Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

BACKGROUND: The relationship between quality of life at three months after lung cancer surgery and different surgical approaches is remains unclear. This study aimed to compare the quality of life of patients three months after uniportal and multiportal thoracoscopic lobectomy. METHODS: Data from patients who underwent lung surgery at the Department of Thoracic Surgery, Sichuan Cancer Hospital between April 2021 and October 2021 were collected. The European Organization for Research and Treatment of Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29) were used to collect quality of life data of the patients. Potential confounding factors in the baseline data were included in a multivariate regression model for adjustment, and the quality of life of the two groups three months postoperatively was compared with traditional clinical outcomes. RESULTS: A total of 130 lung cancer patients were included, with 57 males (43.8%) and 73 females (56.2%), and an average age of (57.1±9.5) yr. In the baseline data of the two groups, there was a statistical difference in the number of chest drainage tubes placed (P<0.001). After adjustment with the regression model, at three months postoperatively, there were no significant differences in all symptoms and functional status scores between the two groups (all P>0.05). The multiportal group had longer surgery time (120.0 min vs 85.0 min, P=0.001), postoperative hospital stay (6.0 d vs 4.0 d, P=0.020), and a higher incidence of early ≥ grade 2 complications (39.0% vs 10.1%, P=0.011) compared to the uniportal group. CONCLUSIONS Patients undergoing uniportal and multiportal thoracoscopic lobectomy have similar quality of life at three months postoperatively. The uniportal group may have certain advantages in terms of traditional clinical outcome indicators such as operation time, postoperative hospital stay, and early postoperative complications.
Male ; Female ; Humans ; Lung Neoplasms/surgery* ; Quality of Life ; Thoracic Surgery, Video-Assisted/adverse effects* ; Pneumonectomy/adverse effects* ; Postoperative Complications/surgery* ; Retrospective Studies

Telephone follow-up is one of the important ways to follow up patients. High-quality follow-up can benefit both doctors and patients. However, clinical research-related follow-up is often faced with problems such as time-consuming, laborious and poor patient compliance. The authors belong to a team that has been committed to the study of patient-reported outcomes for a long time. The team has carried out long-term follow-up of symptoms, daily function and postoperative complications of more than 1 000 patients after lung cancer surgery, and accumulated certain experience. In this paper, the experience of telephone follow-up was summarized and discussed with relevant literatures from the aspects of clarifying the purpose of clinical research follow-up, understanding the needs of patients in follow-up, and using follow-up skills.

Objective:To analyze the disease burden and change trend of lung cancer attributable to chromium in Chinese population from 1990 to 2019, and to provide reference for the formulation of health policies and strategies of disease prevention and control.Methods:In October 2022, using the data and findings of the burden of disease, injury and risk factor published in the Global Burden of Disease Study 2019 (GBD 2019), the burden of lung cancer and its changes caused by occupational hexavalent chromium exposure in Chinese population from 1990 to 2019 were analyzed according to year and gender. The average age structure of the world population was used as the standard population to calculate standardized indicators, and then compared with the global population.Results:The incidence number, death number, disability adjusted life years (DALY) of lung cancer attributable to chromium in Chinese population of 2019 were 833 cases, 790 cases and 22118 person years, respectively. Compared with 1990 (257 cases, 277 cases, 8631 person years), the increase was 224.1%, 185.2%, 156.3%, higher than the global level (101.0%, 134.2%, 117.2%). The standardized morbidity, mortality and DALY rates of lung cancer attributable to chromium in Chinese population of 2019 were 0.059/100000, 0.056/100000 and 1.555/100000, which respectively increased by 169.7%, 137.4%, 113.3% in comparison with that of 1990 (0.022/100000, 0.023/100000 and 0.729/100000). The average annual percent changes were 18.8%, 15.1% and 13.5%, which were higher than the global level (5.7%, 8.4% and 7.0%). In 2019, the DALY caused by chromium-related lung cancer in the Chinese population accounted for 0.0058% (22118/382205568) of the all-cause disease burden in the Chinese population, and 51.8% (22118/42718) of the global population. In 2019, the disease burden of lung cancer attributable to chromium was higher in males than in females, the number of incidence, death and DALY were 576 cases (69.1%), 525 cases (66.5%) and 14717 person years (66.5%), respectively.Conclusion:In 2019, the proportion of disease burden caused by lung cancer attributable to chromium in the Chinese population is low, but it accounts for a high proportion of the global population burden of lung cancer attributable to chromium, and the standardized incidence, mortality and DALY rates show an increasing trend year by year from 1990 to 2019.

Objective:To analyze the disease burden and change trend of lung cancer attributable to chromium in Chinese population from 1990 to 2019, and to provide reference for the formulation of health policies and strategies of disease prevention and control.Methods:In October 2022, using the data and findings of the burden of disease, injury and risk factor published in the Global Burden of Disease Study 2019 (GBD 2019), the burden of lung cancer and its changes caused by occupational hexavalent chromium exposure in Chinese population from 1990 to 2019 were analyzed according to year and gender. The average age structure of the world population was used as the standard population to calculate standardized indicators, and then compared with the global population.Results:The incidence number, death number, disability adjusted life years (DALY) of lung cancer attributable to chromium in Chinese population of 2019 were 833 cases, 790 cases and 22118 person years, respectively. Compared with 1990 (257 cases, 277 cases, 8631 person years), the increase was 224.1%, 185.2%, 156.3%, higher than the global level (101.0%, 134.2%, 117.2%). The standardized morbidity, mortality and DALY rates of lung cancer attributable to chromium in Chinese population of 2019 were 0.059/100000, 0.056/100000 and 1.555/100000, which respectively increased by 169.7%, 137.4%, 113.3% in comparison with that of 1990 (0.022/100000, 0.023/100000 and 0.729/100000). The average annual percent changes were 18.8%, 15.1% and 13.5%, which were higher than the global level (5.7%, 8.4% and 7.0%). In 2019, the DALY caused by chromium-related lung cancer in the Chinese population accounted for 0.0058% (22118/382205568) of the all-cause disease burden in the Chinese population, and 51.8% (22118/42718) of the global population. In 2019, the disease burden of lung cancer attributable to chromium was higher in males than in females, the number of incidence, death and DALY were 576 cases (69.1%), 525 cases (66.5%) and 14717 person years (66.5%), respectively.Conclusion:In 2019, the proportion of disease burden caused by lung cancer attributable to chromium in the Chinese population is low, but it accounts for a high proportion of the global population burden of lung cancer attributable to chromium, and the standardized incidence, mortality and DALY rates show an increasing trend year by year from 1990 to 2019.

Objective:To analyze the clinical characteristics of adult Chinese patients with syncope.Methods:This is a cross-sectional survey study. Patients with preliminary diagnosis of syncope in the Emergency Department, Geriatrics and Cardiology Outpatient Department, or Syncope Unit of 37 hospitals in 19 provinces, autonomous regions and the Hong Kong Special Administrative Region from June 2018 to March 2021 were included in this study. The clinical features of these patients with syncope were analyzed.Results:A total of 4 950 consecutive patients with syncope were included in this study. The age was (56.3±16.8)years, and 2 604 cases (52.6%) were male. The most common type of syncope was neurally mediated syncope (2 345 (47.4%)), followed by cardiac syncope (1 085 (21.9%)), orthostatic hypotensive syncope (311 (6.3%)), and unexplained syncope accounted for nearly one third (1 155 (23.3%)). Predisposing syncope was more common in patients under 65 years of age(2 066(72.4%) vs. 786(27.6%),χ 2=136.5, P<0.001). Presyncope was more common in patients with neurally mediated syncope (1 972(79.0%) vs.1 908(73.9%), χ 2=17.756, P<0.001). Premonitory symptoms were more common in women(1 837(80.0%) vs. 1 863(73.0%),χ 2=33.432, P<0.001). Presyncope syndrome was more common in patients under 65 years of age (2 482(77.8%) vs. 1 218(73.4%),χ 2=17.523, P=0.001). Cyanosis was more common in ≥65 years old patients (271(18.2%) vs. 369(12.7%), χ 2=23.235, P<0.001). Urinary incontinence was more common in old patients aged ≥65 years(252(15.2%) vs. 345(10.8%), χ 2=19.313, P<0.001). Family history was more common in patients with cardiogenic syncope compared with other types of syncope (264(24.3%) vs. 754(19.5%), χ 2=11.899, P=0.001). Hypertention(1 480(30.5%)), coronary heart disease(1 057(21.4%)), atrial flutter and atrial fibrillation(359(7.2%)), second degree atrioventricular block(236(4.8%)) were common complications of syncope. The proportion of patients with coronary heart disease was significantly higher in cardiac syncope than that of other types of syncope(417(38.4%) vs. 640(16.6%), χ 2=241.376, P<0.001). Other common complications included cerebrovascular diseases (551 (11.1%)) and diabetes mellitus (632(12.8%)). Conclusions:Neurally mediated syncope is the most common syncope in adult Chinese population. Patients with predisposing conditions and premonitory conditions are younger. Presyncope is more common in women. The proportion of family history and coronary heart disease is higher in patients with cardiogenic syncope.

Objective:To explore predictors of overall survival (OS) in Chinese patients with polycythemia vera (PV) .Methods:A total of 906 consecutive newly diagnosed patients with PV seen at the Blood Diseases Hospital, Chinese Academy of Medical Sciences, from June 2007 to February 2020 were included, and their data were collected. PV was diagnosed according to 2016 World Health Organization (WHO) diagnostic definitions. OS and prognostic factors were retrospectively analyzed.Results:Among the 906 patients, 439 were male (48.5%) and 467 were female (51.5%) . The median age was 57 years (range: 18-91 years) . 31.6% (276/874) of the patients had a thrombosis history at diagnosis, and 4.6% (25/541) of the patients had abnormal cytogenetics. The median follow-up was 54 months (95% confidence interval [ CI] 8-130 months) . The 5- and 10-year cumulative deaths were 5.8% (95% CI 4.8%-6.7%) and 11.1% (95% CI 9.3%-12.9%) , respectively. Univariate analysis showed that age ≥60 years, thrombosis history, white blood cells (WBC) ≥15×10 9/L, platelet (PLT) ≥450×10 9/L, and platelet distribution width (PDW) ≥15 fl significantly correlated with worse OS, and palpable spleen correlated with better OS. Multivariate analysis showed that age ≥60 years ( HR=4.3, 95% CI 2.1-9.2, P<0.001) and PDW ≥15 fl ( HR=2.1, 95% CI 1.1-4.0, P=0.023) were independent prognostic factors for worse OS. The 5-year cumulative death for patients with PDW ≥15 fl or PDW<15 fl was 8.6% (95% CI 5.9%-11.3%) or 4.4% (95% CI 3.4%-5.4%) , respectively. The 5-year cumulative death for patients defined as low-, intermediate-, and high-risk patients by international working group score system for PV (IWG-PV) were 0.8% (95 CI 0.2%-1.4%) , 4.0% (95% CI 2.7%-5.3%) , and 12% (95% CI 9.6%-14.4%) , respectively, with a significant difference among the three cohorts ( P<0.05) . PDW ≥ 15 fl significantly affected OS for intermediate- and high-risk patients ( HR=2.3, 95% CI 1.2-4.2, P=0.009) defined by IWG-PV score system, but not for low-risk patients ( HR=3.1, 95% CI 0.2-52.0, P=0.405) . Conclusions:Age ≥60 years and PDW ≥15 fl were independent prognostic factors for worse OS in PV. IWG-PV score system effectively predicted OS for Chinese patients with PV.

Objective:To investigate the pathological characteristics of megakaryocytes in myeloproliferative neoplasms(MPN)and their correlations with driver gene mutations.Methods:Trephine specimens administered for 160 patients with MPN from February 2012 to October 2017 were reevaluated according to the World Health Organization(WHO)’s(2016)diagnostic criteria.Results:This cohort of patients included 72(45.0%)men, with the median age of 59(range, 13-87)years, comprising 39 with polycythemia vera(PV), 33 with essential thrombocythemia(ET), 37 with prefibrotic/early-primary myelofibrosis(pre-PMF), 37 with overt PMF, 1 with post-ET MF, 2 with post-PV MF, and 11 with MPN-unclassifiable(MPN-U)after the re-diagnosis. With PV, ET, pre-PMF, and overt PMF changes, proportions of dense clusters, hypolobulated nuclei, and naked nuclei of megakaryocytes gradually increased, whereas erythropoiesis gradually decreased. Proportions of reticulin, collagen, and osteosclerosis grades of ≥1 also increased. Dense clusters, hypolobulated nuclei, and naked nuclei of megakaryocytes were negatively correlated with erythropoiesis and positively correlated with granulopoiesis and fibrosis. In patients with pre- and overt PMF, dense clusters and naked nuclei of megakaryocytes were positively correlated with fibrosis. Patients with JAK2V617F MPN had significantly increased erythropoiesis( P=0.022). Patients with CALR-mutated MPN were characterized by increased loose and dense clusters; paratrabecular distribution and naked nuclei of megakaryocytes( P=0.055, P=0.002, P=0.018, P=0.008); and increased reticulin, collagen, and osteosclerosis( P=0.003, P<0.001, P=0.001). In patients with pre- and overt PMF, patients with JAK2V617F had increased cellularity( P=0.037). CALR-mutated patients had increased dense clusters and giant sizes of megakaryocytes, collagen, and osteosclerosis( P=0.055, P=0.059, P=0.011, P=0.046). Conclusion:Megakaryocytes showed abnormal MPN morphology and distribution, which were related to fibrosis. CALR mutation was probably associated with abnormal morphology and distribution of megakaryocytes and fibrosis.

Objective:To compare fibrosis-driving cells in patients with primary myelofibrosis (PMF) and patients with myelodysplastic syndromes (MDS) with myelofibrosis (MF) (MDS-MF) .Methods:Bone marrow biopsy sections of patients with newly diagnosed PMF and MDS (10 each randomly selected for MF-0/1, MF-2, and MF-3) were stained with specific immunofluorescence antibodies to label Gli1, LeptinR, alpha smooth muscle actin (α-SMA) , CD45, and ProcollagenⅠ. Images captured by confocal microscopy were analyzed by Fiji-ImageJ to calculate the cell counts of Gli1 +, LeptinR + cells, and fibrosis-driving cells including α-SMA +, α-SMA +/Gli1 +, α-SMA +/LeptinR +, and ProcollagenⅠ +/CD45 + cells. Results:Patients with PMF and MDS with MF-2/3 had higher LeptinR +, α-SMA +, α-SMA +/Gli1 +, and Procollagen Ⅰ +/CD45 + cell counts compared with those with MF-0/1 (all P values<0.05) . However, patients with PMF with MF-2/3 presented with higher Gli1 + and α-SMA +/LeptinR + cell counts than those with MF-0/1 ( P=0.001 and 0.006) , whereas these cells were similar between patients with MDS with MF-0/1 and MF-2/3 ( P=0.169 and 0.067) . In patients with MF-0/1, all fibrosis-driving cells did not differ between PMF and MDS (all P>0.05) . However, in patients with MF-2/3, Procollagen Ⅰ +/CD45 + cell counts were higher in patients with PMF compared with those with MDS ( P=0.007) , while other fibrosis-driving cell counts were similar between these two groups (all P>0.05) . MF grade and fibrosis-driving cell counts were not correlated with overall survival in patients with either PMF or MDS. Conclusion:α-SMA + cells in patients with PMF originated from both Gli1 + and LeptinR + cells, whereas α-SMA + cells in patients with MDS-MF only originated from Gli1 + cells; patients with PMF had higher ProcollagenⅠ +/CD45 + cell counts than those with MDS-MF.

Objective:To explore the genetic characteristics, clinical features, and prognostic values of RAS mutations in patients with myelofibrosis (MF) .Methods:We analyzed 112-gene targeted sequencing data from 226 patients who had a diagnosis of either primary myelofibrosis (PMF) or post-polycythemia vera/post-essential thrombocythemia (post-PV MF and post-ET MF) from December 2011 to December 2019. A retrospective analysis of the genetic characteristics, clinical features, and prognosis of RAS mutations was performed.Results:Among 266 patients diagnosed PMF or post-PV/ET MF, RAS mutations were found in 14 (6.2%) cases, including 9 (4.0%) cases of NRAS mutations, 8 (3.5%) cases of KRAS mutations, and 3 (1.3%) cases of both NRAS and KRAS mutations. All of the NRAS mutations were located in codons 12 and 13. The median VAFs of RAS mutations were significantly lower than those of the driver mutations, confirming that they represent sub-clonal events that are acquired during the disease course. SETBP1, SRSF2, and MPL tended to be clustered with RAS mutations. Patients with RAS mutations had a higher number of additional oncogenic mutations (median, 3.36 vs 1.17, P<0.001) . RAS mutations had a statistically significant association with elevated monocyte cell counts ( P=0.003) , lower platelet counts ( P=0.026) , higher bone marrow blasts ( P=0.022) , splenomegaly ( P=0.005) , and very high-risk (VHR) karyotype abnormality percentage ( P=0.031) . In univariate analysis, the OS of patients with NRAS mutations were significantly inferior in the entire MF and PMF cohorts ( P=0.001, P=0.008) . In a multivariate model, NRAS retained an independent negative prognostic factor in PMF. Conclusion:RAS gene mutations were constantly related to elevated monocyte cell counts, lower platelet counts, higher bone marrow blasts, and VHR karyotype abnormality percentage that usually defined high-risk disease and often occurred as sub-clonal events. NRAS mutation is an independent poor prognostic factor in PMF.