Human epidermal growth factor receptor 2 (HER2) is a key therapeutic target for breast cancer. With the wide application of anti-HER2 and HER2 antibody-drug conjugates such as trastuzumab, pertuzumab, trastuzumab emtansine, and trastuzumab deruxtecan, the survival of patients with advanced HER2-positive breast cancers have been significantly improved. However, the subsequent drug-induced interstitial lung disease (DILD) has gradually become an important complication affecting the therapeutic effect and safety. However, the clinical understanding of interstitial lung disease (ILD) caused by this type of drugs is still insufficient, the management lacks unified standards, and the molecular mechanism has not been fully clarified. This study, through two clinical cases of severe DILD, explores the pathogenesis, treatment strategies, risk factors and follow-up monitoring requirements of ILD caused by HER2-targeted drugs, providing a scientific basis for optimizing the clinical diagnosis and treatment plan.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

BACKGROUND: Lung cancer is a disease with a high incidence rate in Yunnan province, yet there is a paucity of large-scale studies on its clinical epidemiology. This research aims to investigate the epidemiological characteristics of patients who underwent lung cancer surgery at Yunnan Cancer Hospital over the past decade, thereby providing a theoretical basis for the prevention and treatment of lung cancer. METHODS: Clinical data were collected from 15,967 patients who underwent lung cancer surgery at Yunnan Cancer Hospital between 2013 and 2022. A statistical analysis was conducted on the patients' general data, surgical information, pathological types of lung cancer, and other clinical epidemiological characteristics. RESULTS: Among the 15,967 cases of lung cancer, 46.3% were male and 53.7% were female, with the male-to-female ratio ranging from 0.68 to 1.61:1. The median age was 56 years (interquartile range: 49-63), and 37.0% of the patients were in the age group of 50-59 years. Since 2017, there has been an annual increase in the proportion of patients under the age of 60 years. The smoking status of the patients showed that 28.1% were smokers and 71.9% were non-smokers. Qujing city accounted for 41.4% and Kunming city for 23.2% of the cases in Yunnan province, with 29.6% of patients originating from Xuanwei and Fuyuan areas of Qujing city. The distribution of affected lung lobes was as follows: right upper lobe 28.2%, right middle lobe 6.3%, right lower lobe 20.1%, left upper lobe 22.7%, and left lower lobe 16.4%. The use of thoracoscopic surgery increased from 30.8% to 96.3%, with single-port thoracoscopic surgery comprising 61.3%. Lobectomy was performed in 64.2% of cases, wedge resection in 17.2%, and segmentectomy in 12.2%. The proportion of lobectomy decreased from 83.1% to 46.1%. The proportion of patients in stages 0-I increased from 43.5% to 82.8%, while stages II-IV decreased from 56.5% to 17.2%. Adenocarcinoma increased from 75.6% to 88.3%, and squamous cell carcinoma decreased from 21.5% to 8.6%. Among adenocarcinoma patients, 60.9% were female. Among sguamous cell carcinoma patients, 90.6% were male. The peak age for adenocarcinoma was 50-59 years, and for squamous cell carcinoma, it was 60-69 years. The smoking rate was higher among squamous cell carcinoma patients (65.9%) compared to adenocarcinoma patients (22.3%). Adenocarcinoma patients had a higher proportion in stages 0-I (76.3%), while squamous cell carcinoma patients were more prevalent in stages II-III (64.1%). CONCLUSIONS The findings indicate an increasing proportion of female patients with adenocarcinoma, a younger age of onset, a higher proportion of non-smoking lung cancer patients, and an increased proportion of stages 0-I lung cancer. These trends may reflect the epidemiological characteristics of patients undergoing lung cancer surgery in Yunnan and surrounding areas over the past decade.
Humans ; Female ; Male ; Lung Neoplasms/pathology* ; Middle Aged ; China/epidemiology* ; Aged ; Adult ; Aged, 80 and over

Objective To evaluate the relationship between quartz's deposit and expression of NF-κB in non-small cell lung cancer (NSCLC) lung tissues in Xuanwei, Yunnan Province, and to clarify the role of quartz in Xuanwei NSCLC's carcinogenic mechanism. Methods As research objects, the lung tissues of NSCLC and lung benign lesions after surgical resection were collected from July 2009 to September 2015 at the Third Affiliated Hospital of Kunming Medical University. Firstly, the transmission electron microscopic (TEM) with energy dispersive X-ray analyzer (EDS) was used for observation of crystalline deposit and local pathological changes. Secondly, expression level of NF-κB had been analysed and a correlation analysis with particle size of SiO2 crystal in the same lung sample was made. Results The occurrence rates of quartz in Xuanwei NSCLC lung tissues were above non-Xuanwei NSCLC and benign lung tissues (P<0.01);the average particle size of SiO2 crystal was (226 ± 120) nm × (237 ± 163) nm in Xuanwei NSCLC group and it was smaller than the other two groups; In Xuanwei NSCLC group, the expression level of NF-κB was significantly higher than non-Xuanwei and benign lung tissues (P< 0.01), but there was no significant difference between cancer tissues and normal lung tissues in the group (P>0.05). The expression level of NF-κB was generally increasing when quartz 's size became smaller. Conclusion Quartz 's deposit may play a certain role in carcinogenic mechanism of lung cancer in Xuanwei, the smaller the particle size, the greater the cytotoxicity.

Xuanwei district in Yunnan Province of China has pretty high incidence of lung cancer in China, even a- round the world. Studies have shown that there exists a close relationship between lung cancer and local indoor air pollution caused by Bituminous coal. Considering that the indoor air pollution in Xuanwei District is caused by "open fireplace", an indoor air pollution simulation system was designed, and an F344 rats lung damage model was estab- lished for this indoor air pollution fireplace. The model is based on indoor air pollution simulation system with signal multiplexer control and multi-channel acquisition, and mining PID algorithm was used for polynomial fitting to each test point, and a relatively constant PM2. 5 air pollution status was simulated. The results showed that the system could simulate a variety of states of air pollution, provide a new test method for evaluation of human injury caused by indoor air pollution and a new idea for the study of the incidence of lung cancer in Xuanwei district and other places.
Air Pollution, Indoor ; analysis ; Animals ; China ; Coal ; adverse effects ; Humans ; Incidence ; Lung ; drug effects ; pathology ; Lung Neoplasms ; epidemiology ; Models, Biological ; Particulate Matter ; analysis ; Rats ; Rats, Inbred F344

Objective To compare the difference in pharmacokinetics characteristics of vancomycin in cerebrospinal fluid between administration by continuous infusion and interim infusion.Methods Twenty postoperative patients in the Department of Neurosurgery of Beijing Tiantan Hospital, Capital Medical University admitted into intensive care unit (ICU) to receive vancomycin for prophylaxis of intracranial infection were enrolled, and they were randomly distributed to a continuous intravenous infusion group and a interim intravenous infusion group, each group 10 cases. In continuous intravenous infusion group, the patients received a loading dose of vancomycin (15 mg/kg) by continuous intravenous pump infusion for 1 - 2 hours followed by 30 mg/kg vancomycin in a constant pump infusion rate for 24 hours; while in interim intravenous infusion group, the patients received 15 mg/kg vancomycin administered by intravenous pump infusion for 1 - 2 hours, once every 12 hours. The concentration of vancomycin in the cerebrospinal fluid at different time points was measured by two-dimensional liquid chromatography (2D-LC) method, the parameters of pharmacokinetics were calculated in the two groups, and the adverse reaction was observed.Results The comparison between the ratio of areas under the concentration-time curves (AUC) and minimum inhibitory concentration (MIC) of the continuous and interim groups showed no significant difference (19.7±14.0 vs. 16.1±6.4,P > 0.05). However, in the continuous intravenous infusion group, the drug concentration reached the peak value (0.96± 0.77)μg/mL at 12 hours, and later revealed a plateau concentration 0.91-0.93μg/mL for 12 hours; while in the intravenous infusion interim group, the drug concentration reached the peak value (0.92±0.47)μg/mL at 16 hours, in the later 2 hours declined to (0.84±0.45)μg/mL, and afterwards still had a tendency of persistent declination. In all the patients, no any adverse reaction related to the drug occurred.Conclusion Continuous intravenous infusion and interim intravenous infusion of vancomycin for the postoperative neurosurgical patients without intracranial infection have the similar efficacy of medication, but the former can achieve the peak concentration faster and later the fluctuation of drug concentration in cerebrospinal fluid is smaller than those in the latter.

Aim To examine the inhibitory effect of re-combinant cardiac troponin fusion protein composed of subunit I and artificial peptide which was called CIS on tumor growth. Methods The CIS ’ s effect on the growth of human umbilical vein endothelial cells ( HU-VEC) was examined using MTT assay in vitro. Chick chorioallantoic membrane model was applied to study the alteration of angiogenesis treated with purified re-combinant CIS protein. The effect of tumor growth trea-ted with CIS was observed using several in vivo mice xenograft models. Results There was a statistically significant reduction in HUVEC cell proliferative rate when the cells were treated with purified CIS fusion protein, which was also shown in a dose-dependent manner. A decreased amount of new blood vessel for-mation ( angiogenesis) on chick embryo chorioallantoic membranes was observed in recombinant CIS protein treated group compared to the untreated control group. A significant inhibition of tumor growth rate was a-chieved in CIS treated mice compared to CIS untreated control mice in 6 different mouse xenograft models. Conclusions The fusion protein CIS shows the inhibi-tory effect on the tumor growth in our in vivo mouse models, and such inhibition could be mediated by the mechanism of CIS’ s effect on the decrease of HUVEC cell proliferation and further the reduction of angiogen-esis in tumor tissues. This work could provide the foundation for the in-depth investigations on the phar-maceutical application of CIS targeting anti-tumor ther-apy.

Background and objectivehTe high incidence of lung cancer in Xuanwei, China, has become an im-portant restricting factor for livelihood development, thus exerting local social and economic impacts. Coal is the main fuel of the local community and also the main source of indoor pollution. hTis study aims to explore the coal combustion inhalable ifne particulate matter (PM2.5) and its component output differences in different areas of Xuanwei, Yunnan. Moreover, the aim of this study is to investigate the relationship between inhalation of ifne particles and high incidence of local lung cancer.Meth-odsFor combustion test, coal mines designated as C1, K7 and M30 were collected from LaoLin Colliery of Laibing Town, Huchang Colliery of Baoshan Town, and Taiping Colliery of Wenxing Town in Xuanwei, respectively. PM2.5 of indoor air was weighed, analyzed for elemental composition, and morphologically compared. hTe pathological specimen of lung cancer pa-tients in Xuanwei who underwent operation was observed through electron microscope.Results hTe PM2.5 concentrations in indoor air were (8.244 ±1.460) mg/m3 (C1), (5.066±0.984) mg/m3 (K7), and (5.071±1.460) mg/m3 (M30). hTe differences among pairwise comparisons were statistically signiifcant (P=0.029). hTe iflter impurities of C1 coal seam primarily includeSi- and O-enriched compounds. Moreover, three membranes that comprised other elements, including C, S, and Si, were ob-served. hTese membranes were evident from the aggregation of silica and a Ca-Al membrane. Compared with that of other coal seams, C1 coal generated a mass of impurities, in which several particles have irregular shape. We found nanoscale ifne particles in some specimens of Xuanwei lung cancer patients.ConclusionhTe produced combustion of C1 coal was different from that of K7 and M30 coal. PM2.5 composition may be associated with the high local incidence of lung cancer.

Background and objective Lung cancer is the type of cancer with the highest incidence and mortality in numerous countries and regions. Establishing an appropriate animal model that can be used to simulate lung cancer etiology, pathogenesis, and similar processes, is urgent. We explore the feasibility of establishing a lung cancer model induced by Xuan-wei bituminous coal dust PM10 (particulate matter with diameters of 10 μm or less), which affects bronchial epithelium of tree shrews.Methods hTe neck skin of adult tree shrews is dissected, and the thyroid cartilage is fully exposed. Subsequently, the weak part at the top of the thyroid cartilage is treated with intratracheal agents by perfusion via a special infusion needle punc-ture method. Regular X-ray examination and lung tissue biopsy were performed on the sacriifced animals to observe changes in pulmonary imaging and bronchial epithelial cells atfer perfusion of Xuanwei bituminous coal dust PM 10.ResultshTe tree shrews of the experimental group (exposed to bituminous coal dust) died in a week atfer perfusion with PM10, whereas no animal died until the end of the experiment in the blank control and the solvent control groups. Sections of lung tissue biopsy of the regularly killed tree shrews were stained with hematoxylin and eosin. hTe lung tissues of tree shrews in the experimental group showed a serial changes caused by bronchial epithelial hyperplasia, such as squamous metaplasia, dysplasia, and early invasive carcinoma, whereas no signiifcant pathological changes were observed in the blank control and solvent control groups. Conclusion Endotracheal infusion of Xuanwei bituminous coal dust PM10 induces lung cancer in tree shrews. hTus, the lung cancer model was established.

Objective To detect the expression of Survivin and hypoxia inducible factor-1α (HIF-1α) in prostatic hyperplasia and prostatic carcinoma,and investigate their roles and mutual correlations in pathogenesis and progression of prostatic carcinoma.Methods The expression of Survivin and HIF-1α in proliferative lesions of prostate (15 cases) and prostatic carcinoma (62 cases) were detected by immunohistochemistry method.The relationship between the expressions of Survivin and HIF-1α was analyzed,as well as their correlations with clinicopathological features.Results The positive expression of Survivin and HIF-1α were significantly higher in the prostatic carcinoma [71.0 ％ (44/62) and 69.4 ％ (43/62),respectively] compared with those of the prostatic proliferation [6.7 ％ (1/15) and 0] (x2 =20.56,P 0.001; x2 =23.56,P =0.001,respectively).The expression of Survivin and HIF-1α in prostate carcinoma was significantly related with the histological grading,clinical staging (x2 =10.64,5.39,7.62,6.43,all P ＜ 0.05).And there was positively correlated between Survivin and HIF-lα (rs =0.350,P =0.006).Conclusion Survivin and HIF-1α synergistically play important roles in pathogenesis and progression of prostatic carcinoma.