Objective To explore the targets and mechanisms of Tongguanteng Injection in inhibiting the proliferation and migration of cervical cancer.Methods The biological activity of Tongguanteng Injection in inhibiting human cervical cancer SiHa cells was determined by MTT method.Detecting the effect of Tongguanteng Injection on SiHa cell migration through wound healing assay.Using network pharmacology to collect the key targets for treating cervical cancer,and perform molecular docking and enrichment analysis on the targets.Immunohistochemistry and Western blot were used to detect the key proteins to validate the network pharmacology predictions.Result Tongguanteng Injection significantly inhibited the proliferation and migration in a dose-dependent manner in human cervical cancer SiHa cells.Based on the main active ingredients of Marsdenia tenacissima,81 therapeutic targets for cervical cancer were obtained,which may treat cervical cancer by affecting key proteins such as FGF2,MAPK1,and MAPK3.Immunohistochemical results indicated that FGF2,MAPK1 and MAPK3 were expressed in cervical cancer tissues.The western bolt assays showed that Tongguanteng Injection could significantly reduce the FGF2 protein expression.Meanwhile,the MAPK1 and MAPK3 protein expressions were significantly increased.Conclusion Tongguanteng Injection may regulate the FGF2,MAPK1 and MAPK3,effectively impede the proliferation and migration of cervical cancer.

Objective:To systematically analyze the incidence and influencing factors of frailty in elderly patients with hematologic malignancies.Methods:Research on frailty in elderly patients with hematologic malignancies was retrieved from Chinese and English databases such as China National Knowledge Infrastructure, Wanfang Data, PubMed, and Web of Science. The search period was from database establishment to August 23, 2024. Two researchers screened the included studies, conducted quality assessment, and extracted data. Meta-analysis was conducted using Stata 18 and RevMan 5.4.Results:A total of seven studies were included, encompassing 19 076 elderly hematologic malignancy patients, with a frailty incidence of 59% [95% CI (0.48, 0.69) ]. Meta-analysis revealed that age [ MD=4.31, 95% CI (3.67, 4.96) ], gender [ OR=0.88, 95% CI (0.83, 0.93) ], alcohol consumption [ OR=1.67, 95% CI (1.15, 2.44) ], self-care ability [ MD=-1.79, 95% CI (-3.17, -0.41) ], anemia [ OR=6.67, 95% CI (2.94, 15.14) ], infection [ OR=1.81, 95% CI (1.16, 2.84) ], and neuropathy [ OR=2.52, 95% CI (1.38, 4.61) ] were the influencing factors of frailty in elderly patients with hematologic malignancies. Conclusions:The incidence of frailty is high in elderly patients with hematologic malignancies. Elderly patients with hematologic malignancies who are older, female, consume alcohol, have low self-care ability, anemia, infections, and neuropathy are prone to frailty. Healthcare providers can conduct early screening and intervention for high-risk populations of frailty based on risk factors to improve the quality of life for elderly hematologic malignancy patients.

Objective:To systematically analyze the incidence and influencing factors of frailty in elderly patients with hematologic malignancies.Methods:Research on frailty in elderly patients with hematologic malignancies was retrieved from Chinese and English databases such as China National Knowledge Infrastructure, Wanfang Data, PubMed, and Web of Science. The search period was from database establishment to August 23, 2024. Two researchers screened the included studies, conducted quality assessment, and extracted data. Meta-analysis was conducted using Stata 18 and RevMan 5.4.Results:A total of seven studies were included, encompassing 19 076 elderly hematologic malignancy patients, with a frailty incidence of 59% [95% CI (0.48, 0.69) ]. Meta-analysis revealed that age [ MD=4.31, 95% CI (3.67, 4.96) ], gender [ OR=0.88, 95% CI (0.83, 0.93) ], alcohol consumption [ OR=1.67, 95% CI (1.15, 2.44) ], self-care ability [ MD=-1.79, 95% CI (-3.17, -0.41) ], anemia [ OR=6.67, 95% CI (2.94, 15.14) ], infection [ OR=1.81, 95% CI (1.16, 2.84) ], and neuropathy [ OR=2.52, 95% CI (1.38, 4.61) ] were the influencing factors of frailty in elderly patients with hematologic malignancies. Conclusions:The incidence of frailty is high in elderly patients with hematologic malignancies. Elderly patients with hematologic malignancies who are older, female, consume alcohol, have low self-care ability, anemia, infections, and neuropathy are prone to frailty. Healthcare providers can conduct early screening and intervention for high-risk populations of frailty based on risk factors to improve the quality of life for elderly hematologic malignancy patients.

Objective To explore the targets and mechanisms of Tongguanteng Injection in inhibiting the proliferation and migration of cervical cancer.Methods The biological activity of Tongguanteng Injection in inhibiting human cervical cancer SiHa cells was determined by MTT method.Detecting the effect of Tongguanteng Injection on SiHa cell migration through wound healing assay.Using network pharmacology to collect the key targets for treating cervical cancer,and perform molecular docking and enrichment analysis on the targets.Immunohistochemistry and Western blot were used to detect the key proteins to validate the network pharmacology predictions.Result Tongguanteng Injection significantly inhibited the proliferation and migration in a dose-dependent manner in human cervical cancer SiHa cells.Based on the main active ingredients of Marsdenia tenacissima,81 therapeutic targets for cervical cancer were obtained,which may treat cervical cancer by affecting key proteins such as FGF2,MAPK1,and MAPK3.Immunohistochemical results indicated that FGF2,MAPK1 and MAPK3 were expressed in cervical cancer tissues.The western bolt assays showed that Tongguanteng Injection could significantly reduce the FGF2 protein expression.Meanwhile,the MAPK1 and MAPK3 protein expressions were significantly increased.Conclusion Tongguanteng Injection may regulate the FGF2,MAPK1 and MAPK3,effectively impede the proliferation and migration of cervical cancer.

Objective:To investigate the effect and related mechanism of Marsdenia tenacissima combined with XELOX solution on disulfide apoptosis in human colorectal cancer HCT116 cells.Methods:The human colorectal cancer HCT116 cells were cultured in vitro and treated with different concentrations of capecitabine (0, 0.3, 0.6, 1.2, 2.4, 4.8 μg/ml), oxaliplatin (0, 10, 20, 40, 80, 160 μg/ml), Marsdenia tenacissima (0, 15, 30, 60, 120, 240 mg/ml), and the glucose inhibitor BAY-876 (0, 4, 8, 16, 32, 64 μg/ml), respectively. Furthermore, the HCT116 cells were pre-treated with 25 μg/ml of BAY-876, followed by exposure to the specified concentrations of each drug group. HCT116 cells were divided into the following groups: negative control group (no treatment), capecitabine group (4.0 μg/ml), oxaliplatin group (90 μg/ml), Marsdenia tenacissima group (140 mg/ml), XELOX solution group (4.0 μg/ml capecitabine+90 μg/ml oxaliplatin), and Marsdenia tenacissima combined with XELOX solution group (140 mg/ml Marsdenia tenacissima+4.0 μg/ml capecitabine+90 μg/ml oxaliplatin). BAY-876 treatment groups refer to the groups which the glucose inhibitor BAY-876 25 μg/ml was added to each of the above groups. The cell proliferation was assessed using the MTT assay. Apoptosis was determined through Annexin Ⅴ-FITC/PI double staining. The concentration of glucose was quantified using the o-toluidine method. NADPH levels were measured by colorimetry. Cystine uptake fluorescence assay was utilized to quantify the fluorescence intensity of cystine, and cysteine content was determined using cysteine colorimetry. Results:After 0, 0.3, 0.6, 1.2, 2.4, 4.8 μg/ml concentration of capecitabine, 0, 10, 20, 40, 80, 160 μg/ml concentration of oxaliplatin, 0, 4, 8, 16, 32, 64 μg/ml concentration of BAY-876, and after pre-treatment with 25 μg/ml glucose inhibitor BAY-876, HCT116 cells were treated with the above drugs and concentrations, there were statistically significant differences in cell survival rate ( F=644.60, P<0.001; F=417.30, P<0.001; F=1 028.00, P<0.001; F=1 066.00, P<0.001; F=847.70, P<0.001), and with the increase of each drug concentration, the activity of HCT116 cells decreased gradually (all P<0.05). After 0, 15, 30, 60, 120, 240 mg/ml concentration of Marsdenia tenacissima, and after pre-treatment with 25 μg/ml glucose inhibitor BAY-876, HCT116 cells were treated with the above drugs, there were statistically significant differences in cell survival rate ( F=107.50, P<0.001; F=619.70, P<0.001), and with the increase of drug concentration, the activity of HCT116 cells increased first and then decreased (all P<0.05). Annexin Ⅴ-FITC/PI staining showed that the intensity of green, red and yellow fluorescence was weaker in the negative control group. The expression of green fluorescence and red fluorescence was enhanced in each drug group. In capecitabine group, the red fluorescence and yellow fluorescence were larger. The proportion of green fluorescence in oxaliplatin group and Marsdenia tenacissima group was smaller. The proportion of green fluorescence and yellow fluorescence in XELOX solution group was higher than that in capecitabine group and oxaliplatin group. Marsdenia tenacissima combined with XELOX solution group had the highest proportion of green and red fluorescence. After pre-treatment with the glucose inhibitor BAY-876, the green and yellow fluorescence of the cells in each group increased significantly. The green and yellow fluorescence of capecitabine group and oxaliplatin group increased significantly. The fluorescence of XELOX solution group was significantly higher than that of capecitabine group and oxaliplatin group. In Marsdenia tenacissima combined with XELOX solution group, the proportion of fluorescence expressing three colors was the largest. In the negative control group, capecitabine group, oxaliplatin group, Marsdenia tenacissima group, XELOX solution group, Marsdenia tenacissima combined with XELOX solution group, and the groups after BAY-876 pre-treatment, the glucose concentration of HCT116 was (19.91±0.13), (22.82±0.88), (11.87±0.14), (17.93±0.14), (10.53±0.10), (7.56±0.08), (11.44±0.10), (11.73±0.72), (8.98±0.40), (14.25±0.33), (6.77±1.50), and (1.56±0.17) μg/ml, respectively, with statistically significant differences ( F=762.60, P<0.001; F=118.80, P<0.001). Compared with the untreated groups, the intracellular glucose concentration of HCT116 cells treated with BAY-876 was significantly decreased ( t=86.50, P<0.001; t=16.90, P<0.001; t=11.83, P<0.001; t=17.79, P<0.001; t=4.35, P=0.012; t=54.34, P<0.001). NADPH levels in each group were (131.80±2.61), (93.87±1.00), (136.50±3.69), (105.70±0.84), (146.90±2.94), (105.00±2.25), (92.33±0.23), (88.63±0.31), (97.33±2.02), (81.77±1.33), (102.80±1.61), and (85.13±0.45) nmol/gProt, respectively, with statistically significant differences ( F=225.60, P<0.001; F=125.50, P<0.001) ; Compared with the untreated groups, the intracellular NADPH levels of HCT116 cells treated with BAY-876 was significantly decreased ( t=26.11, P<0.001; t=8.62, P<0.001; t=16.13, P<0.001; t=26.38, P<0.001; t=22.78, P<0.001; t=14.97, P<0.001). The fluorescence intensity of cystine in each group was 607.30±8.76, 655.70±6.57, 647.10±19.35, 737.80±6.34, 756.00±8.65, 846.60±11.70, 929.60±6.88, 1 049.00±22.35, 1 021.00±29.49, 1 094.00±16.17, 1 137.00±10.08, and 1 230.00±46.57, respectively, with statistically significant differences ( F=188.00, P<0.001; F=48.32, P<0.001). Compared with the untreated groups, the intracellular fluorescence intensity of cystine of HCT116 cells was significantly increased after treatment with BAY-876 ( t=50.09, P<0.001; t=29.26, P<0.001; t=18.34, P<0.001; t=35.53, P<0.001; t=49.66, P<0.001; t=13.83, P<0.001). The contents of cysteine in each group were (457.00±30.69), (581.20±30.69), (326.40±5.49), (374.20±5.54), (565.30±5.54), (246.80±30.69), (100.30±16.57), (472.90±19.10), (262.70±28.65), (348.70±9.55), (533.40±11.03), (30.23±5.49) μmol/L, respectively, with statistically significant differences ( F=110.00, P<0.001; F=423.50, P<0.001). Compared with the untreated groups, the intracellular contents of cysteine of HCT116 cells treated with BAY-876 was significantly decreased ( t=17.71, P<0.001; t=5.19, P=0.006; t=3.78, P=0.019; t=4.00, P=0.016; t=4.47, P=0.011; t=12.03, P<0.001) . Conclusion:Marsdenia tenacissima combined with XELOX solution can promote HCT116 cell death through disulfide apoptosis.

Objective:To explore the influencing factors of seasonal influenza among pregnant woman in Suzhou from 2015 to 2018.Methods:Based on the data of the influenza follow-up cohort of pregnant women in Suzhou from 2015 to 2018, the basic and clinical characteristics of the cohort were described, and the influencing factors of laboratory-confirmed influenza cases in pregnant women were analyzed by unconditional logistic regression.Results:A total of 19 006 pregnant women were recruited, in whom 479 cases of influenza were laboratory confirmed. Influenza A (H3N2) (42.8%) was the main sub-type. In pregnant women with exposure risk in influenza season, unconditional univariate logistic analysis showed that pregnant women or their husbands had registered permanent residence in Suzhou, pregnant women worked as childminder or nanny, had more than 2 permanent residents in the family except themselves, had medical insurance in Suzhou, had fertility insurance in Suzhou, were in the third trimester at the time of enrollment, had cough in the past month, were pregnant for the first time, had children, before and after pregnancy, spent more time outdoors than before, wore masks more often than before and had changed the frequency of gathering were all related to influenza virus infection in pregnant women. Among them, the first pregnancy, increasing the time of outdoor activity, increasing the frequency of wearing masks, and changing the frequency of gathering were important protective factors. Unconditional multivariate logistic regression analysis showed that the number of permanent residents at home was >2 (a OR=1.24, 95% CI: 1.01-1.52) and being in the third trimester, (a OR=1.56, 95% CI: 1.26-1.91) were the risk factors for maternal infection with influenza virus. Conclusion:Pregnant women with a large number of permanent residents and late pregnancy should pay attention to preventing seasonal influenza.

Objective:To understand the reinfection rate of 2019-nCoV in the previously infected population in Suzhou and compare the illness severity and prognosis of the reinfection cases with the first-time infection cases.Methods:A questionnaire survey was conducted in the persons with previous 2019-nCoV infection reported in Suzhou from January 22, 2020 to November 8, 2022 to collect the information about the incidence of reinfection of 2019-nCoV in this population from December 8, 2022 to January 18, 2023. The persons who were infected with 2019-nCoV for the first time were selected by marching the residence, age and gender at ratio of 1∶2 from 2019-nCoV infection community follow-up cohort of Suzhou. By χ2 test, the clinical symptoms and prognosis of the reinfection case and the first-time infection cases were compared. Results:The reinfection rate of 2019-nCoV was 13.01% (147/1 130) in Suzhou. No reinfection was found within 1-6 months after the first-time infection, the rate of reinfection was 10.59% (95/897) in those with interval of 7-12 months between the reinfection and the first-time infection and 45.61% (52/114) in those with the interval ≥24 months. The lowest reinfection rate was 9.09% (1/11) in those who had completed 4 doses of 2019-nCoV vaccination. The main symptoms of the reinfection cases were similar to those of the first-time infection cases. Except for dry cough, nausea/poor appetite and other symptoms, there were significant differences in other clinical symptoms between the two groups ( P<0.05). In the reinfection cases, fever had shorter duration with lower body temperature. The hospital visit rate in the reinfection cases was 4.08% (6/147), lower than that in the cases with the first-time infection (11.56%, 34/294). The time for negative nucleic acid (antigen) test result and recovery from illness after the reinfection were shorter than those after the first-time infection. Conclusions:Reinfection occurred in some people who had been infected with 2019-nCoV. The interval between the reinfection and the first-time infection and the completion of the 4 doses of booster vaccination were the factors influencing the reinfection rate. The hospital visit rate in the reinfection cases was lower than that in the cases with the first-time infection. The reinfection had similar symptoms and shorter illness duration compared with the first-time infection.

[摘 要] 目的：探索南蛇藤提取物齐墩果烷型五环三萜（28-hydroxy-3-oxoolean-12-en-2-oic acid）协同miR-451对人胃癌AGS细胞增殖、迁移的影响及其可能的分子机制。方法：用miR-451过表达慢病毒感染AGS细胞，并用盐酸多西环素（DOX）10或100 ng/ml诱导24 h，构建过表达miR-451的细胞AGS/miR-451+。采用10、20、40、80、160 μmol/L的齐墩果烷型五环三萜处理AGS/miR-451+细胞，MTT法、划痕实验分别检测细胞增殖和迁移能力的变化，WB法检测细胞中mTOR通路及凋亡相关蛋白表达水平的变化。结果：成功构建过表达miR-451的AGS/miR-451+细胞。与未加药对照组相比，齐墩果烷型五环三萜处理后AGS/miR-451+细胞的增殖抑制率均呈时间和浓度依赖性升高（P<0.05或P<0.01），细胞迁移率均显著降低（P<0.05或P<0.01）。齐墩果烷型五环三萜处理组细胞中，mTOR 信号通路相关蛋白的表达量均有所降低（P<0.05或P<0.01）；凋亡相关蛋白中，Bcl2的表达量下降，BAX、caspase-3、caspase-1及细胞色素c的表达量升高（P<0.05或P<0.01）。结论：齐墩果烷型五环三萜能够协同miR-451抑制人胃癌AGS细胞的增殖与迁移，其机制可能与影响凋亡和mTOR信号通路相关蛋白的表达有关。

胰岛素样生长因子（IGF）系统是人体内的一组多肽类物质，其分泌细胞广泛分布在人体各组织中，具有促生长作用。 IGF系统能够诱导肿瘤细胞出现EMT，进而增强肿瘤细胞干性、自我更新和转移潜能，向恶性肿瘤发展。研究显示，IGF系统的过 表达与胃癌（GC）的发生存在着密切关联，例如IGF-1和IGF-1R在GC组织中就有着明显表达，其表达水平随着GC从良性到恶性 的转变而逐渐増强。近年来研究也表明， 在GC细胞癌变的过程中，EMT起着关键性的作用，它使得肿瘤细胞具备了侵袭和迁移 能力，而削弱和抑制这种能力则成为了一种有针对性的治疗方法，这其中有着很大的研究空间。临床数据显示，患者化疗前后血 清中的IGF-1表达水平也能够直接反映化疗的效果，这更显示IGF可作为GC筛查的重要标志物， 为GC精准治疗的研究提供可 靠依据。上述一系列发现，使得IGF有望成为新的判断肿瘤发生及转移的诊疗指标。

Cross-talk of intracellular signaling pathways that share common components (hubs) is organized in form of a bow-tie network topology.Signaling cross-talk is functionally pleiotropic for target genes regulation, resulting in functional redundancy, synergism and antagonism, which should be precisely controlled to prevent signaling 'leaking' or 'spillover'.Thus, the biological system has evolved multiple insulating mechanisms to achieve stimulus-specific response that maintains intracellular homeostasis.The insulation mechanism of signaling cross-talk suggests: (1) the functional duality of cross-talk molecules that determine cell fate requires selectively targeting dysregulated cross-talk molecules while protecting the normal ones from off-target or unintended effects, and we propose them as the targetable cross-talk molecules;(2) cross-talk molecules are usually carried on the macromolecular complex as their functional platforms, thus the structural plasticity of conformational changes at the interaction surface of cross-talk molecules asks for intensive work on the relationship study between drug binding and biological activity, which we propose as the accessible cross-talk molecules.Therefore, signaling cross-talk and its insulation mechanism play instructive leading roles in resolving the bottlenecks of current drug R&D and improve the clinical outcome.