Objective To reveal the scientific output and trends in pulmonary nodules/early-stage lung cancer prediction models. Methods Publications on predictive models of pulmonary nodules/early lung cancer between January 1, 2002 and June 3, 2023 were retrieved and extracted from CNKI, Wanfang, VIP and Web of Science database. CiteSpace 6.1.R3 and VOSviewer 1.6.18 were used to analyze the hotspots and theme trends. Results A marked increase in the number of publications related to pulmonary nodules/early-stage lung cancer prediction models was observed. A total of 12581 authors from 2711 institutions in 64 countries/regions published 2139 documents in 566 academic journals in English. A total of 282 articles from 1256 authors were published in 176 journals in Chinese. The Chinese and English journals which published the most pulmonary nodules/early-stage lung cancer prediction model-related papers were Journal of Clinical Radiology and Frontiers in Oncology, respectively. Chest was the most frequently cited journal. China and the United States were the leading countries in the field of pulmonary nodules/early-stage lung cancer prediction models. The institutions represented by Fudan University had significant academic influence in the field. Analysis of keywords revealed that multi-omics, nomogram, machine learning and artificial intelligence were the current focus of research. Conclusion Over the last two decades, research on risk-prediction models for pulmonary nodules/early-stage lung cancer has attracted increasing attention. Prognosis, machine learning, artificial intelligence, nomogram, and multi-omics technologies are both current hotspots and future trends in this field. In the future, in-depth explorations using different omics should increase the sensitivity and accuracy of pulmonary nodules/early-stage lung cancer prediction models. More high-quality future studies should be conducted to validate the efficacy and safety of pulmonary nodules/early-stage lung cancer prediction models further and reduce the global burden of lung cancer.

The concept of "qi deficiency with stagnation" refers to a pathological state characterized by the depletion of primordial qi， impaired qi transformation， and the development of internal stagnation. Under the cyclic chemotherapy regimen in oncology， chemotherapy-induced myelosuppression follows a progressive pathological course from qi deficiency to increasing stagnation. This sequential evolution from mild to severe myelosuppression closely aligns with the dynamic syndrome differentiation and treatment framework of "qi deficiency with stagnation". "Qi deficiency" reflects the gradual depletion of qi， blood， and essence， while "stagnation" refers to the accumulation of phlegm， turbid dampness， and blood stasis. These two components interact reciprocally， forming a vicious cycle where deficiency leads to stagnation， and stagnation further damages the healthy qi. In the early stage of mild myelosuppression， chemotoxicity begins to accumulate in the bone marrow， leading to qi consumption， blood deficiency， yin injury， and the gradual formation of turbid phlegm and damp stagnation. In the advanced stage of severe myelosuppression， the accumulation of toxicity causes qi sinking， exhaustion of essence， and marrow depletion， along with blood stasis obstructing the collaterals. Treatment strategies should be based on syndrome differentiation， with an emphasis on assessing the severity of the condition， balancing deficiency and excess， and achieving both symptomatic relief and root cause resolution.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

ObjectiveTo observe the effect of Tongxie Yaofang on the function of tumor-related natural killer （NK） cells under chronic stress and explore the possible molecular mechanism. MethodFifty SPF-grade BABL/C male mice were randomized into normal， model， and low-， medium-， and high-dose （6.825， 13.65， and 27.3 g·kg^-1， respectively） Tongxie Yaofang groups， with 10 mice in each group. Other groups except the blank group were subjected to 7 days of chronic restraint stress， and then forced swimming and tail suspension tests were carried out to evaluate the modeling performance. After the successful modeling， rats in Tongxie Yaofang groups were administrated with low-， medium-， and high-doses of Tongxie Yaofang by gavage， while those in the other groups were administrated with normal saline by gavage. After 14 days， each group of mice was inoculated with subcutaneous colon cancer to establish the model of colon cancer under chronic stress. The pathological changes of the tumor tissue in each group of mice were observed using hematoxylin-eosin （HE） staining. The content of CD49b-positive cells in the peripheral blood and tumor tissue of mice was measured by flow cytometry. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the content of molecules associated with NK cell activation in the peripheral blood. Western blot was employed to determine the protein levels of major histocompatibility complex class Ⅰ polypeptide-related sequences A and B （MICA+MICB） and UL-16-binding protein 1 （ULBP1） in the tumor tissue. ResultCompared with the normal group， the model group showed a decrease in 5-hydroxytryptamine （5-HT） content and an increase in corticosterone （CORT） content in the serum （P<0.05）. Compared with the model group， Tongxie Yaofang increased the 5-HT content and decreased the CORT content （P<0.05， P<0.01）. Compared with the normal group， the modeling increased the tumor volume and weight （P<0.05）， while Tongxie Yaofang inhibited such increases with no statistical significance. The tumor cells in the model group presented neat arrangement， irregular shape， uneven size， obvious atypia， common nuclear division， and small necrotic area， and blood vessels were abundant surrounding the tumor cells. Compared with the model group， Tongxie Yaofang groups showed sparse arrangement of tumor cells， different degrees of patchy necrosis areas in the tumor， and karyorrhexis， dissolution， and nuclear debris in the necrotic part. Compared with the normal group， the model group showed reduced CD49b-positive cells in the peripheral blood and tumor tissue （P<0.01）. Compared with the model group， Tongxie Yaofang increased CD49b-positive cells （medium dose P<0.01， high dose P<0.05， P<0.01）. Compared with the normal group， the modeling lowered the serum levels of granzymes-B （Gzms-B）， perforin （PF）， interferon （IFN）-γ， and tumor necrosis factor （TNF）-α （P<0.05， P<0.01）. Compared with the model group， low-dose Tongxie Yaofang elevated the serum levels of PF， Gzms-B， and TNF-α （P<0.05， P<0.01）， and medium-dose Tongxie Yaofang elevated the serum levels of Gzms-B， PF， IFN-γ， and TNF-α （P<0.05， P<0.01）. In addition， high-dose Tongxie Yaofang elevated the serum levels of PF， IFN-γ， and TNF-α （P<0.01）. Compared with the normal group， the model group presented down-regulated protein level of ULBP1 （P<0.05）. Compared with the model group， low-， medium-， and high-dose Tongxie Yaofang up-regulated the protein level of ULBP1 （P<0.05， P<0.01）， and medium- and high-dose Tongxie Yaofang up-regulated the protein level of MICA+MICB （P<0.05， P<0.01）. ConclusionTongxie Yaofang may promote NK cell activation by up-regulating the expression of MICA+MICB and ULBP1， thereby delaying the progression of colon cancer under chronic stress.

ObjectiveTo explore the effect of Tongxie Yaofang on the immune microenvironment of colorectal cancer in mice under chronic stress and the underlying mechanism. MethodA total of 40 male SPF BABL/C mice were randomized into normal group， stress group， Tongxie Yaofang group （13.65 g·kg^-1）， and Tongxie Yaofang-stress group （13.65 g·kg^-1）， with 10 in each group. Chronic restraint stress was induced in mice and administration （ig） of Tongxie Yaofang began after 7 days of stress. On the 14^th day， forced swim and tail suspension tests were used to examine the behavioral changes of mice after stress and the subcutaneous colorectal tumor was implanted in each group of mice. The effect of this prescription on the body mass and tumor volume of mice was observed. After the last administration， mouse serum and tumor samples were collected. The content of T lymphocytes （CD3⁺， CD4⁺， CD8⁺， and CD4⁺/CD8⁺） in tumor was detected by immunohistochemistry and flow cytometry and levels of corticosterone （CORT） in peripheral blood， and interleukin （IL）-2， interferon-γ （IFN-γ）， IL-6， and IL-10 in the serum were determined by enzyme-linked immunosorbent assay （ELISA）. The protein expression of inhibitor of nuclear factor-κB（IκB） kinase α/β （IKKα/β）， nuclear factor-κB （NF-κB）α （IκBα）， NF-κB p65， and phosphorylated （p）-NF-κB p65 was measured by Western blot. ResultCompared with the normal group， the stress group had large tumor volume （P<0.05）， low content of CD3⁺， CD4⁺， and CD4⁺/CD8⁺ （P<0.05， P<0.01）， high content of CD8⁺， low content of T helper 1 （Th1）-secreted IFN-γ （P<0.05）， high content of T helper 2 （Th2）-secreted IL-10 （P<0.05） and CORT （P<0.05）， high protein expression of p-NF-κB p65， NF-κB p65， and IKKα/β （P<0.05）， and low protein expression of IκBα （P<0.05）. Compared with the normal group， the Tongxie Yaofang group showed slow tumor growth， high content of CD3⁺， CD4⁺， and CD4⁺/CD8⁺ （P<0.01）， low content of CD8⁺ （P<0.05）， high content of Th1-secreted IL-2 and IFN-γ （P<0.05）， low content of Th2-secreted IL-6 and IL-10 （P<0.05）， low content of CORT， low protein expression of p-NF-κB p65， NF-κB p65， and IKKα/β （P<0.05）， and high protein expression of IκBα （P<0.01）. Tongxie Yaofang-stress group demonstrated slower tumor growth， higher content of CD3⁺， CD4⁺， and CD4⁺/CD8⁺ （P<0.01）， smaller content of CD8⁺ （P<0.05）， higher content of IL-2 and IFN-γ （P<0.05）， lower content of IL-6， IL-10 （P<0.05）， and CORT （P<0.05）， lower protein expression of p-NF-κB p65， NF-κB p65， and IKKα/β （P<0.05，P<0.01）， and higher protein expression of IκBα （P<0.01） than the stress group. ConclusionTongxie Yaofang can delay the growth of colorectal cancer under chronic stress and alleviate the deterioration of the immune microenvironment， possibly by inhibiting NF-κB signaling pathway， regulating the function of T lymphocyte subsets， and thus suppressing the secretion of pro-inflammatory factors.

ObjectiveTo explore the effect and mechanism of Sishenwan-containing serum on aerobic glycolysis in human colon cancer HCT116 cells. MethodCell counting kit-8 （CCK-8） was used to detect the cell viability of colon cancer HCT116 cells after treatment with Sishenwan-containing serum （2.5%， 5%， and 10%） for 24， 48， 72 h. The concentration of lactic acid， the content of intracellular glucose， and the activity of hexokinase （HK） and fructose-6-phosphate kinase （PFK） in the cell culture medium were detected by the micro-method. The content of glucose transporter 1 （GluT1） mRNA was detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression of GluT1 and methyltransferase-like 3 （MettL3） was detected by Western blot. The expression of GluT1 in cells was detected by immunofluorescence and the level of N6-methyladenosine （m⁶A） RNA methylation was detected by colorimetry. ResultCompared with the normal serum， 2.5%， 5%， and 10% Sishenwan-containing serum had no significant effect on the viability of HCT116 cells at 24 h， while 10% Sishenwan-containing serum showed a significant inhibitory effect on the viability of HCT116 cells at 48 h （P<0.05）. Hence， 10% Sishenwan-containing serum was used in subsequent experiments， and the intervention time was 48 h. Compared with the normal serum， 10% Sishenwan-containing serum could reduce lactate production （P<0.05）， down-regulate glucose uptake （P<0.05）， and blunt the activities of HK and PFK， the key rate-limiting enzymes of glycolysis （P<0.05）. Meanwhile， 10% Sishenwan-containing serum could decrease the expression of GluT1 protein （P<0.01） and mRNA （P<0.05） and reduce the proportion of cells expressing GluT1 （P<0.01）. Compared with the normal serum， Sishenwan-containing serum also decreased the protein content of MettL3 （P<0.05） and the methylation level of m⁶A RNA （P<0.01）. ConclusionSishenwan can inhibit glycolysis in colon cancer cells， and its inhibitory mechanism may be related to reducing MettL3 overexpression， inhibiting m⁶A RNA methylation， and down-regulating GluT1 and the activities of intracellular aerobic glycolysis-related enzymes such as HK and PFK.

Objective: To analyze the epidemiological characteristics and genetic characteristics of sapovirus (SaV) in a cluster of schools in Changzhou, so as to provide a reference for the treatment of clustered vomiting and diarrhea events in schools. Methods: The epidemiological data and laboratory test data of sapovirus clusters in Changzhou from 2019 to 2022 were collected and analyzed. Partial VP1 genes of SaV positive samples were amplified and sequenced for phylogenetic analysis. Results: A total of 8 cases of clusters of SaV epidemics were reported in Changzhou City from 2019 to 2022, with 118 reported cases. The total attack rate was 1.47%, and the median of the attack number was 15. There were 6 outbreaks in kindergartens and 2 outbreaks in primary schools, which were reported in the epidemic period from September to December. The main clinical manifestations were vomiting (113 cases, 95.76 %), abdominal pain (39 cases, 33.05%), and diarrhea (16 cases, 13.56%). Among the 8 outbreaks, 17 sample strains were successfully sequenced. 5 outbreaks were GII.3 , and the other 3 outbreaks were GI.1, GI .3 and GII.2. GI and GII were the main genotypes in this area, and GII .3 was the predominant strain. Conclusion SaV is an important pathogen in the clusters of vomiting and diarrhea in schools after the transmission of norovirus. Continuous surveillance of SaV should be carried out to further understand its epidemiological characteristics and genotype distribution, so as to provide scientific basis for the prevention and control of the epidemic in schools.

Objective To observe the effect of Tongxie Yaofang-containing serum on the cell cycle and apoptosis of colon cancer HCT116 cells,and to explore its possible biological mechanism.Methods Colon cancer HCT116 cells were divided into blank group and Tongxie Yaofang-containing serum group with different concentrations.Cell proliferation and activity detection-8(CCK8)was used to detect the effect of each group on the viability of HCT116 cells at 24,48 and 72 h;Flow cytometry was used to detect the apoptosis and cycle arrest of HCT116 cells induced by different concentrations of Tongxie Yaofang-containing serum;Western blot was used to detect the protein expression level of Cell Cycle Regulatory Protein P21(P21),Cyclin B1,cyclin-dependent protein kinases-1(CDK1),B-lymphoma-2(Bcl-2),Bcl-2-related X protein(Bax),phosphatidylinositol-3-kinase(PI3K),phosphorylated phosphatidylinositol-3-kinase(p-PI3K),protein kinase B(Akt)and phosphorylated protein kinase B(p-Akt)after different concentrations of Tongxie Yaofang-containing serum intervention.Results CCK8 showed that compared with the 10%blank group,10%Tongxie Yaofang-containing serum had a significant inhibitory effect on the viability of HCT116 cells only at 48 h(P<0.01);Compared with the 20%blank group,20%Tongxie Yaofang-containing serum could inhibit the viability of HCT116 cells at 48 and 72 h(P<0.01,P<0.05),and the increase of blank serum will not inhibit the viability of HCT116 cell,so 10%blank serum and 48 h were selected as the drug control and intervention time in the subsequent experiment.Flow Cytometry showed that,compared with the blank group,10%and 20%Tongxie Yaofang-containing serum could arrest HCT116 cell cycle in G2/M phase after 48 h of intervention(P<0.01),and induce HCT116 cell apoptosis.At the same time,Western blot showed that Tongxie Yaofang-containing serum could increase the expression of P21 and Bax to varying degrees,and reduces Cyclin B1,CDK1,Bcl-2,p-PI3K,p-Akt expression(P<0.05,P<0.01).Conclusion Tongxie Yaofang can inhibit the proliferation and induce apoptosis of colon cancer HCT116 cells,and its mechanism may be related to the inhibition of PI3K/Akt signaling pathway.

ObjectiveTo observe the effect of berberine combined with evodiamine on the migration and invasion of colorectal cancer HCT116 and RKO cells and to explore the underlying mechanism. Methodcell counting kit-8 （CCK-8） assay was used to examine the proliferation of HCT116 and RKO cells treated by berberine （30 μmol·L^-1）， evodiamine （0.8 μmol·L^-1）， and combination of two （30 μmol·L^-1+0.8 μmol·L^-1）， respectively. Scratch assay and Transwell assay were employed to detect the migration and invasion of HCT116 and RKO cells treated with berberine， evodiamine， and the combination， separately. In addition， the protein expression of epithelial cadherin （E-cadherin）， neural cadherin （N-cadherin）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） in HCT116 and RKO cells treated with the berberine， evodiamine， and the combination was respectively measured by Western blot. ResultCompared with the blank group， berberine alone and evodiamine alone had no significant inhibitory effect on the proliferation， migration， and invasion of HCT116 and RKO cells， while the combination showed significant inhibition （P<0.01）. Berberine alone and evodiamine alone had no remarkable influence on the expression of PI3K， N-cadherin， and E-cadherin in HCT116 and RKO cells， but the combination significantly reduced the expression of PI3K and N-cadherin （P<0.01） and increased the expression of E-cadherin （P<0.01） in HCT116 and RKO cells. Evodiamine alone also significantly suppressed the expression of Akt protein in HCT116 and RKO cells （P<0.05）， but the suppression was weaker than that of the combination. ConclusionThe combination of berberine and evodiamine can significantly inhibit the migration and invasion of colorectal cancer HCT116 and RKO cells and the two show synergy. The mechanism is the likelihood that the combination down-regulates the expression of PI3K and Akt.

Nucleos(t)ide analogues (NAs), which are widely used as the first-line anti-hepatitis B virus (HBV) drugs in clinical practice, can effectively inhibit the replication of HBV DNA, significantly slow down disease progression in chronic hepatitis B (CHB) patients, and reduce the development of end-stage liver diseases such as liver failure and liver cancer. However, for some CHB patients receiving first-line NAs for 48 weeks or longer, serum HBV DNA is still persistently or intermittently higher than the lower detection of limit of sensitive nucleic acid detection reagents. After discussion by the authors, low-level viremia (LLV) is defined as follows: persistent LLV refers to the condition in which CHB patients, who receive entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate for ≥48 weeks, test positive for HBV DNA by two consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml; intermittent LLV refers to the condition in which patients test positive for HBV DNA intermittently by at least three consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml. For the diagnosis of LLV, the issues of poor compliance and drug-resistant mutations should be excluded. LLV might be associated with the increased risk of progression to liver fibrosis or hepatocellular carcinoma in patients with liver cirrhosis under NA treatment, but there are still controversies over whether the original treatment regimen with NAs should be changed after the onset of LLV. This article summarizes the incidence rate of LLV under NA treatment and the influence of LLV on prognosis and analyzes the possible mechanisms of the osnet of LLV, so as to provide a reference for the management of LLV in patients treated with NAs.