Objectives:To examine the proportion and trends of cervical adenocarcinoma in cervical cancer (ICC), mainly including cervical adenocarcinoma (CADC) and squamous cervical cancer (SCC) in China, and to analyze the distribution of human papilloma virus (HPV) in CADC and SCC.Methods:Published studies reporting HPVs distribution in various histological types or relative proportions of CADC in ICC in China were identified manually and searched systematically in Medline, Embase, Cochrane Library databases, CNKI and Wanfang since the databases were established until October 2022. Meta-analysis was performed using Stata 16.0 software. And we applied the random-effects models to estimate the combined effect values due to the high heterogeneity.Results:Twenty-three studies were eligible. The relative prevalence of CADC was 9.0% (95% CI, 7.7%－10.3%). According to the diagnosis time of ICC, the patients were divided into three time periods, which is 1979-2005, 2006-2011, 2012-2022 respectively. The prevalence of CADC by time was: 6.0% in 1979-2005, 8.1% in 2006-2011, and 9.5% in 2012-2022, respectively, with no statistically significant trend in proportions over time (χ 2=5.03, P=0.081). Meanwhile, the percentage of CADC also varies by regions, and the highest percentage of CADC was found in the eastern region (11.2%), followed by the western region (7.3%) and the central region (5.9%). The total prevalence of HPV infection in CADC was 72.3%, which was lower than 92.0% in SCC, and the difference was statistically significant (χ 2=300.89, P＜0.01). To be specific, the top three HPV types prevalent in CADC were HPV18 (45.0%), HPV16 (22.0%), and HPV52 (7.3%), and those prevalent in the SCC were HPV16 (64.2%), HPV52 (5.6%), HPV18 (5.4%). The results of the Egger's test, and Begg's test showed that there was no publication bias in this study and sensitivity analysis showed that the results of this study were fairly stable. Conclusions:The proportion of CADC in China has increased in a limited way in the past decades, and there are regional differences in the proportion of CADC. The predominant type is HPV18 in CADC and HPV16 in SCC. To eliminate the limitations of the secondary literature, a multicenter study with consistent diagnostic levels and identical HPV genotyping tests is still needed in the future to better characterize the relative proportion of cervical adenocarcinoma and the trend of HPV changes, which will provide a basis for the improvement of HPV vaccine and screening policies.

Objectives:To examine the proportion and trends of cervical adenocarcinoma in cervical cancer (ICC), mainly including cervical adenocarcinoma (CADC) and squamous cervical cancer (SCC) in China, and to analyze the distribution of human papilloma virus (HPV) in CADC and SCC.Methods:Published studies reporting HPVs distribution in various histological types or relative proportions of CADC in ICC in China were identified manually and searched systematically in Medline, Embase, Cochrane Library databases, CNKI and Wanfang since the databases were established until October 2022. Meta-analysis was performed using Stata 16.0 software. And we applied the random-effects models to estimate the combined effect values due to the high heterogeneity.Results:Twenty-three studies were eligible. The relative prevalence of CADC was 9.0% (95% CI, 7.7%－10.3%). According to the diagnosis time of ICC, the patients were divided into three time periods, which is 1979-2005, 2006-2011, 2012-2022 respectively. The prevalence of CADC by time was: 6.0% in 1979-2005, 8.1% in 2006-2011, and 9.5% in 2012-2022, respectively, with no statistically significant trend in proportions over time (χ 2=5.03, P=0.081). Meanwhile, the percentage of CADC also varies by regions, and the highest percentage of CADC was found in the eastern region (11.2%), followed by the western region (7.3%) and the central region (5.9%). The total prevalence of HPV infection in CADC was 72.3%, which was lower than 92.0% in SCC, and the difference was statistically significant (χ 2=300.89, P＜0.01). To be specific, the top three HPV types prevalent in CADC were HPV18 (45.0%), HPV16 (22.0%), and HPV52 (7.3%), and those prevalent in the SCC were HPV16 (64.2%), HPV52 (5.6%), HPV18 (5.4%). The results of the Egger's test, and Begg's test showed that there was no publication bias in this study and sensitivity analysis showed that the results of this study were fairly stable. Conclusions:The proportion of CADC in China has increased in a limited way in the past decades, and there are regional differences in the proportion of CADC. The predominant type is HPV18 in CADC and HPV16 in SCC. To eliminate the limitations of the secondary literature, a multicenter study with consistent diagnostic levels and identical HPV genotyping tests is still needed in the future to better characterize the relative proportion of cervical adenocarcinoma and the trend of HPV changes, which will provide a basis for the improvement of HPV vaccine and screening policies.

ObjectiveTo investigate the therapeutic effect of ganoderic acid A （GA-A） on a mouse model of concanavalin A （ConA）-induced autoimmune hepatitis （AIH）. MethodsA total of 35 mice were randomly divided into control group （NC group）， model group （ConA group）， and low-， middle-， and high-dose GA-A treatment groups （GA-A-L， GA-A-M， and GA-A-H groups， respectively）， with 7 mice in each group. ConA was injected via the caudal vein of mice to establish a classic mouse model of AIH， and different doses of GA-A were administered via intraperitoneal injection 1 hour later for treatment. Proteomic techniques were used to investigate the protective mechanism of GA-A on hepatocytes， and HL-60 cells were differentiated into dHL-60 neutrophils by all-trans retinoic acid in vitro to validate the mechanism of action of GA-A. Related indicators were measured， including inflammatory markers （the activities of serum alanine aminotransferase ［ALT］ and aspartate aminotransferase ［AST］， HE staining， and inflammation-related genes）， apoptosis markers （TUNEL staining）， neutrophils， and neutrophil extracellular trap （NET） markers （myeloperoxidase ［MPO］， citrullinated histone H3 ［CitH3］， Ly6G， and free double-stranded DNA ［dsDNA］）， and p38 phosphorylation markers. The independent samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the NC group， the ConA group had significant increases in the serum levels of ALT and AST （both P<0.001）， and compared with the ConA group， GA-A treatment significantly reduced the levels of ALT and AST （both P<0.01）. HE staining showed that the mice in the ConA group had significant liver necrosis， while GA-A treatment significantly reduced the area of liver necrosis and the number of TUNEL-positive cells （both P<0.05）. Compared with the ConA group， the GA-A group had significant reductions in the expression levels of the inflammatory factors interleukin-6， tumor necrosis factor-α， and interferon gamma in serum and liver tissue （all P<0.05）. The proteomic analysis showed that GA-A alleviated ConA-induced acute immune liver injury by inhibiting the release of NET and the p38 MAPK pathway. Immunofluorescent staining of mouse liver tissue showed that compared with the ConA group， the GA-A group had significant reductions in the number of MPO-positive neutrophils and the number of cells with positive Ly6G and CitH3 （all P<0.01）. Western Blot and dsDNA testing showed that GA-A significantly inhibited the levels of the NET markers dsDNA and CitH3 and the level of p38 phosphorylation in liver tissue and dHL-60 cells （all P<0.05）. ConclusionGA-A alleviates liver inflammatory response and hepatocyte death by inhibiting the p38 MAPK pathway and the release of NET， thereby alleviating ConA-induced acute immune liver injury. This study provides a theoretical basis for the use of GA-A to treat immune liver injury by regulating neutrophil function.

Specific tumor-targeted gene delivery remains an unsolved therapeutic issue due to aberrant vascularization in tumor microenvironment (TME). Some bacteria exhibit spontaneous chemotaxis toward the anaerobic and immune-suppressive TME, which makes them ideal natural vehicles for cancer gene therapy. Here, we conjugated ZIF-8 metal-organic frameworks encapsulating eukaryotic murine interleukin 2 (Il2) expression plasmid onto the surface of VNP20009, an attenuated Salmonella typhimurium strain with well-documented anti-cancer activity, and constructed a TME-targeted Il2 delivery system named Il2/ZIF-8@Salmonella. Both in vitro and in vivo experiments demonstrated that Il2/ZIF-8@Salmonella maintained the tumor-targeting feature of bacteria, and could be effectively phagocytosed by intratumoral macrophages, thus leading to the expression and secretion of IL2 in TME. The detailed analysis of tumor immune microenvironment (TIME) showed that one dose of combinatorial Il2/ZIF-8@Salmonella achieved synergistic actions on a potent remodeling of TIME, marked by the activation of cytotoxic T cells and M1-polarization of macrophages in TME, thus leading to significant anti-tumor effects in melanoma, orthotopic hepatocellular carcinoma, and pulmonary metastasis models. More importantly, Il2/ZIF-8@Salmonella exhibited high safety to major organs and hematopoietic systems. Taken together, we report a novel plasmid/ZIF-8@Salmonella system that simultaneously achieves effective TME-targeted delivery of therapeutic gene, as well as synergistic re-activation of TIME.

Objective: To evaluate the clinical effects of CGF membrane for repairing the oral mucosa defects. Methods: 39 patients were selected with oral mucosa defects after surgical resections. 19 defects were covered by autologous CGF membranes as the experimental group. 20 defects were not covered by membrane as the control group. Regular follow-up were performed at one week, two weeks, three weeks, one month, two months, three months after the operations. And wound healings were compared in the groups. Results: CGF membranes of the 19 patients in the experimental group survived completely. And no infection occurred. The wound healing rate of the experimental group was higher than that of the control group at two weeks, three weeks and one month after the operations. And the difference was statistically significant(P<0.05). The VAS score of the experimental group was lower than that of the control group at one week, two weeks, three weeks and one month(P<0.05). The mean score of VSS score in the experimental group was lower than that in the control group (P<0.05). Conclusions Repair of the oral mucosa defects with CGF membrane can shorten the period of wound healing, relieve the postoperative discomfort and reduce the scar. It was a safe and effective method worthy to be popularized.

Objective To study the important virulence regulation genes of Brucella,and to understand their function.Methods Quantitative RT-PCR was used to quantify their relative transcription profiles under stress conditions and during macrophage cell infection.Results These genes were activated at different levels under these conditions and during cell infection,indicating their roles in pathogenesis at different srage of infection.Conclusion The transcription profiles of these genes have different effects about their functions.