ObjectiveTo explore the antioxidant and anti-human cervical cancer HeLa cell effect and mechanisms of Andrographis paniculata polysaccharide （APP）. MethodCell function assays were conducted to assess the effects of APP （400， 450， 500 mg·L^-1） on the proliferation， migration， and invasion of HeLa cells using the cell counting kit-8 （CCK-8） assay， scratch assay， and Transwell assay. Molecular mechanism experiments were conducted to detect the effects of APP on HeLa cell apoptosis and cell cycle-related mRNA and protein expression using flow cytometry， real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR）， and Western blot analysis. The antioxidant activity of APP was tested using DPPH⁺， OH^-， and reducing power assays. ResultCompared with the blank group， APP （400， 450， 500 mg·L^-1） significantly inhibited the migration， proliferation， and invasion abilities of HeLa cells in a time- and dose-dependent manner （P<0.05， P<0.01）. Flow cytometry with propidium iodide （PI） single staining was used to detect cell cycle. The results showed that compared with the blank group， the proportion of HeLa cells in the G₂/M phase increased after 48 hours of treatment with APP （400， 450， 500 mg·L^-1）， indicating that APP can arrest HeLa cells in the G₂/M phase. Flow cytometry with fluorescein isothiocyanate （Annexin V-FITC）/PI apoptosis kit was used to detect cell apoptosis. Compared with the blank group， the proportion of early and late apoptotic HeLa cells increased in a dose-dependent manner after 48 hours of APP （400， 450， 500 mg·L^-1） treatment （P<0.05， P<0.01）， indicating that APP promotes HeLa cell apoptosis. The results of Real-time PCR and Western blot assay showed that compared with the blank group， after 48 hours of APP （400， 450， 500 mg·L^-1） treatment resulted in decreased mRNA and protein expression of cell cycle-dependent kinase-1 （CDK-1）， Cyclin B₁， and B-cell lymphoma-2 （Bcl-2）， and increased mRNA and protein expression of cysteine aspartate protease （Caspase）-3， Caspase-8， Caspase-9， and Bcl-2-associated X protein （Bax） （P<0.05， P<0.01）. These findings were consistent with the flow cytometry results and showed a dose-dependent effect. In vitro antioxidant tests demonstrated that different concentrations of APP （50-1 000 mg·L^-1） were able to scavenge DPPH⁺ and OH^- radicals， indicating certain antioxidant activity. ConclusionAPP possesses antioxidant activity and can inhibit the viability of HeLa cells while promoting their apoptosis.

Objective:To investigate the effects of long-term exposure to chrysotile and crocidolite on miRNAs and epithelial mesenchymal transformation (EMT) -related gene expression in human pleural mesothelial cells.Methods:In November 2020, fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of EMT-related genes in human pleural mesothelioma cells (NCl-H2052 cells, NCl-H2452 cells) and human normal mesothelial cells (Met-5A cells). MiRNAs with abnormal expression in human pleural mesothelioma cells were screened out from the previous miRNA chip data of research group, and target genes of differentially expressed miRNAs were predicted using miRWalk database (http: //mirwalk.umm.uni-heidelberg.de). RT-qPCR was used to verify the abnormal expression of EMT-related miRNAs in cell lines. Met-5A cells were treated with 5μg/cm 2 chrysotile and crocidolite respectively for 48 h a time, once a week and a total of 10 times. Chrysotile group, crocidolite group and control group were set up. And the control group was added with the same volume of PBS. The expression changes of EMT-related genes and abnormal expression miRNAs in each group were detected by RT-qPCR. The differences among the groups were compared by one-way ANOVA, and the differences between the control group and the experimental group were compared by dunnet- t test. Results:Compared with Met-5A cells, the expression levels of Vimentin and Twist genes were increased, and the expression level of E-cadherin genes was decreased in NCl-H2052 cells and NCl-H2452 cells ( P<0.001). Target genes of miRNAs with abnormal expression in miRNA chip were predicted, and the results showed four abnormally expressed miRNAs associated with EMT and verified the expression of these four miRNAs in the cell lines. Compared with Met-5A cells, the expression level of hsa-miR-155-5p was increased in NCl-H2052 cells and NCl-H2452 cells, the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased in NCl-H2052 cells and NCl-H2452 cells ( P<0.001), which was consistent with the results of chip analysis. After exposure of Met-5A cells, it was found that compared with the control group, the expression levels of Vimentin and Twist genes, hsa-miR-155-5p, hsa-miR-34b-5p and hsa-miR-34c-5p in the crocidolite group were increased, while the expression level of E-cadherin gene was decreased ( P<0.05). Compared with the control group, the expression levels of Vimentin, Twist and E-cadherin genes in chrysotile group were increased, while the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased ( P<0.05) . Conclusion:Long-term exposure to chrysotile and crocidolite could cause Met-5A cells to produce miRNAs and EMT-related gene expression changes similar to mesothelioma cells.

Narrative medicine,as an interdisciplinary field at the intersection of humanistic education and medical edu-cation,is an effective means of implementing medical humanities.It not only fosters deeper empathy and communication between doctors and patients but also plays an important role in clinical practice and the cultivation of humanistic qualities.This study starts from the core connotation of integrating narrative medicine into the doctor-patient relationship,focusing on the value logic of narrative medicine empowering humanistic care.Utilizing a typical case from a hospital in Tianjin that practices humanistic care based on narrative medicine,the study examines the organizational structure,practical activities,humanistic care initiatives,health education,supportive measures,and outcomes of the narrative medicine healthcare management team.The conclusion drawn is that exploring mechanisms for medical communication and the cultivation of humanistic qualities can facilitate the mutual transformation of narrative and empathy skills,the organic combination of narrative medicine with evidence-based medicine,and the complementary relationship between clinical medicine and humanistic education.This approach aims to alleviate the increas-ingly prominent conflicts between doctors and patients,bridge the gap between humanity and technology,and promote the imple-mentation of medical humanities in clinical settings.

Objective:To investigate the effects of long-term exposure to chrysotile and crocidolite on miRNAs and epithelial mesenchymal transformation (EMT) -related gene expression in human pleural mesothelial cells.Methods:In November 2020, fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of EMT-related genes in human pleural mesothelioma cells (NCl-H2052 cells, NCl-H2452 cells) and human normal mesothelial cells (Met-5A cells). MiRNAs with abnormal expression in human pleural mesothelioma cells were screened out from the previous miRNA chip data of research group, and target genes of differentially expressed miRNAs were predicted using miRWalk database (http: //mirwalk.umm.uni-heidelberg.de). RT-qPCR was used to verify the abnormal expression of EMT-related miRNAs in cell lines. Met-5A cells were treated with 5μg/cm 2 chrysotile and crocidolite respectively for 48 h a time, once a week and a total of 10 times. Chrysotile group, crocidolite group and control group were set up. And the control group was added with the same volume of PBS. The expression changes of EMT-related genes and abnormal expression miRNAs in each group were detected by RT-qPCR. The differences among the groups were compared by one-way ANOVA, and the differences between the control group and the experimental group were compared by dunnet- t test. Results:Compared with Met-5A cells, the expression levels of Vimentin and Twist genes were increased, and the expression level of E-cadherin genes was decreased in NCl-H2052 cells and NCl-H2452 cells ( P<0.001). Target genes of miRNAs with abnormal expression in miRNA chip were predicted, and the results showed four abnormally expressed miRNAs associated with EMT and verified the expression of these four miRNAs in the cell lines. Compared with Met-5A cells, the expression level of hsa-miR-155-5p was increased in NCl-H2052 cells and NCl-H2452 cells, the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased in NCl-H2052 cells and NCl-H2452 cells ( P<0.001), which was consistent with the results of chip analysis. After exposure of Met-5A cells, it was found that compared with the control group, the expression levels of Vimentin and Twist genes, hsa-miR-155-5p, hsa-miR-34b-5p and hsa-miR-34c-5p in the crocidolite group were increased, while the expression level of E-cadherin gene was decreased ( P<0.05). Compared with the control group, the expression levels of Vimentin, Twist and E-cadherin genes in chrysotile group were increased, while the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased ( P<0.05) . Conclusion:Long-term exposure to chrysotile and crocidolite could cause Met-5A cells to produce miRNAs and EMT-related gene expression changes similar to mesothelioma cells.

Objective:To investigate the incidence and prothrombotic risk factors of postoperative venous thromboembolism(VTE) in Cushing′s disease and to further develop an assessment model to identify those at high risk of postoperative VTE events.Methods:A retrospective study was performed in 82 patients who were admitted to Huashan Hospital, Fudan University during January 2019 and January 2020 and diagnosed with Cushing′s disease. These patients underwent the evaluation about their clinical, hormonal, and coagulation parameters, as well as ultrasonography and pulmonary angio-CT when necessary. The least absolute shrinkage and selection operator(LASSO) regression analysis was used to screen independent risk factors, and a nomogram model for postsurgical VTE risk assessment in Cushing′s disease was initially established, and Bootstrap method was used for internal verification. Finally, the predictive model was evaluated for calibration and clinical applicability in the study cohort.Results:Nineteen patients(23.17%) developed VTE events, with 14 cases occurring after endoscopic transsphenoidal surgery. Compared to patients without VTE, those in the VTE group were older( P<0.001), had longer postoperative bed rest, higher rates of current infection, higher HbA 1C levels, and more severe glucose tolerance impairment(all P<0.05). Through LASSO regression analysis, two independent risk factors for postoperative VTE were identified: Age and current infection. Then a VTE risk assessment nomogram model was established to predict the patients at high risk of VTE. In the nomogram model for VTE risk assessment, the area under the receiver operating characteristic curve was 0.868(95% CI 0.787-0.949), with the calibration curve closely aligning with the ideal diagonal line and the clinical decision curve exceeding the two extreme curves. Conclusions:Advanced perioperative assessment needs to be taken to screen those with high VTE risks in patients diagnosed with Cushing′s disease. Additionally, during the perioperative period, patients with Cushing′s disease should undergo mandatory physical activity or prophylactic anticoagulant therapy.

We present a case of nephrogenic diabetes insipidus secondary to primary Sj?gren′s syndrome. At onset, the patient exhibited a urine output of up to 10 liter per day. Diagnostic evaluation and clinical features confirmed renal diabetes insipidus due to primary Sj?gren′s syndrome. A review of the literature indicates that primary Sj?gren′s syndrome can involve renal manifestations, including renal tubulointerstitial inflammation and impaired renal concentration ability. However, nephrogenic diabetes insipidus with such high urine output is uncommon. Management of this condition requires proactive control of the underlying disease, potassium supplementation, and urine management.

Carotenoids are secondary metabolite responsible for colored pigments in plants and microbes (Li et al., 2022). They are a class of C₄₀ tetraterpenoids consisting of eight isoprenoid units, and can be classified into carotenes and xanthophylls on the basis of their functional groups (Saini et al., 2015). Carotenes can be linear (phytoene, phytofluene, and ζ‍-carotene) or branched (β‍-carotene and α‍-carotene). Xanthophylls comprise β,β‍-xanthophylls (β‍-cryptoxanthin, zeaxanthin, violaxanthins, and neoxanthin) and β,ε‍-xanthophylls (α-cryptoxanthin, α-carotene, and lutein). Citrus fruits are complex sources of carotenoids, which are the principal pigments responsible for the typical orange color of most types (Chen, 2020). The difference in total carotenoid content and the diversity of carotenoid isomer proportion also accounts for other colors of citrus fruits, such as yellow, red, and pink (Chen, 2020).
Citrus/metabolism* ; Carotenoids ; Xanthophylls ; Lutein/metabolism* ; Zeaxanthins/metabolism* ; Fruit

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

Objective:To investigate the level and clinical significance of peripheral blood CD4 +T cell subpopulations in late-onset systemic lupus erythematosus (SLE) patients. Methods:This study included 260 SLE patients hospitalized in the Rheumatology and Immunology Department of the Second Hospital of Shanxi Medical University from January 2016 to December 2021: of whom 58 and 202 were late- (≥50 years) and adult-(18~49 years) onset patients. This study also included 160 subjeces as healthy controls(HCs), of whom 35 and 125 were Control Group 1 (≥50 years) and Control Group 2 (18~49 years). Peripheral blood CD4 +T lymphocyte subsets of these participants were assessed by flow cytometry. The clinical data of all patients and healthy controls (HCs)were recorded. The differences between the groups were analyzed by Mann-Whitney U test or χ2 test. Results:(1)The time of diagnosis of late-onset SLE was longer than that of adult-onset SLE [Median time: 5.0 (2.0, 24.0)months vs 3.0 (1.0, 7.3)months, Z=-3.13, P=0.002]. Compared with adult-onset SLE, the SLEDAI score of late-onset SLE was lower [12.0 (8.0, 15.2) vs 14.0 (10.0, 18.0), Z=-2.12, P=0.034]. Some manifestations occurred more frequently in late-onset SLE, such as weight loss, nausea, abdominal pain, cerebral infarction, interstitial pneumonitis, Sj?gren′s syndrome and infection. The manifestations of skin and mucos a occurred less frequently in late-onset SLE. (2)CD4 +T cell subpopulations: ①The absolute counts of Treg, Th17, Th1 and Th2 cells in the peripheral blood of patients with late-onset SLE were significantly lower than those of HCs [Treg: 10.94 (6.14, 19.23) vs 32.65 (28.07, 41.65), Z=-6.79, P<0.001; Th17: 3.43 (0.94, 5.64) vs 6.13 (3.77, 7.82), Z=-3.24, P=0.001; Th1: 36.02 (10.80, 76.38) vs 128.70(89.82, 159.89), Z=-5.29, P<0.001; Th2:3.56 (1.56, 6.06) vs 8.25 (4.69, 12.98), Z=-4.57, P<0.001]. The ratio of Th17/Treg cells was higher than that of HCs[0.28(0.13, 0.59) vs 0.17 (0.12, 0.28), Z=-2.38, P=0.017].②The absolute counts of Treg, Th17, Th1 and Th2 cells in peripheral blood of patients with adult-onset SLE were significantly lower than those of HCs [Treg: 10.28 (5.37, 17.04) vs.30.19 (21.20, 39.75), Z=-11.28, P<0.001; Th17: 3.44 (1.84, 6.14) vs 6.48 (4.23, 10.66), Z=-6.53, P<0.001; Th1: 29.59(15.14, 56.81) vs 90.75(42.67, 162.00), Z=-7.01, P<0.001; Th2: 2.74 (1.62, 4.77) vs 8.25 (4.75, 11.99), Z=-9.91, P<0.001]. The ratio of Th17/Treg was higher than that of HCs[0.35 (0.17, 0.65) vs 0.23(0.14, 0.37), Z=-3.89, P<0.001].③The ratios of Th17/Treg in patients with late-and adult-onset SLE were higher than those of HCs. The ratio of Th17/Treg was the highest in adult-onset SLE patients. Conclusion:Patients with late-onset SLE have reduced numbers of Treg cells and the immune imbalanced of Th17/Treg. However, the immune imbalance of Th17/Treg in late-onset SLE patients is milder than that in adult-onset SLE patients, which may be related to lower disease activity.

Objective:To investigate the level of peripheral blood regulatory T cells in rheumatoid arthritis (RA) patients with cardiovascular disease (CVD) and its clinical significance.Methods:A total of 191 patients with RA in the Department of Rheumatology and Immunology, the Second Affiliated Hospital of Shanxi Medical University and 86 healthy controls (HCs) were enrolled from January 2019 to January 2021. All peripheral blood CD4 + T lymphocyte subsets of participants were assessed by flow cytometry. Patients were divided into RA-CVD group ( n=71) and RA only group ( n=120) and their clinical data were recorded. The differences between the groups were analyzed by Independent-Samples t test, Mann-Whitney U test or χ2 test, and risk factors that affected CVD were analyzed using Logistic regression. Results:① The age of patients and the proportion of male patients in the RA-CVD group were significantly higher than those in the RA only group [age: (64±10) years old vs (56±12) years old, t=-4.16, P<0.001; male patients: 35 cases vs 31 cases, χ2=10.86, P=0.001]. ② The level of Treg cells in the peripheral blood of patients with RA only and RA-CVD groups was significantly lower than that of HCs ( Z=-4.14, P<0.001; Z=-6.27, P<0.001), while the numbers of peripheral Th17 cells in the two groups of patients were not significantly different from those of HCs ( P>0.05). The ratios of Th17/Treg cells in the two group patients were higher than those of HCs, but only the difference between RA-CVD patients and HCs was significant ( Z=-5.49, P<0.001). ③ Compared with the RA only group, the absolute number of Treg cells in peripheral blood of RA-CVD group was significantly lower [19.00(13.62, 26.73) vs 24.94 (19.32, 34.12), Z=-3.19, P=0.001], the level of Th17 cells was significantly higher [absolute number: 7.77 (3.86, 13.64) cell/μl vs 5.59 (3.49, 8.91) cells/μl, Z=-2.14, P=0.033; percentage: 1.37%(0.78, 2.00)% vs 0.80%(0.56, 1.24)%, Z=-4.20, P<0.001], and the ratio of Th17/Treg cells was significantly higher [0.40(0.24, 0.62) vs 0.23(0.14, 0.35), Z=-4.46, P<0.001]. ④ Logistic regression analysis showed that Treg cell [ OR(95% CI)=0.934 (0.903, 0.967)] was a protective factor, while elder age [ OR(95% CI)=1.038(1.003, 1.074), male [ OR(95% CI)=2.450(1.005, 5.973)], hypertension [ OR(95% CI)=2.654 (1.219, 5.779)] and Th17 cell [ OR (95% CI)=1.066 (1.019, 1.116)] were risk factors of RA complicated with CVD. Conclusion:The level of Treg cells in peripheral blood of RA patients with CVD decreases significantly, and the immune imbalance of Th17/Treg is more singificant than that of RA patients without CVD. It is suggested that the immune imbalance and dysfunction caused by the number and/or functional deficiency of Treg cells may be involved in the occurrence and development of RA complicated with CVD.