Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
Humans ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Treatment Outcome

Objective: To study the effects of dihydromyricetin (DMY) on the proliferation, apoptosis and epithelial mesenchymal transition (EMT) of esophageal squamous cell carcinoma (ESCC) cell KYSE150 and KYSE410. Methods: KYSE150 and KYSE410 cells were treated with different concentrations of DMY (0, 25, 50, 100, 150, 200 μmol/L) for 24 hours. The median inhibition concentration (IC₅₀) values of KYSE150 and KYSE410 were detected by cell counting kit-8 (CCK-8) method. Then 0.5‰ dimethyl sulfoxide (DMSO) was used as control group, dihydromyricetin (DMY), dihydromyricetin and transforming growth factor-β1 (DMY+ TGF-β1), transforming growth factor-β1 (TGF-β1) were used as experimental group. Cell proliferation and apoptosis rates were measured by clonal formation and flow cytometry. Transwell invasion and wound healing assay were used to detect cell invasion and migration. The protein expression levels of Caspase-3, Caspase-9, Bcl-2, Bax, Smad2/3, phosphorylation-Smad2/3 (p-Smad2/3) and Vimentin were detected by western blot. Results: The IC₅₀ values of DMY on KYSE410 and KYSE150 cells were 100.51 and 101.27 μmol/L. The clone formation numbers of KYSE150 and KYSE410 in DMY group [(0.53±0.03) and (0.31±0.03)] were lower than those in DMSO group [(1.00±0.10) and (1.00±0.05), P<0.05]. The apoptosis rates of KYSE150 and KYSE410 cells in DMY group [(1.84±0.22)% and (2.80±0.07)%] were higher than those in DMSO group [(1.00±0.18)% and (1.00±0.07)%, P<0.05]. The invasion numbers of KYSE150 and KYSE410 cells in DMY group [(0.42±0.03) and (0.29±0.05)] were lower than those in DMSO group [(1.00±0.08) and (1.00±0.05), P<0.05]. The migration rates of KYSE150 and KYSE410 cells in DMY group [(0.65±0.14)% and (0.40±0.17)%] were lower than those in DMSO group [(1.00±0.10)% and (1.00±0.08)%, P<0.05]. The clone formation numbers of KYSE150 and KYSE410 in TGF-β1 group [(1.01±0.08) and (0.99±0.25)] were higher than those in DMY+ TGF-β1 group [(0.73±0.10) and (0.58±0.05), P<0.05]. The apoptosis rates of KYSE150 and KYSE410 cells in TGF-β1 group [(0.81±0.14)% and (1.18±0.10)%] were lower than those in DMY+ TGF-β1 group [(1.38±0.22)% and (1.85±0.04)%, P<0.05]. The invasion numbers of KYSE150 and KYSE410 cells in TGF-β1 group [(1.19±0.11) and (1.39±0.11)] were higher than those in DMY+ TGF-β1 group [(0.93±0.09) and (0.93±0.05), P<0.05]. The migration rates of KYSE150 and KYSE410 cells in TGF-β1 group [(1.87±0.19)% and (1.32±0.04)%] were higher than those in DMY+ TGF-β1 group [(0.86±0.16)% and (0.77±0.12)%, P<0.05]. The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in DMY group were higher than those in DMSO group, while the protein expression level of Bcl-2 was lower than that in DMSO group (P<0.05). The protein expression levels of p-Smad2/3, Smad2/3 and Vimentin in KYSE150 and KYSE410 cells in DMY group were lower than those in DMSO group (P<0.05). The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in TGF-β1 group were lower than those in DMY+ TGF-β1 group, and the protein expression level of Bcl-2 was higher than that in DMY+ TGF-β1 group (P<0.05). The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in DMY+ TGF-β1 group were lower than those in DMY group, and the protein expression level of Bcl-2 was higher than that in DMY group (P<0.05). The protein expression levels of p-Smad2/3, Smad2/3 and Vimentin in KYSE150 and KYSE410 cells in TGF-β1 group were higher than those in DMY+ TGF-β1 group (P<0.05). Conclusion: DMY can inhibit the proliferation and EMT of ESCC mediated by TGF-β1 and promote cell apoptosis.
Apoptosis ; Caspase 3/metabolism* ; Caspase 9/metabolism* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Dimethyl Sulfoxide/pharmacology* ; Epithelial-Mesenchymal Transition ; Esophageal Neoplasms/metabolism* ; Esophageal Squamous Cell Carcinoma ; Flavonols ; Humans ; Signal Transduction ; Transforming Growth Factor beta1/pharmacology* ; Vimentin/metabolism* ; bcl-2-Associated X Protein/pharmacology*

Objective: A multicenter Chinese mainland survey was conducted to investigate the sensitization distribution characteristics of cat, dog and horse dander in patients with allergic diseases, so as to provide clinicians with epidemiological data of common animal allergens and useful information for the prevention and treatment of allergies in cats, dogs and horses. Methods: The epidemiological investigation and design was adopted. This study is based on the national epidemiological survey of allergic diseases led by the first affiliated Hospital of Guangzhou Medical University. From January to December in 2021, a total of 2 122 patients diagnosed with allergic diseases were included in the outpatient department of respiratory department/pediatrics/allergy department of 14 units such as the First Affiliated Hospital of Guangzhou Medical University, and 222 healthy subjects were included as controls from the physical examination center of the above units in the same period. All the subjects filled out the allergic disease questionnaire under the guidance of doctors, and the allergen-specific immunoglobulin E (sIgE) of cats, dogs and horses of all subjects were detected by magnetic particle chemiluminescence system. The epidemiological characteristics of three animal allergens in different diseases, ages and regions were analyzed. Chi square test was used to analyze the frequency difference between groups, t test or Mann Whitney U test was used to test the distribution difference between two groups, and one-way ANOVA or Kruskal Wallis H test was used to compare the distribution difference between multiple groups. Bar chart, Venn-plot and radar chart were drawn to show the sensitization distribution characteristics. A small number of missing values caused by subjects' omission have been excluded during the analysis. Results: The 2 122 patients with allergic diseases were 57.35% male (1 217/2 122) and 40.95% female (869/2 122), and 1.70% (36/2 122) patients had loss of gender information. The age of patients with allergic diseases was 9.0 (6.0, 28.0) years, while that of healthy controls was 29.0 (13.0, 39.0) years old, and there were 1.7% (36/2 122) and 0.9% (2/222) subjects with missing age information, respectively. The proportion of caesarean section in allergic patients was significantly higher than that in healthy controls (31.4% vs. 17.6%,χ²=16.582,P<0.001) [2.5% (54/2 122) of the patient group and 5.4% (12/222) of the control group had missing birth mode information], and the proportion of patients with allergic diseases who reported that both parents had allergic diseases was significantly higher than that of the control group (35.7% vs. 9.5%, χ²=65.171,P<0.001). Patients with allergic diseases are mainly school-age (6-12 years old) and adolescents (12-18 years old). 16.4% of patients with allergic diseases were sensitized to cat dander, 10% and 6% to dog and horse dander. The sensitization rate of cat dander in patients with rhinitis, asthma, conjunctivitis, food allergy and atopic dermatitis was the highest (16.4%-21.6%), followed by dog dander (10.2%-15.2%). The prevalence of allergic rhinitis was the highest among different animal sensitized populations. The proportion of cat, dog and horse allergens sensitized at the same time is between 10%-15%, and the proportion of any two or more animal dander sensitized at the same time is about 45%. Animal allergens are associated with respiratory allergic diseases, especially allergic rhinitis with allergic conjunctivitis. There were significant differences in the distribution of positive rates of three animal allergens in different regions, and the highest positive rate of cat dander was found in all provinces of the country. Conclusion: The sensitization rate of animal dander allergens increased significantly, and the highest was in children and adolescents. Cat dander is the most common animal allergen, followed by dog. Different animals show obvious cross or common sensitization due to their high homology.
Allergens ; Animals ; Cats ; Cesarean Section ; Dander ; Dogs ; Female ; Horses ; Immunoglobulin E ; Male ; Pregnancy ; Rhinitis, Allergic

To explore the optimal therapy time for the treatment of severe coronavirus disease 2019(COVID-19)by traditional Chinese medicine(TCM)and its influence on the therapeutic effect and prognosis. The clinical data,laboratory findings,and outcomes of 64 patients with severe COVID-19 treated with TCM and western medicine in Chongqing from January 20,2020, to March 11,2020 were retrospectively analyzed.Patients were divided into early intervention group[TCM was initiated within 3 days (including day 3) after the first diagnosis of severe type/critical type COVID-19]and late intervention group[TCM was initiated after 7 days (including day 7) after the first diagnosis of severe type /critical type COVID-19].The changes in clinical parameters during the course of disease were compared between the two groups. On day 14,the oxygenation index was 292.5(252.0,351.0)mmHg in the early intervention group,which was significantly higher than that in the late intervention group [246.0(170.0,292.5)mmHg](=0.005).The length of hospital stay [(18.56±1.11)d (24.87±1.64)d,=0.001],duration of ICU stay [(14.12±0.91)d (20.00±1.53)d,=0.000] and time to negativity [(16.77±1.04)d (22.48±1.66)d,=0.001] in the early intervention group were significantly shorter than those in the late intervention group.The intubation rate(7.3%)in the early intervention group was significantly lower than that in the late intervention group(30.4%)(=0.028). Early TCM therapy within three days after a diagnosis of severe COVID-19 can shorten the length of hospital stay,duration of ICU stay,and time to negativity and decrease intubation rate.
Betacoronavirus ; Coronavirus Infections ; drug therapy ; Humans ; Medicine, Chinese Traditional ; Pandemics ; Pneumonia, Viral ; drug therapy ; Prognosis ; Retrospective Studies

OBJECTIVE: To explore the prognostic factors of elderly AML patients, as well as the application and prognostic value of comprehensive geriatric assessment（CGA） in elderly AML patients in China, so as to determine a suitable comprehensive assessment method that can predict survival and guide treatment of patients in Chinese people. METHODS: Retrospective analysis was performed on the medical records of 84 AML patients aged over 60 years old, and diagnosed in our department from October 2007 to December 2017, and the clinical, pathological and comprehensive evaluation of related prognostic factors was analyzed. RESULTS: The median age of all patients was 70 (60-91) years old, ratio of male to female was 1.9∶1 (55∶29) , the median OS time was 9 (1-125) months, 1 year OS rate was 35.3%, and 5 year OS rate was 12.6%. The age grouping, remission of induction chemotherapy, whether refractory/relapse, WBC count grouping at initial diagnosis, levels of lactate dehydrogenase and creatinine were risk factors for OS. Remission of induction chemotherapy, whether refractory/relapse, WBC count grouping and co-infections at initial diagnosis, levels of lactate dehydrogenase, and ECOG score were the risk factors for DFS. In the assessment of comorbidities, the two score classifications of charlson comorbidity index(CCI) were the risk factor of OS, however,whose effects for DFS were not statistically different. The effects of 3 score classifications of hemaotopoietic cell transplantation comorbidity index (HCT-CI), 4 score classifications of comulative illness kating scale for geriatrics (CIRS-G) and 3 score classifications of CIRS-G on OS and DFS were not statistically different. The impact of the ACA index on OS and DFS was statistically significant in elderly patients. All indexes related with patients self factors and disease-related factors were no independent prognostic factors for OS and DFS, so the judgment of prognosis needs to be comprehensively evaluated. CONCLUSION The prognosis and treatment selection of elderly AML patients should be combined with traditional clinical and pathological prognostic factors as well as comprehensive assessment of the elderly patients.
Aged ; Aged, 80 and over ; China ; Female ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute ; Male ; Middle Aged ; Prognosis ; Remission Induction ; Retrospective Studies

Objective To analyze the tendency of road traffic injuries and explore its main influencing factors in China from 1997 to 2016, so as to provide references for decision-making of prevention and control. Methods Data was collected from national data website. Annual percent change (APC) and average annual percent change (AAPC) were calculated and trend tests were performed by Joinpoint Regression Program 4.6.0.0. Results The overall trend of the indexes was basically the same, reaching the highest record in 2002. The following downward tendency was different and tended to level off after 2009. However, the forecast showed that the fatality of road traffic accidents would increase slightly in recent years. For different road traffic modes, only the average annual percent change of motor vehicle injuries statistically descended (AAPC=-1.83, Z=-2.23, P=0.026). The average annual decreases of non-motor vehicle deaths were statistically significant (AAPC=-1.98, Z=-2.47, P=0.014), and the number of injured showed a notable upward trend instead (AAPC=3.95, Z=5.16, P<0.001). The indexes of walking and riding were declined markedly (AAPC≥7.90, P<0.001). Conclusions The status of walking and riding had been improved significantly, but motor vehicles injuries were still the main traffic mode causing road traffic injuries. The safety situation of non-motor vehicles was increasingly serious. Adopting legal compulsory measures and other intervention to routine systematic management was quite necessary.

Objective: To investigate the efficiency and safety of domestic tyrosine kinase inhibitor (TKI) dasatinib (Yinishu) as second-line treatment for patients with chronic myeloid leukemia in chronic phase (CML-CP). Methods: A retrospective analysis of clinical data of CML-CP patients who received domestic dasatinib as second-line treatment in the CML collaborative group hospitals of Hubei province from March 2016 to July 2018 was performed. The optimal response rate, the cumulative complete cytogenetic response (CCyR), the cumulative major molecular responses (MMR), progression free survival (PFS), event free survival (EFS) and adverse effects (AEs) of the patients were assessed at 3, 6 and 12 months of treatment. Results: A total of 83 CML-CP patients were enrolled in this study. The median follow-up time was 23 months. The optimal response rates at 3, 6 and 12 months in 83 CML-CP patients treated with dasatinib were 77.5% (54/71), 72.6% (61/75) and 60.7% (51/69), respectively. By the end of follow-up, the cumulative CCyR and MMR rates were 65.5% (55/80) and 57.1% (48/73), respectively. The median time to achieving CCyR and MMR was 3 months. During follow-up time, the PFS rate was 94.0% (79/83) and the EFS rate was 77.4% (65/83). The most common non-hematological AEs of dasatinib were edema (32.5%), rash itching (18.1%) and fatigue (13.3%). The common hematological AEs of dasatinib were thrombocytopenia (31.3%), leukopenia (19.3%) and anemia (6.0%). Conclusion: Domestic dasatinib was effective and safe as the second-line treatment of CML-CP patients and it can be used as an option for CML-CP patients.
Antineoplastic Agents ; Dasatinib/therapeutic use* ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Protein Kinase Inhibitors ; Retrospective Studies ; Treatment Outcome

Objective: To evaluate the diagnostic value of bronchoalveolar lavage (BAL) for pulmonary complications in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its safety. Methods: Patients with pulmonary complications after allo-HSCT underwent BAL. Microbiological smears, culture, PCR of CMV-DNA, EBV-DNA and TB-DNA, macro genomes new generation sequencing (mNGS) techniques were performed to detect pathogens in BAL fluid (BALF) . Results: A total of 73 allo-HSCT patients with 86 times of pulmonary complications enrolled this prospective study. They underwent 132 times of BAL procedures. The clinical diagnoses of 88.4% cases were made based on BALF analysis. Of them, 67 cases (77.9%) had infectious pulmonary complications, including 29 cases (33.7%) of fungal infection, 18 cases (20.9%) of mixed infection, 11 cases (12.8%) of viral infection and 9 cases (10.5%) of bacterial infection. The other 9 cases (10.5%) of non-infectious pulmonary complications included 8 cases (9.3%) of idiopathic pneumonia syndrome (IPS) and 1 case (1.2%) of pulmonary infiltration of lymphoma. The diagnoses of the remaining 10 cases (11.6%) were not determined. The platelet counts of 33 patients were less than 50×10(9)/L before BAL. None of them developed severe bleeding complications during or after BAL. Transient fever occurred in 10 patients after BAL. Blood cultures showed staphylococcal bacteremia in them and anti-infection therapies were effective. No life-threatening complications occurred in all of the patients during or after BAL. Conclusion: BALF analysis was informative for the diagnosis of pulmonary complication and safe for patients with pulmonary complications after allo-HSCT.
Bronchoalveolar Lavage ; Bronchoalveolar Lavage Fluid ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Pneumonia/etiology* ; Prospective Studies

Objective To understand the epidemiological characteristics of death cases of echinococcosis in China from 2008 to 2016,so as to provide an important reference for the prevention and control of echinococcosis.Methods The death in-formation registration and management system data were selected to analyze the epidemiological characteristics of the death cas-es of echinococcosis.The data were analyzed by SPSS 21.0 and the map was drawn by ArcGIS 10.1 software.Results From 2008 to 2016,a total of 367 death cases of echinococcosis were reported in China,and the number of deaths in turn was 33,30,21,32,35,54,55,and 81 in each year,with an annual average crude mortality of 129.29/105.The average age of death was(56 ± 18)years;the sex ratio of male to female was 100:94.There was no statistical difference between the male and fe-male death cases(Χ2=0.33,P>0.05).The death cases of echinococcosis were mainly distributed in endemic areas of Qinghai,Sichuan,Ningxia,Xinjiang,Gansu,Inner Mongolia,Yunnan and non-endemic areas of Heilongjiang,Jiangsu,Henan and Shandong.The death cases in the first eleven provinces accounted for 87.5％(321/367)of the total death cases,among which the highest proportions of the nationality,occupation,educational level,highest diagnostic units,and the place of death were Han(52.0％,191/367),farmer(46.6％,171/367),junior high school or below(57.2％,210/367),provincial or three-level hospitals(46.6％,171/367),and at home(59.9％,220/367).Conclusions Since 2014,the death cases of echinococcosis in China have been increasing year by year,indicating that the prevention and treatment of echinococcosis is still very serious.The causes for the rise of the fatality rate remain to be further studied.

OBJECTIVE: Recent studies have indicated the possibility that genistein may improve depression via regulating the expression of miR-221/222. This study is to explore whether genistein could improve depression by altering miR-221/222 levels and investigate the possible mechanisms involved in the improvement effect of genistein. METHODS: The animal model of depression was established through unpredictable chronic mild stress. Nest building test and splash test were adapted to evaluate the effects of genistein on depressive symptoms in mice. qRT-PCR and western blot analysis were used to detect the expression of miR-221/222 and connexin 43 (Cx43) in the prefrontal cortex of the mice. In vitro, U87-MG astrocytes were treated with genistein and the expression of miR-221/222 and Cx43 was measured. The dual-luciferase reporter assay was used to verify whether Cx43 was a direct target of miR-221/222. RESULTS: The behavioral tests showed that genistein could significantly reduce depression symptoms of mice, and this remission was not affected by gender. Genistein in vivo and in vitro could reduce increased levels of miR-221 and miR-222 in the prefrontal cortex of depressed mice, while upregulate Cx43 expression. Dual-luciferase reporter assay suggested Cx43 was directly regulated by miR-221/222 in astrocytes. CONCLUSION: Genistein can play its antidepressant effect through down-regulating miR-221/222 by targeting Cx43.
Animals ; Astrocytes ; Behavior Rating Scale ; Blotting, Western ; Connexin 43* ; Depression* ; Genistein* ; In Vitro Techniques ; Mice ; Models, Animal ; Prefrontal Cortex