and benign-malignant differentiation of pulmonary nodules, digital pathological subtype recognition and non-invasive prediction of driver genes, precise 3D surgical planning and automatic delineation of radiotherapy target volumes, as well as dynamic risk warning during follow-up. This innovative technology provides a brand-new solution for realizing intelligent and individualized lung cancer diagnosis and treatment models. This consensus, based on the latest evidence from evidence-based medicine and combined with the development trends in the AI field and real-world clinical needs, was ultimately formed by gathering the consensus opinions of multidisciplinary experts in radiology, pathology, thoracic surgery, and other fields. The main content covers the application specifications of AI in the three core scenarios of lung cancer screening, diagnosis, and treatment, the technical standards for data collection and algorithm validation, as well as the ethical and regulatory challenges faced at the current stage. It aims to clarify the applicable boundaries of AI as a clinical auxiliary decision support tool, providing scientific guidance and standardized exploration directions for peers currently engaged in or planning to carry out AI-assisted clinical diagnosis, treatment, and translation of lung cancer.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

The antidepressant activity and molecular mechanisms of Yueju Wan volatile oil were investigated. The Yueju Wan volatile oil was extracted by using supercritical CO_2. Gas chromatography-mass spectrometry(GC-MS) combined with network pharmacology identified 28 chemical constituents in Yueju Wan volatile oil, primarily terpenes and lactones. A total of 123 overlapping targets were associated with depression, including core targets of interleukin-1β(IL-1β), signal transducer and activator of transcription 3(STAT3), and caspase-3(CASP3). These targets were mainly involved in the prolactin, advanced glycation end products/receptor(AGE/RAGE), and phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) signaling pathways. A reserpine-induced depression mouse model was established to evaluate the therapeutic effects and mechanisms of Yueju Wan volatile oil. The effects of Yueju Wan volatile oil on depression-like behavior in mice were evaluated by analyzing body mass, body temperature index, tail suspension immobility time, forced swimming immobility time, and sucrose preference. Hematoxylin-eosin(HE) staining revealed neuronal protection of Yueju Wan volatile oil in the brain of mice. Enzyme-linked immunosorbent assay(ELISA) and Western blot were employed to detect the protein expression of AGEs, IL-1β, phosphorylated PI3K(p-PI3K), Akt, phosphorylated Akt(p-Akt), nuclear factor κB(NF-κB), and brain-derived neurotrophic factor(BDNF). Behavioral evaluation showed that Yueju Wan volatile oil could effectively control the decline of body mass and body temperature of depressed mice, reduce tail suspension and swimming immobility time, and enhance their preference for sucrose. Histopathological examination showed that Yueju Wan volatile oil could alleviate the neuronal damage in CA1 and dentate gyrus(DG) of the hippocampus of mice. ELISA and Western blot results showed that Yueju Wan volatile oil could significantly increase the protein expression levels of PI3K, Akt, and BDNF and significantly decrease the protein expression levels of AGEs, IL-1β, p-PI3K, p-Akt, and NF-κB in the hippocampus of mice. Furthermore, the p-PI3K/PI3K and p-Akt/Akt ratios were significantly decreased at medium and high doses. These findings suggest that the aromatherapy of Yueju Wan volatile oil can significantly improve reserpine-induced depression-like behavior in mice, which may be related to reducing the expression of neuronal membrane protein AGEs, reducing the phosphorylation levels of PI3K and Akt, inhibiting NF-κB entry into the nucleus, and alleviating the release of pro-inflammatory factors and nerve injury.
Animals ; Antidepressive Agents/chemistry* ; Mice ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/immunology* ; Oils, Volatile/chemistry* ; Male ; Drugs, Chinese Herbal/chemistry* ; Signal Transduction/drug effects* ; Depression/metabolism* ; Glycation End Products, Advanced/immunology* ; Humans

Objective To investigate the relationship between cyclin A2 (CCNA2) and the prognosis of colon cancer, and its possible mechanism from the perspective of immune infiltration. Methods We downloaded the transcriptome data of colon cancer patients from The Cancer Genome Atlas database. Clinicopathological feature analysis and survival analysis were performed based on the expression levels of CCNA2. A total of 75 specimens of colon cancer and normal tissues were collected, and the expression level of CCNA2 was analyzed using immunohistochemical methods. Multivariate analysis was conducted to explore its relationship with clinicopathological features. Gene Set Enrichment Analysis (GSEA) was used to assess the potential molecular functions of CCNA2 in colon cancer. CIBERSORT algorithm was applied to calculate the correlation between CCNA2 and immune-cell infiltration in colon cancer. Results Database and immunohistochemical analyses indicated that CCNA2 was expressed at a significantly higher level in colon cancer tissues than normal tissues (P<0.001). The overall survival, disease-specific survival, and progression-free interval were all longer in the group with high CCNA2 expression than the group with low expression (all P<0.05). In tumor tissues, the expression level of CCNA2 decreased with increased pathological and TNM stages (P<0.05). The expression level of CCNA2 in normal tissues was consistently lower than that in colon cancer tissues across all clinical stages (all P<0.001). GSEA suggested that Wnt/β-catenin, KRAS, and other signaling pathways were enriched when CCNA2 was lowly expressed. CIBERSORT analysis revealed an increase in the infiltration of immune cells such as regulatory T cells and macrophages M0 when CCNA2 expression was low. Conclusion CCNA2 is highly expressed in colon cancer and closely associated with grade of pathology and TNM stage. It may recruit regulatory T cells through the KRAS and Wnt/β-catenin pathways, thereby reducing immune-cell infiltration and promoting colon cancer progression, leading to poor prognosis.

Objective:To analyze the clinical features and risk factors for renal injury in children with antineutrophil cytoplasmic antibody (ANCA)-positive IgA vasculitis (IgAV).Methods:A case-control study was conducted. Seventy-two ANCA-positive IgAV children hospitalized at the Children′s Hospital of Chongqing Medical University from January 2017 to October 2022 were enrolled as the ANCA-positive group. Propensity score matching (1∶4) using the nearest neighbor was performed with age and gender as covariate, and 288 cases ANCA-negative IgAV children were included as the ANCA-negative group. Patients with renal injury were named ANCA-positive IgAV nephritis (IgAVN) group and ANCA-negative IgAVN group, respectively. The ANCA-positive IgAVN group was further divided into myeloperoxidase (MPO) group and proteinase 3 (PR3) group based on the type of ANCA. Clinical data including manifestations, laboratory tests, renal injury, and prognosis were collected. Comparisons between groups were performed using independent sample t-tests, Mann-Whitney U tests, χ2 tests, or Fisher′s exact tests. Kaplan-Meier curves were used to assess differences in the time to renal injury onset, and multivariate logistic regression was performed to identify independent risk factors for renal injury. Results:Among the 72 ANCA-positive IgAV children (41 males, 31 females, age of 7.7 (5.3, 11.2) years), no significant difference in age or gender was observed compared to the ANCA-negative group (both P>0.05). The ANCA-positive group had higher IgM levels, a higher incidence of recurrent rash, and shorter thrombin time (all P<0.05). Among children with renal injury, the ANCA-positive group showed significant differences in the incidence of hematuria, clinical classification, and grade A prognosis compared to the ANCA-negative group (all P<0.05), but no difference was found in the time to renal involvement onest or renal pathology (all P>0.05). The MPO group had higher rates of microscopic hematuria, gross hematuria, acute renal insufficiency, glomerular sclerosis, and grade B prognosis compared to the ANCA-negative IgAVN group (all P<0.05), with a later onset of renal involvement ( P<0.05). Elevated serum creatinine ( OR=1.08, 95% CI 1.03-1.14) and shortened thrombin time ( OR=0.71, 95% CI 0.55-0.92) were independent risk factors for renal injury in ANCA-positive IgAV children (all P<0.05). Conclusions:Children with ANCA-positive IgAV are more likely to experience recurrent rash. MPO-ANCA-positive IgAVN children have higher risks of hematuria, acute kidney injury and glomerular sclerosis, with later-onset but poorer renal prognosis compared to ANCA-negative IgAVN children. Higher serum creatinine levels and shorter thrombin time may be associated with renal injury in children with ANCA-positive IgAV.

Objective:To investigate the anatomical characteristics of the atlantoaxial joint associated with nonuniform settlement of the C 2 lateral mass (C 2LM-NUS) and its correlation with atlantoaxial osteoarthritis. Methods:A retrospective analysis was conducted on clinical and imaging data of 522 hospitalized patients (288 males, 234 females; mean age 60.8±11.2 years; range 18-83 years) who underwent CT scans of the head/neck or cervical spine at the Second Affiliated Hospital of Army Medical University between January 1, 2022 and December 31, 2022. Multiplanar reconstruction of CT data was performed to measure the settlement of the C 2 lateral mass (C 2LMS). Patients with a difference in bilateral C 2LMS (d-C 2LMS) >1.4 mm were classified into the C 2LM-NUS group (137 cases; 71 males, 66 females; mean age 63.3±11.6 years), while the normal group included 385 patients (217 males, 168 females; mean age 59.9±11.0 years). Imaging parameters of the atlantoaxial joint were measured, including the C 1, 2 coronal inclination angle (C 1, 2 CI), atlanto-dental interval (ADI), lateral atlanto-dental interval (LADI), coronal deviation angle of the odontoid (Od-CDA), and C 1, 2 relative rotation angle (C 1, 2 RRA). Osteoarthritis prevalence was recorded. A normal C 0-C 3 finite element (FE) model was constructed using CT data from a 48-year-old female in the normal group. A C 2LM-NUS FE model was developed based on anatomical differences between the C 2LM-NUS and normal groups, and stress distribution on the C 2 lateral mass articular surface was analyzed under flexion-extension, lateral bending, and axial rotation torques. Results:The C 2LM-NUS group exhibited asymmetric atlantoaxial joint morphology, with bilateral differences in C 1, 2CI and LADI of 8.5°(5.8°, 11.3°) and 0.8(0.1, 1.4) mm, respectively, significantly greater than those in the normal group [1.7°(0.8°, 2.7°) and 0.2(0.1, 0.5) mm, P<0.05]. Od-CDA and C 1, 2RRA were 3.9°(2.0°, 5.4°) and 7.2°(5.0°, 10.0°) in the C 2LM-NUS group, exceeding the normal group's values [0°(0°, 1.0°) and 0°(0°, 5.5°), P<0.05]. The prevalence of C 2LM-NUS was 37.8% in the atlantoaxial osteoarthritis group, significantly higher than in the non-osteoarthritis group (22.8%, P<0.05). Significant differences were observed in age (68.3±9.4 vs. 58.6±10.8 years), sex distribution (50/69 vs. 238/165), and C 1, 2RRA [5.6°(0°, 8.2°) vs. 3.8°(0°, 6.2°)] between the osteoarthritis and non-osteoarthritis groups ( P<0.05). After adjusting for age, sex, and C 1, 2RRA, binary logistic regression identified C 2LM-NUS as an independent risk factor for atlantoaxial osteoarthritis [ OR=2.024, 95% CI (1.300, 3.150), P<0.001]. FE analysis demonstrated a reduced C 1, 2 range of motion in the C 2LM-NUS model, with elevated stress concentrations on the settled side lateral mass during simulated flexion-extension, lateral bending, and rotation. Conclusions:The study indicated that C 2LM-NUS is associated with asymmetric anatomical changes in the atlantoaxial joint, increasing the risk of osteoarthritis. Stress concentration on the C 2 lateral mass articular surface, caused by C 2LM-NUS, is a biomechanical contributor to this heightened risk.

Objective:To clarify the safety, repair rate, durability, and risk factors for recurrent mitral regurgitation(MR) in patients with Barlow disease(BD) who total thoracoscopic minimally invasive mitral valvuloplasty(TMVP).Methods:Clinical data, mid-term and long-term outcomes of BD patients who underwent TMVP at Guangdong Provincial People's Hospital from January 2009 to June 2022 were retrospectively analyzed. Patients were divided into a group with no MR recurrence(group A) and a group with MR recurrence(group B) according to whether recurrent MR appeared in the postoperative period, and the data of the two groups of patients were compared with each other for the risk factor analysis.Results:The repair rate of TMVP was 98.4%, and no patient died perioperatively. The median follow-up time was 3.1(1.7, 5.2) years, the follow-up rate was 95.8%, and there was no patient died. As of March 2023, 112 patients developed no recurrent MR(group A), 11 patients developed recurrent MR(group B), and 2 patients in group B underwent repeated mitral valve surgery. The left atrial diameter(LAD) and left ventricular end-systolic diameter(LVESD) were higher in group B than in group A patients[LAD: (50.9±7.7)mm vs.(43.7±8.7)mm, P=0.009; LVESD: (37.1±5.5)mm vs.(33.2±4.7)mm, P=0.011], and the percentage of tendon cord rupture was higher in group B than in group A( P=0.022), while the rest of the baseline data were not statistically significant. There was no statistically significant difference between two groups in terms of the use of different surgical techniques, aortic cross-clamp time, cardiopulmonary bypass time, and operative time. Postoperative LAD, postoperative LVESD, and postoperative left ventricular end-diastolic diameter of group B patients were higher than those of group A( P<0.05). There was no statistically significant difference in perioperative and long-term complication rates between the two groups. Multifactorial Cox regression analysis revealed that advanced age( HR=1.049, 95% CI: 0.997-1.103, P=0.066) and large preoperative LVESD( HR=1.168, 95% CI: 1.053-1.295, P=0.003) were the risk factors for postoperative recurrence MR. Conclusion:Total thoracoscopic minimally invasive BD repair is safe, which has a high success rate and good long-term results. Advanced age and large preoperative LVESD are risk factors for recurrent MR in the long term.

OBJECTIVES: To investigate the effect of in vitro cultured calculus bovis (ICCB) on cerebral ischemia/reperfusion injury (CIRI) and its mechanism. METHODS: A CIRI rat model and a cell model were induced by middle cerebral artery occlusion (MCAO) in Sprague Dawley rats and oxygen glucose deprivation/reperfusion (OGD/R) in BV2 cells, respectively. The CIRI rat model was evaluated using the modified neurological severity score (mNSS), brain water content, and cerebral infarction volume after 1.5 h of ischemia followed by 72 h of reperfusion. Histopathological changes in the cortex and hippocampal CA1 region were observed with hematoxylin and eosin staining. Microglial polarization and NOD-like receptor thermal protein domain associated protein (NLRP) 3 inflammasome expression in the cortex were examined by immunofluorescence. BV2 cell viability was measured via MTT assay after treatment with ICCB and Nigericin. The expressions of NLRP3, ASC, caspase-1 proteins and inflammatory cytokines were detected with Western blotting in OGD/R treated BV2 cells (0.5 h OGD+24 h reperfusion) and in cells pretreated with Nigericin for 24 h. RESULTS: ICCB treatment significantly improved neurological function, reduced cerebral infarct volume and brain water content, and mitigated pathological damage in the cortical and hippocampal CA1 regions of rats subjected to CIRI (all P<0.05). ICCB promoted the transition of cortical microglia from M1 to M2 phenotypes and suppressed NLRP3 activation in microglial cells (all P<0.01). ICCB significantly down-regulated the expression of NLRP3, ASC, and caspase-1 proteins, and reduced the secretion of IL-18 and IL-1β in BV2 cells of OGD/R model (all P<0.01). In addition, Nigericin significantly reversed the salvage effect of ICCB on model cells (both P<0.01) and the modulation of inflammatory cytokines (P<0.05). CONCLUSIONS ICCB exerts a protective effect against CIRI by mitigating neuroinflammation, through the reduction of M1 microglial polarization, promotion of M2 conversion, and suppression of the NLRP3/ASC/caspase-1 signaling pathway.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/prevention & control* ; Microglia/metabolism* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein ; Brain Ischemia/metabolism* ; Male

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.