The introduction of immunotherapy has changed the traditional paradigms in cancer treatment and has demonstrated substantial clinical benefits across various malignancies. However, this progress is accompanied with emerging challenges, such as immune evasion and low response rates to immunotherapy. As an immunomodulatory molecule, zymogen granule protein 16 (ZG16) plays a crucial role in immunotherapy by inhibiting the binding of programmed death 1 (PD-1) to its ligand PD-L1, preventing immune evasion and restoring the immune system's ability to recognize and eliminate tumor cells. ZG16 is downregulated in multiple gastrointestinal tumors, and its regulatory mechanisms vary depending on the tumor type. ZG16 expression is closely associated with patient prognosis, and it has been identified as a favorable prognostic marker in colorectal cancer. This article provides a systematic overview of the structural characteristics, expression regulation mechanisms, and antitumor immune functions of ZG16.

Objective To analyze the incidence and mortality of lung cancer in 2022 globally and in China by combining gender,age,and human development index(HDI)based on the Global Cancer Statistics 2022 issued by the International Agency for Research on Cancer.Methods Lung cancer data from 185 countries and territories worldwide were obtained from the GLOBOCAN 2022 database,and the HDI was organized based on data from the Human Development Report 2021 published by the United Nations Development Program.Cancer data were stratified by age,gender,and HDI to describe the prevalence of lung cancer globally and in China.Pearson correlation analysis was used to assess the correlations between age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),mortality-to-incidence ratio(M/I)and HDI.Results In 2022,the total number of global lung cancer incidence was 2 481 000,ranking the 1st among all cancers,and the ASIR(23.6/100 000)ranked the 3rd among all cancers;the total number of global lung cancer deaths was 1 817 000,ranking the 1st among all cancers,and the ASMR(16.8/100 000)ranked the 1st among all cancers.In 2022,the total number of lung cancer incidence in China was 1 061 000,ranking the 1st among all cancers in China,accounting for 42.8%of the global lung cancer,and the ASIR(40.8/100 000)ranked the 1st among all cancers in China.The total number of lung cancer deaths was 733 000,ranking the 1st among all cancers in China,accounting for 40.4%of the global lung cancer deaths,and the ASMR(26.7/100 000)ranked the 1st among all cancers in China.The number of lung cancer incidence and deaths,ASIR,and ASMR in men were higher than those in women both globally and in China.The incidences of lung cancer,ASIR,deaths and ASMR in the world and China showed an upward trend with age,and then rapidly increased in the group older than 40-44 years group.ASIR and ASMR were positively correlated with HDI(r=0.739 3,0.686 5,both P＜0.000 1),while M/I was negatively correlated with HDI(r=-0.688 1,P＜0.000 1)in different countries and territories.Conclusion The burden of lung cancer is serious in the world and China,and the prevalence varies among countries and territories with different HDI levels,genders,and ages.

Objective:To explore the role of tumor necrosis factor receptor-associated factor 4 (TRAF4) in promoting the abnormal activation of epidermal growth factor receptor (EGFR) and its effect on lung cancer cell proliferation, migration and invasion.Methods:Tumor tissues from patients who underwent lung adenocarcinoma resection at The First Affiliated Hospital of Second Military Medical University, from January 2015 to May 2017 were collected, and the expressions of TRAF4 and Ki-67 in lung cancer tissues were detected by immunohistochemistry, the mRNA levels of Cyclin D and Vimentin were detected by real-time fluorescence quantitative PCR (qRT-PCR). The effect of TRAF4 on the tumor growth ability of lung cancer A549 cells was investigated by the xenograft model, the effect of TRAF4 or EGFR on the tumor proliferation ability was detected by using cell counting kit 8 (CCK8) and BrdU assay, and the migration and invasion abilities of tumor cells were detected by Transwell assay. Different structural domain deletion expression vectors of TRAF4 and EGFR were constructed to transfect cells, and the interaction mode of TRAF4 and EGFR was investigated by immunoprecipitation assay.Results:The expression of TRAF4 in non-small cell lung cancer (NSCLC) tissues was positively correlated with the expressions of Ki-67, cyclin D, and vimentin ( r2: 0.438, 0.695, and 0.736, respectively, all P＜0.01). Immunohistochemical assay of tumor tissues from NSCLC patients showed that tissues with high expression of TRAF4 were also high in Ki-67. Patients with high TRAF4 expression (TRAF4 positivity >30%) had a shorter progression-free survival (PFS) time than that of patients with low TRAF4 expression (TRAF4 positivity ≤30%) (median PFS of 12 and 19 months, respectively; P=0.034). Traf4 -/- cells had a weakened proliferative capacity than traf4+/+ cells and formed tumors with smaller size ( P＜0.05). The expression level of Ki-67 in the tumor tissues formed by traf4 -/- cells [(45.6±8.7)%] was lower than that in the tumor tissues formed by traf4+/+ cells [(62.3±10.3)%, P=0.015], the mRNA levels of cyclin D (1.01±0.15) and vimentin (1.01±0.12) in the traf4 -/- cells were lower than those of the traf4+/+ cells (3.41±0.32 and 3.12±0.18, respectively, both P＜0.05).The western blot results showed that, with the elevated intracellular expression level of TRAF4, phosphorylation level of EGFR was significantly increased in both wild-type EGFR and activation mutant EGFR-expression cells. The capacities of proliferation, migration and invasion of A549 cells was weakened after EGFR knockdown (all P＜0.01). Immunoprecipitation experiments showed that TRAF4 binds to the peptide segment of the near-membrane region of EGFR through the TRAF structural domain, and the mutual binding between EGFR molecules was enhanced under TRAF4 overexpression conditions. Increasing TRAF4 expression promoted EGFR molecular phosphorylation and activation of downstream signaling. Conclusions:TRAF4 expression is elevated in NSCLC tissues and tumor cells, which promotes tumor proliferation, migration and invasion. TRAF4 directly binds to EGFR molecules, enhances its own phosphorylation and activates the downstream signaling pathway by promoting the interaction between EGFR molecules.

Objective:To explore the role of tumor necrosis factor receptor-associated factor 4 (TRAF4) in promoting the abnormal activation of epidermal growth factor receptor (EGFR) and its effect on lung cancer cell proliferation, migration and invasion.Methods:Tumor tissues from patients who underwent lung adenocarcinoma resection at The First Affiliated Hospital of Second Military Medical University, from January 2015 to May 2017 were collected, and the expressions of TRAF4 and Ki-67 in lung cancer tissues were detected by immunohistochemistry, the mRNA levels of Cyclin D and Vimentin were detected by real-time fluorescence quantitative PCR (qRT-PCR). The effect of TRAF4 on the tumor growth ability of lung cancer A549 cells was investigated by the xenograft model, the effect of TRAF4 or EGFR on the tumor proliferation ability was detected by using cell counting kit 8 (CCK8) and BrdU assay, and the migration and invasion abilities of tumor cells were detected by Transwell assay. Different structural domain deletion expression vectors of TRAF4 and EGFR were constructed to transfect cells, and the interaction mode of TRAF4 and EGFR was investigated by immunoprecipitation assay.Results:The expression of TRAF4 in non-small cell lung cancer (NSCLC) tissues was positively correlated with the expressions of Ki-67, cyclin D, and vimentin ( r2: 0.438, 0.695, and 0.736, respectively, all P＜0.01). Immunohistochemical assay of tumor tissues from NSCLC patients showed that tissues with high expression of TRAF4 were also high in Ki-67. Patients with high TRAF4 expression (TRAF4 positivity >30%) had a shorter progression-free survival (PFS) time than that of patients with low TRAF4 expression (TRAF4 positivity ≤30%) (median PFS of 12 and 19 months, respectively; P=0.034). Traf4 -/- cells had a weakened proliferative capacity than traf4+/+ cells and formed tumors with smaller size ( P＜0.05). The expression level of Ki-67 in the tumor tissues formed by traf4 -/- cells [(45.6±8.7)%] was lower than that in the tumor tissues formed by traf4+/+ cells [(62.3±10.3)%, P=0.015], the mRNA levels of cyclin D (1.01±0.15) and vimentin (1.01±0.12) in the traf4 -/- cells were lower than those of the traf4+/+ cells (3.41±0.32 and 3.12±0.18, respectively, both P＜0.05).The western blot results showed that, with the elevated intracellular expression level of TRAF4, phosphorylation level of EGFR was significantly increased in both wild-type EGFR and activation mutant EGFR-expression cells. The capacities of proliferation, migration and invasion of A549 cells was weakened after EGFR knockdown (all P＜0.01). Immunoprecipitation experiments showed that TRAF4 binds to the peptide segment of the near-membrane region of EGFR through the TRAF structural domain, and the mutual binding between EGFR molecules was enhanced under TRAF4 overexpression conditions. Increasing TRAF4 expression promoted EGFR molecular phosphorylation and activation of downstream signaling. Conclusions:TRAF4 expression is elevated in NSCLC tissues and tumor cells, which promotes tumor proliferation, migration and invasion. TRAF4 directly binds to EGFR molecules, enhances its own phosphorylation and activates the downstream signaling pathway by promoting the interaction between EGFR molecules.

Objective:To survey the knowledge levels about diagnosis and management of asthma among general practitioners in community health centers in Shanghai and to analyze influencing factors.Methods:A questionnaire survey was conducted from May to June 2022 among general practitioners from 80 community health care centers in Shanghai. The questionnaire contained the basic information of the responders; knowledge about the diagnosis of asthma (symptoms, diagnostic methods, interpretation of bronchodilation and fractional exhaled nitric oxide, FeNO tests); and treatment of asthma (choosing and usage of therapeutic drugs). Logistic regression was used to analyze.Results:A total 324 general practitioners completed the questionnaire survey. Among them 221 (68.21%) had bachelor degree; 200 (61.73%) were attending doctors; the median working duration was 11 years; 174 (53.70%) had training on asthma knowledge in last 3 years. The survey results showed that 55 (16.98%) responders misinterpreted results of bronchodilation test, and 90(5.86%)misinterpreted results of FeNO test for diagnosis of asthma; 244 responders (75.31%) suspected implication of long-term cough for diagnosis of asthma; 277(85.49%)would order bronchodilation text to suspected patients; 273(84.26%)prescribed inhaled corticosteroid plus long-acting beta-2 agonist to asthma patients. For mild asthma patients, 144 responders(44.44%)suggested to use budesonide formoterol as needed; for moderate to severe asthma, 174(53.70%)suggested to use budesonide formoterol regularly and as needed, 100(30.86%)suggested to use salmeterol fluticasone regularly and salbutamol as needed. Logistic analysis showed that longer working duration was correlated with higher misinterpretation rate of bronchodilation and FeNO tests( OR=0.798,95% CI:0.694-0.918, P=0.002; OR=0.859,95% CI:0.739-0.998, P=0.047). The accuracy rate of all the questions was significantly higher in general practitioners who had training on asthma knowledge than those who didn′t receive training in last 3 years(all P<0.05). Conclusions:Most general practitioners in community health service centers in Shanghai have relatively high levels of knowledge about diagnosis and treatment of asthma. Years of work experience and training experience can affect the levels of asthma knowledge among community general practitioners.

Objective To observe the host response and the expression of interleukin-4 (IL-4) in different cross-linked hyaluronic acid composite gels at different time points after the implantation in vivo, and to explore the significance of biocompatibility and macrophage polarization in post-implantation inflammatory response and tissue remodeling. Methods New Zealand white rabbits were respectively injected with crosslinked hyaluronic acid-crosslinked hydroxypropyl methylcellulose gel (sample 1), crosslinked hyaluronic acid-hydroxypropyl methylcellulose gel (sample 2) and commercially available modified sodium hyaluronate gel (control) in subcutaneous tissue at both sides of the spine. Then the rabbits were dissected at 1, 4 and 12 weeks after the implantation. The tissues were fixed with 10％formaldehyde solution, embedded in paraffin and sliced. Hematoxylin-eosin (HE) staining was performed to observe the degree of inflammation and fibrosis. Masson staining was performed to observe the formation of collagen fibers. Immunohistochemical staining was performed to observe the expression of IL-4. Results The results of HE staining showed that the inflammatory reaction in the sample 1 and sample 2 groups was significantly higher than that in the control group 1 and 4 weeks after the implantation. The inflammatory cells aggregated, and the wall of capsule and microcapsule was thick. The sample 1 group was more obvious, and the result was mild stimulation. For all the groups, the results were all non-irritating at 12 weeks after the implantation. The results of Masson staining showed that the collagen fibers in the sample 1 and sample 2 groups were increased compared with the control group, mainly distributed around the implantation site, and a small amount among the gels after 1 and 4 weeks. After 12 weeks, the collagen fibers were further increased, especially among the gels, which were consistent with the control group. The results of immunohistochemical staining showed that, at the same time point, the expression of IL-4 in sample 1 and sample 2 groups was higher than that in the control group, and the expression of IL-4 increased gradually with time. The expression of IL-4 in the control and sample 1 group at 12 weeks after the implantation was higher than that at 1 and 4 weeks respectively, and the differences were statistically significant (all P<0.05). In the sample 1 group, the expression of IL-4 at 12 weeks after the implantation was higher than that at 1 week, and the difference was statistically significant (P<0.05). The expression of IL-4 in the sample 1 group was significantly higher than that in the control group at 4 weeks after the implantation, and the difference was statistically significant (P<0.05). Conclusions The two different cross-linked sodium hyaluronate composite gels have good biocompatibility. The formation of collagen fiber and the expression of IL-4 can gradually increased within 12 weeks after the subcutaneous implantation, which is beneficial to the tissue remodeling.

Objective To explore the effect and significance of clinical pathway guided teaching in the residency standard training program of respiratory medicine. Methods Total 47 resident physicians were selected and divided into clinical pathway group and control group from March 2014 to November 2014. The pathway group (n=24) was introduced into the teaching guided by clinical pathway management. The control group (n=23) was taught by traditional teaching method. All physicians were tested for the basic theory and the ability of case analysis after 4 weeks training. The ability of chemotherapy strategy ordered by residents independently and correctly was assessed each week during training. A satisfaction questionnaire survey was conducted to evaluate the effectiveness and satisfaction of teaching guided by clinical pathway. GraphPad Prism 5.0 was used and T test was done for comparison of data between groups. Results The medical records about basic theory and case analysis in the pathway group was higher than those in the control group with significant statistical difference (P<0.05). The records of resident physicians who could issue orders for chemotherapy independently and correctly were (70.75±2.79), (81.43±1.91), (85.23±1.3), (90.62±2.34) in the pathway group and (69.65±2.06), (77.11±2.21), (80.3±1.96), (87.78±2.21) in the control group at each week time point. There was statistical increase of the records in the pathway group than in the control group since the second week time point (P<0.05) The overall satisfaction of the pathway group was 95.84%(23/24), and the teaching satisfaction was higher than that of the control group(91.29%, 21/23). Pathway group doctors believe that the relevant teaching effectively improve the level of their knowledge , experience and ability. Conclusions The teaching method guided by clinical pathway is help-ful to standardize the teaching behavior, develop the standardized medical behavior of resident physicians, improve their clinical working ability efficiently, promote the relationship between teaching and studying, which is worth application in the residency standard training program of respiratory medicine.

Along with prolongation of overall survival and increasing of therapeutic methods in advanced non-small cell lung cancer, whole-process management has become more and more important. We reviewed the whole-process management strategy according to difference of mutation state of epidermal growth factor receptor (EGFR) gene.

OBJECTIVETo synthesize a novel nano-antibacterial inorganic filler and provide a new way to give dental composite resin antibacterial property.

METHODSQuaternary ammonium iodide N,N,N-trimethyl-3-(trimethoxysilyl) propan-1-aminium iodide were organically synthesized firstly and then the N,N,N-trimethyl-3-(trimethoxysilyl) propan-1-aminium iodide was grafted to the nano-silica particle to synthesize the antihacterial inorganic fillers nano-silica particle grafted with quaternary ammonium salt. All the products were analyzed and identified by infrared spectrum analysis. Then Streptococcus mutans were chosen as experimental object to analysis the antibacterial property of nanoantibacterial inorganic filler.

RESULTSQuaternary ammonium salt was grafted to the surface of nano-silica particles successfully by infrared spectrum analysis. Compared with the control group, the nano-silica particle grafted with quaternary ammonium salt had a strong bactericidal effect on Streptococcus mutons (P < 0.01).

CONCLUSIONThe nano-silica particle grafted with quaternary ammonium salt has a strong antibacterial property and could be used to improve dental composite resin antibacterial property.

Objective:To investigate the effects of N-acetylcysteine(NAC)on the number of Clara cells and secretion of Clara cell16000(CC16)protein in murine asthmatic model.Methods:The murine asthmatic model was established by sensitiz-ing and challenging BALB/c mice with ovalbumin(OVA).Thirty mice were divided into control,asthmatic and NAC groups (n=10). The number of Clara cells and synthesis of CC16were determined by immunohistochemistry.The CC16level in bronchoalveolar lavage fluid(BALF)was determined by Western blot.Results:The proportions of Clara cells in terminal and respiratory bronchioles were(58.05?3.75)%and(63.70?1.79)%in the asthmatic group,(74.54?5.81)%and (78.46?1.68)% in the control(P