Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

Objective To explore the number of peripheral blood regulatory T cells (Treg) in patients with chronic kidney disease (CKD) and its correlation with vascular calcification. Methods This was a single-center, cross-sectional, and observational study. Non-dialysis patients with CKD treated at Zhongshan Hospital, Fudan University from March 2021 to March 2022 were enrolled. Abdominal aortic calcification (AAC) was assessed using lateral abdominal X-ray. Number of Treg and cytokine levels were measured by flow cytometry. Logistic regression analysis was performed to evaluate the related factors for AAC in CKD patients. Results A total of 83 patients were included, aged 17–86 years, with 57 males (68.7%). The distribution of CKD stages was as follows: stage G1 in 7 patients (8.4%), stage G2 in 17 patients (20.5%), stage G3 in 21 patients (25.3%), stage G4 in 19 patients (22.9%), and stage G5 in 19 patients (22.9%). No AAC was observed in patients with stages G1 and G2, while the prevalence of AAC in patients with stages G3, G4, and G5 was 23.8%, 21.1%, and 26.3%, respectively. Compared with stage G1 patients, those with stages G3–5 showed decreased number of peripheral blood Treg and elevated levels of interleukin (IL)-6 and IL-17F (P＜0.05). The area under the receiver operating characteristic curve for number of peripheral blood Treg in predicting AAC in CKD patients was 0.766 (95%CI 0.652–0.879, P＝0.002). Logistic regression analysis showed that decreased number of Treg was related factor for AAC in CKD patients (OR＝0.957, 95%CI 0.922–0.992, P＝0.018). Conclusion As CKD progresses, number of peripheral blood Treg significantly decreases, which is correlated with AAC in CKD patients.

ObjectiveTo evaluate the clinical efficacy of Fuzheng Huaji Formula （扶正化积方） for chronic hepatitis B to reduce the incidence of liver cirrhosis and hepatocellular carcinoma. MethodsA retrospective cohort study was conducted， collecting medical records of 118 patients with chronic hepatitis B and 234 patients with hepatitis B-related cirrhosis who visited the hospital between January 1， 2014， and December 31， 2018. The use of Fuzheng Huaji Formula was designated as the exposure factor. Patients receiving antiviral treatment for hepatitis B without concurrent Fuzheng Huaji Formula therapy were included in the western medicine group， while those receiving antiviral treatment combined with Fuzheng Huaji Formula for a cumulative treatment lasting longer than 3 months were included in the combined treatment group. The follow-up observation period was five years. Kaplan-Meier survival analysis was used to assess the cumulative incidence of cirrhosis in patients with chronic hepatitis B and the cumulative incidence of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis. Univariate and multivariate Cox regression analyses were employed to examine the factors influencing the occurrence of cirrhosis and hepatocellular carcinoma. ResultsAmong patients with chronic hepatitis B， there were 55 cases in the combined treatment group and 63 cases in the western medicine group； among patients with hepatitis B-related cirrhosis， there were 110 cases in the combined treatment group and 124 cases in the western medicine group. Five-year follow-up outcomes for chronic hepatitis B patients showed that the cumulative incidence of cirrhosis was 5.45% （3/55） in the combined treatment group and 17.46% （11/63） in the western medicine group， with a statistically significant difference between groups （Z = 2.003， P = 0.045）. Five-year follow-up outcomes for hepatitis B-related cirrhosis patients showed that the cumulative incidence of hepatocellular carcinoma was 8.18% （9/110） in the combined treatment group and 22.58% （28/124） in the western medicine group， also showing a statistically significant difference （Z = 3.007， P = 0.003）. Univariate and multivariate Cox regression analyses indicated that treatment with Fuzheng Huaji Formula is an independent protective factor in preventing the progression of chronic hepatitis B to cirrhosis and the progression of hepatitis B-related cirrhosis to hepatocellular carcinoma （P＜0.05）. ConclusionCombining Fuzheng Huaji Formula with antiviral therapy for hepatitis B can effectively intervene in the disease progression of chronic hepatitis B， reducing the incidence of cirrhosis and hepatocellular carcinoma.

Objective To construct programmed cell death protein-ligand 1(PD-LI)^hi tolerogenic dendritic cell (tol-DC) derived from bone marrow of DA rats and identify its immunological function. Methods DA rat bone marrow cells were extracted, combined with recombinant mouse granulocyte macrophage colony-stimulating factor and recombinant mouse interleukin (IL)-4, and cultured for 6 days in vitro to induce the differentiation of bone marrow cells into immature dendritic cells (imDC). Lipopolysaccharide was used to stimulate cell maturation and cultured for 2 days to collect mature dendritic cells (mDC). PD-L1 lentiviral vector virus stock solution or equivalent dose lentiviral stock solution was added, and PD-L1^hitol-DC and Lv-imDC were collected after culture for 2 days. The morphology of PD-L1^hitol-DC was observed by inverted phase contrast microscope and transmission electron microscope. Real-time fluorescence quantitative reverse transcription polymerase chain reaction, Western blotting and flow cytometry were used to detect the expression level of specific markers on cell surface. CD8⁺T cells derived from Lewis rat spleen were co-cultured with imDC, mDC, Lv-imDC and PD-L1^hitol-DC, respectively. The levels of inflammatory factors in the supernatant of each group were detected by enzyme-linked immunosorbent assay. The apoptosis of T cells and the differentiation of regulatory T cells (Treg) in each group were analyzed by flow cytometry. Results The morphology of PD-L1^hitol-DC modified by PD-L1 gene was consistent with tol-DC characteristics, and the expression levels of CD80, CD86 and major histocompatibility complex (MHC) on the surface were low. After mixed culture with CD8⁺ T cells, the levels of IL-10 and transforming growth factor (TGF) -β1 in the supernatant of PD-L1^hitol-DC group were higher, the levels of tumor necrosis factor (TNF) -α and IL-17A were lower, and the apoptosis of T cells and Treg differentiation were increased. Conclusions Overexpression of PD-L1 through lentiviral vectors may successfully induce the construction of bone-marrow derived PD-L1^hitol-DC in DA rats, promote the secretion of anti-inflammatory factors and T cell apoptosis, induce the differentiation of Treg, and inhibit the immune response of allogeneic CD8⁺T cells, which provides experimental basis for the next organ transplantation immune tolerance study.

AIM: To investigate the effects of insulin-like growth factor 1(IGF-1)on the secretion of transforming growth factor β2(TGF-β2), matrix metalloproteinase 2(MMP-2)and hypoxia-inducible factor 1α(HIF-1α)in human scleral fibroblasts(HSF)and their mechanism.METHODS: The cells were cultured with IGF-1 and PI3K/AKT pathway inhibitor LY294002, respectively. CCK-8 method was used to detect cell viability and determine the optimal concentration and time of drug action. Cell migration activity was observed by cell scratch method. To determine the effects of IGF-1 on HSF cells and the regulatory role of PI3K/AKT pathway, HSF cells were divided into control group(without drugs), IGF-1(80 μg/L)group, IGF-1+LY294002(80 μg/L+5 mmol/L)group, and LY294002(5 mmol/L)group, and were cultured for 24 h; the protein expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT were detected by Western blot; the fluorescence expression of TGF-β2, MMP-2 and HIF-1α was detected by cellular immunofluorescence.RESULTS: The results of CCK-8 showed that the cell viability of the 80 μg/L IGF-1 group cultured with different concentrations of IGF-1 was the highest(all P<0.05), and the cell viability of the 80 μg/L IGF-1 group at 24 h was the highest under different culture times. Therefore, the concentration of IGF-1 was selected as 80 μg/L for 24 h. The viability of cells cultured with different concentrations of LY294002 gradually decreased from 6 h(all P<0.05). According to the IC50 value, therefore, the concentration of LY294002 was selected as 5 mmol/L for 24 h. The cell scratch results showed that compared with the control group, the cell mobility of 40 μg/L and 80 μg/L IGF-1 groups was increased(all P<0.05). Compared with the control group, cell mobility in the 2.5 and 5 mmol/L LY294002 groups was decreased(all P<0.05). Western blot results showed that compared with the control group, the protein expressions of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1+LY294002 group were decreased(all P<0.05). The results of cell immunofluorescence showed that compared with the control group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1+LY294002 group were significantly decreased(all P<0.05).CONCLUSION: IGF-1 promoted the proliferation and migration of human HSF. IGF-1 may up-regulate the expression of TGF-β2, MMP-2 and HIF-1α in HSF through the PI3K/AKT signaling pathway, and participate in the occurrence and development of myopia.

ObjectiveThe controllability changes of structural brain network were explored based on the control and brain network theory in young smokers, this may reveal that the controllability indicators can serve as a powerful factor to predict the sleep status in young smokers. MethodsFifty young smokers and 51 healthy controls from Inner Mongolia University of Science and Technology were enrolled. Diffusion tensor imaging (DTI) was used to construct structural brain network based on fractional anisotropy (FA) weight matrix. According to the control and brain network theory, the average controllability and the modal controllability were calculated. Two-sample t-test was used to compare the differences between the groups and Pearson correlation analysis to examine the correlation between significant average controllability and modal controllability with Fagerström Test of Nicotine Dependence (FTND) in young smokers. The nodes with the controllability score in the top 10% were selected as the super-controllers. Finally, we used BP neural network to predict the Pittsburgh Sleep Quality Index (PSQI) in young smokers. ResultsThe average controllability of dorsolateral superior frontal gyrus, supplementary motor area, lenticular nucleus putamen, and lenticular nucleus pallidum, and the modal controllability of orbital inferior frontal gyrus, supplementary motor area, gyrus rectus, and posterior cingulate gyrus in the young smokers’ group, were all significantly different from those of the healthy controls group (P<0.05). The average controllability of the right supplementary motor area (SMA.R) in the young smokers group was positively correlated with FTND (r=0.393 0, P=0.004 8), while modal controllability was negatively correlated with FTND (r=-0.330 1, P=0.019 2). ConclusionThe controllability of structural brain network in young smokers is abnormal. which may serve as an indicator to predict sleep condition. It may provide the imaging evidence for evaluating the cognitive function impairment in young smokers.

Background Staff in biosafety laboratories (BSL) are more likely to experience occupational burnout and other psychological issues due to their unique working environment and high job demands. However, current research in this field tends to focus on overall analyses, overlooking the internal differences within this group. Objective To explore latent profiles of occupational burnout among BSL workers and their influencing factors, providing a reference for targeted burnout interventions. Methods In 2022, cluster random sampling was used to select 8023 BSL workers in Xinjiang. Data were collected via a questionnaire survey, including a self-designed general information questionnaire, the Maslach Burnout Inventory-General Survey (MBI-GS), and the Effort-Reward Imbalance (ERI) scale, to analyze demographic characteristics, occupational burnout, and job stress status. After data cleaning, latent profile analysis (LPA) was applied to identify burnout profiles, followed by K-means clustering for verification. Logistic regression was used to analyze influencing factors with burnout profiles as the dependent variable. Results After excluding invalid questionnaires, 7924 valid questionnaires were retained, with an recovery rate of 98.77%. The LPA results indicated that occupational burnout among BSL staff was categorized into three latent profiles: a low burnout profile (2208 individuals, 27.86%), a moderate burnout profile (4636 individuals, 58.51%), and a high burnout profile (1080 individuals, 13.63%). A similar grouping was derived from K-means clustering analysis (28.71%, 53.37%, and 17.92%), and a Sankey diagram demonstrated significant overlap between the two classification results. Statistically significant differences were observed across the three latent profiles in all three dimensions of burnout: emotional exhaustion, cynicism, and reduced personal accomplishment. The final logistic regression model revealed that the influencing factors exhibited characteristics of partial overlap and partial differentiation. Among the common influencing factors, the shared protective factors included: age ≥50 years (OR_{moderate burnout}=0.42, OR_{high burnout}=0.45), monthly income of 4000-6000 RMB (OR_{moderate burnout}=0.83, OR_{high burnout}=0.71), good sleep quality (OR_{moderate burnout}=0.70, OR_{high burnout}=0.13) and very good sleep quality (OR_{moderate burnout}=0.51, OR_{high burnout}=0.12), and engaging in physical exercise ≥5 times per week (OR_{moderate burnout}=0.74, OR_{high burnout}=0.48). The protective effects were more pronounced for the high burnout profile. The common risk factors included: 21–30 years of service (OR_{moderate burnout}=1.38, OR_{high burnout}=3.00), ≥31 years of service (OR_{moderate burnout}=1.47, OR_{high burnout}=3.39), working in "other positions" (OR_{moderate burnout}=1.46, OR_{high burnout}=1.56), and occupational stress (ERI>1) (OR_{moderate burnout}=2.62, OR_{high burnout}=3.25), with the risk effects being more significant for the high burnout profile. Regarding differentiated influencing factors, protective factors exclusively associated with the moderate burnout profile included having an associate degree (OR=0.70) and engaging in physical exercise 3-4 times per week (OR=0.74). For the high burnout profile, exclusive protective factors included age 40-50 years (OR=0.56), while exclusive risk factors included having a senior professional title (OR=1.85), holding a managerial role (OR=1.78), a high number of night shifts per month (OR=2.66), and a very high number of night shifts per month (OR=3.93). Conclusion BSL workers exhibit three distinct latent burnout profiles. Occupational burnout requires greater attention, and targeted prevention and intervention strategies should be developed based on worker subtypes.

Background Some studies have suggested that exposure to multiple metals is closely linked to the development of metabolic syndrome (MS) in the populations, but the effect of aluminum exposure on MS remains unclear. Objective To analyze the prevalence and influencing factors of MS among employees with aluminum exposure in Shanxi Province. Methods Cluster sampling was employed to survey male frontline workers in an aluminum factory in Shanxi Province. Data on general demographic information, lifestyle, occupational history, medical history, and family history of chronic diseases were collected through questionnaires. The concentration of fasting blood glucose was determined using the glucose oxidase technique, and blood lipid levels were determined using the peroxidase method. Serum aluminum levels were detected using inductively coupled plasma-mass spectrometry (ICP-MS), and blood biochemical indicators were measured using the peroxidase method. Based on the China's 2020 diagnostic criteria for MS, the participants were and divided into an MS group anda non-MS group. Variables with statistical significance in univariate analysis were included to construct a logistic regression model. Results A cohort of 312 workers participated in this research, with 84 individuals diagnosed with MS, yielding a prevalence rate of 26.92%. The logistic regression model revealed that body mass index (BMI)≥24.0 kg·m⁻² (OR=1.967, 95%CI: 1.057, 3.659), alcohol consumption (OR=1.883, 95%CI: 1.063, 3.336), experiencing major life event (OR=3.886, 95%CI: 1.509, 10.008), family history of hypertension (OR=2.112, 95%CI: 1.162, 3.837), serum aluminum concentration (OR=1.024, 95%CI: 1.012, 1.035), alanine aminotransferase (ALT) level (OR=1.032, 95%CI: 1.011, 1.054), and white blood cell (WBC) count (OR=1.210, 95%CI: 1.001, 1.465) were significant influencing factors for MS. Conclusion BMI≥24.0 kg·m⁻², alcohol consumption, experiencing major life event, family history of hypertension, elevated serum aluminum concentration, increased ALT level, and elevated WBC count are risk factors for MS among occupationally aluminum-exposed workers.

Objective:To investigate the effect of β-elemene on mitochondrial structure and function of the A549 cells of non-small cell lung cancer(NSCLC),and to elucidate the mechanism of β-elemene in the treatment of NSCLC.Methods:The A549 cells at logarithmic growth stage were divided into blank control group(0 mng·L-1 β-elemene),low,medium and high doses of β-elemene groups(10,25 and 50 mg·L-1),and solvent control group(0.5％ethanol in equal volume).After treatment for 24 h,the cell activities in various groups were detected by MTT assay;the morphology changes of mitochondria in the cells in various groups was observed by transmission electron microscope;the levels of adenosine 5′-triphosphate(ATP)in the cells in various groups were detected by colorimetry;the mitochondrial membrane potential of the A549 cells in various groups were detected by JC-1 flow cytometry;mitochondrial membrane permeability transfer hole assay was used to detect the mitochondrial membrane permeabilities of the cells in various groups.Results:The MTT results showed that compared with blank control group,the cell activities in low,medium and high doses of β-elemene groups were decreased gradually(P＜0.05),while the cell activity in solvent control group had no significant change,and the difference was not significant(P＞0.05).The transmission electron microscope results showed that compared with blank control group,the mitochondria of A549 cells in low,medium and high doses ofβ-elemene groups showed swelling,vacuolation,disordered arrangement and dissolution,while the mitochondrial morphology of the A549 cells in solvent control group had no significant changes.The colorimetric method results showed that compared with blank control group,the ATP levels in the A549 cells in low,medium and high dose β-elemene groups were gradually decreased(P＜0.05),while the ATP level in the A549 cells in solvent control group had no significant change,and the difference was not significant(P＞0.05).The JC-1 flow cytometry method results showed that compared with blank control group,the mitochondrial membrane potential of the A549 cells in low,medium and high doses ofβ-elemene groups were decreased,and the percentages of the cells in Q2-4 region were increased(P＜0.05);the percentage of the A549 cells in the Q2-4 region in solvent control group had no significant change.The results of mitochondrial membrane permeability transfer hole experiment showed that compared with blank control group,the mitochondrial membrane permeabilities of the A549 cells in low,medium and high doses of β-elemene groups were increased,and the percentages of the cells in M4 region were increased(P＜0.05);the mitochondrial membrane permeability of the A549 cells and the percentage of the M4 cells in solvent control group had no significant changes,and the difference was not significant(P＞0.05).Conclusion:β-elemene can inhibit the proliferation of the A549 cells,and the mechanism may be that the mitochondrial structure of A549 cells is damaged by reducing the level of ATP and mitochondrial membrane potential,changing the mitochondrial morphology and increasing the mitochondrial membrane permeability.