Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, most NSCLC patients are at advanced stage at the time of diagnosis. For patients without sensitive driven-oncogene mutations, chemotherapy is still the main treatment at present, the overall prognosis is poor. Improving outcomes and obtaining long-term survival are the most urgent needs of patients with advanced NSCLC. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs), especially targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have made a breakthrough in the treatment of NSCLC, beneficial to patients' survival and changed the treatment pattern for NSCLC. It shows more and more important role in the treatment of NSCLC. Led by NSCLC expert committee of Chinese society of clinical oncology (CSCO), relevant experts in this field were organized. On the basis of referring to domestic and foreign literature, systematically evaluating the results of Chinese and foreign clinical trials, and combining the experiences of the experts, the experts group reached an agreement to develop this consensus. It will guide domestic counterparts for better application of ICIs to treat NSCLC.

OBJECTIVE: To investigate the potential antifibrotic mechanisms of Chinese medicine Ganshuang Granules (, GSG) and to provide clinical therapeutic evidence of its effects. METHODS: A cirrhotic mouse model was established by intraperitoneally injecting a mixture of CCl (40%) and oil (60%) at 0.2 mL per 100 g of body weight twice a week for 12 weeks. After 12-week modeling, GSG was intragastric administrated to the mice for 2 weeks, and the mice were divided into low-, medium- and high-dose groups at doses of 1, 2 and 4 g/(kg·day), respectively. Liver morphology changes were observed using Masson's trichrome staining and B-ultrasound. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hyaluronic acid (HA) in serum were detected using an automatic biochemistry analyzer. The expressions of desmin, smooth muscle actin (SMA) and Foxp3 in liver were detected by immunoflfluorescence. The regulatory T cell (Treg) frequency was determined through flflow cytometry analysis. Collagen-I, SMA, IL-6, tumor necrosis factor α (TNF-α), interleukin (IL)-1β and transforming growth factor β1 (TGF-β1) expression levels were measured using quantitative polymerase chain reaction (qPCR). RESULTS: Masson's staining result showed fewer pseudolobule structures and fibrous connective tissue in the GSG-treatment groups than in the spontaneous recovery group. Ultrasonography showed that GSG treatment reduced the number of punctate hyperechoic lesions in mice cirrhotic livers. The serum ALT, AST, HA levels were significantly ameliorated by GSG treatment (ALT: F=8.104, P=0.000; AST: F=7.078, P=0.002; and HA: F=7.621, P=0.001). The expression levels of collagen-I and SMA in the cirrhotic livers were also attenuated by GSG treatment (collagen-I: F=3.938, P=0.011; SMA: F=4.115, P=0.009). Tregs, which were elevated in the fibrotic livers, were suppressed by GSG treatment (F=8.268, P=0.001). The expressions of IL-6, TNF-α and IL-1β increased, and TGF-β levels decreased in the cirrhotic livers after GSG treatment (IL-6: F=5.457, P=0.004; TNF-α: F=6.023, P=0.002; IL-1β: F=6.658, P=0.001; and TGF-β1: F=11.239, P=0.000). CONCLUSIONS GSG promoted the resolution/regression of cirrhosis and restored liver functions in part by suppressing Treg cell differentiation, which may be mediated by hepatic stellate cells.
Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hepatic Stellate Cells ; drug effects ; Liver Cirrhosis, Experimental ; drug therapy ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; T-Lymphocytes, Regulatory ; drug effects

OBJECTIVE: To study the significance of plasma neutrophil extracellular trap (NET) and its markers in the diagnosis of community-acquired pneumonia (CAP) in children. METHODS: A total of 160 children with CAP were enrolled as the CAP group, and 50 healthy children were enrolled the control group. According to disease severity, the CAP group was further divided into a mild CAP subgroup with 137 children and a severe CAP subgroup with 23 children. According to the pathogen, the CAP group was further divided into a bacterial pneumonia subgroup with 78 children, a Mycoplasma pneumonia subgroup with 35 children, and a viral pneumonia subgroup with 47 children. The levels of plasma NET and its markers [antibacterial peptide (LL-37), extracellular free DNA (cfDNA), and deoxyribonuclease I (DNase I)] were measured. Receiver operating characteristic (ROC) curve was used to analyze the value of each index in diagnosing CAP and assessing its severity. RESULTS: Compared with the control group, the CAP group had significant increases in the levels of NET, LL-37, and cfDNA and a significant reduction in the activity of DNase I (P<0.05). Compared with the mild CAP subgroup, the severe CAP subgroup had significantly higher levels of NET, LL-37 and cfDNA and a significantly lower activity of DNase I (P<0.05). There were no significant differences in the levels of NET, LL-37, and cfDNA and the activity of DNase I among the bacterial pneumonia, Mycoplasma pneumonia, and viral pneumonia subgroups (P>0.05). In the CAP group, plasma NET levels were positively correlated with white blood cell count (WBC), percentage of neutrophils, and serum levels of C-reactive protein (CRP), procalcitonin and tumor necrosis factor-α (r=0.166, 0.168, 0.275, 0.181 and 0.173 respectively, P<0.05); LL-37 and cfDNA levels were positively correlated with WBC (r=0.186 and 0.338 respectively, P<0.05) and CRP levels (r=0.309 and 0.274 respectively, P<0.05); the activity of DNase I was negatively correlated with CRP levels (r=-0.482, P<0.05). The ROC curve analysis showed that NET, LL-37, cfDNA, and DNase I had an area under the ROC curve (AUC) of 0.844, 0.648, 0.727, and 0.913 respectively in the diagnosis of CAP, with optimal cut-off values of 182.89, 46.26 ng/mL, 233.13 ng/mL, and 0.39 U/mL respectively, sensitivities of 88.12%, 35.63%, 54.37%, and 91.25% respectively, and specificities of 74.00%, 92.00%, 86.00%, and 76.00% respectively. In the assessment of the severity of CAP, NET, LL-37, cfDNA, and DNase I had an AUC of 0.873, 0.924, 0.820, and 0.778 respectively, with optimal cut-off values of 257.7, 49.11 ng/mL, 252.54 ng/mL, and 0.29 U/mL respectively, sensitivities of 83.21%, 86.96%, 78.26%, and 95.65% respectively, and specificities of 78.26%, 83.94%, 76.64%, and 56.93% respectively. CONCLUSIONS Plasma NET and its related markers have a certain value in diagnosing CAP and assessing its severity in children.
Biomarkers ; C-Reactive Protein ; Child ; Community-Acquired Infections ; diagnosis ; Early Diagnosis ; Extracellular Traps ; Humans ; Pneumonia ; ROC Curve

OBJECTIVE: To compare the effects of electroacupuncture (EA) at "Zusanli" (ST 36) versus "Yanglingquan" (GB 34) in the pregnant rats on perinatal nicotineexposureinduced lung function and morphology of newborn rats and explore the rule of acupoint effect in EA for the prevention from lung dysplasia in newborn rats. METHODS: A total of 24 female SD rats were randomized into a normal saline group (S group), a nicotine group (N group), a nicotineST 36 group (N + ST 36 group) and a nicotineGB 34 group (N+GB 34 group), 6 rats in each one. Starting at the 6th day of pregnancy, 0.9% sodium chloride solution was injected subcutaneously in the S group, 1 mg/kg; and in the rest 3 groups, nicotine of the same dose was injected through to the 21st postnatal day to establish the perinatal nicotineexposure model. Simultaneously, during model preparation, EA was applied at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) in the N+ST 36 group and the N+GB 34 group respectively, once a day, through to the 21st postnatal day. The lung function analytic system for small animal was adopted to observe the changes in lung function indicators in newborn rats, such as peak inspiratory flow (PIF), peak expiratory flow (PEF), expiratory resistance (RE), inspiratory resistance (RI) and dynamic compliance (Cdyn). HE staining was used to observe the morphological changes of lung, such as alveolar fusion and rupture. RESULTS: Compared with the S group, PEF and Cdyn were lower and PIF, RI and RE higher in the N group (all <0.01), additionally, alveoli were fused and ruptured, alveolar wall thickened, the numbers of alveoli reduced, the interspace of alveoli enlarged and the diameter increased (<0.01). Compared with the N group, in the N+ST 36 group, PEF and Cdyn were increased, PIF, RI and RE reduced (<0.05, <0.01), the alveolar fusion and rupture relieved, the numbers of alveoli increased, alveolar wall thinner, the interpsace of alveoli became normal and the diameter was reduced significantly (<0.01). In the N+GB 34 group, the changes of lung function and morphological indicators were not significant (>0.05). CONCLUSION Electroacupuncture at "Zusanli" (ST 36) in the pregnant rats significantly improves the perinatal nicotineexposureinduced lung function and morphology of newborn rats than electroacupuncture at "Yanglingquan" (GB 34).
Acupuncture Points ; Animals ; Animals, Newborn ; Electroacupuncture ; Female ; Lung ; drug effects ; physiopathology ; Nicotine ; toxicity ; Pregnancy ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Objective: To analyze the status of domestic surgical treatment of synchronous peritoneal carcinomatosis from colorectal cancer in China. Methods: Clinicopathological data of patients who underwent surgery from October 2003 to October 2018 in 16 domestic medical centers was retrospectively analyzed. Excel database was created which covered 77 fields of 7 parts: baseline information of patients, laboratory tests, imaging tests, chemoradiotherapy information, intra-operative findings, postoperative pathology and follow-up data. The Wilcoxon rank-sum test was used for comparison of the measurement data between groups. The χ² test was used for comparison of the categorical data between groups. The survival curve was calculated by the Kaplan-Meier method. Results: Of the 1 003 patients, there were 575 male and 428 female patients with the age of (58.5±14.1) years (range: 18 to 92 years). In a total of 920 patients, the carcinoma of sigmoid colon was performed in 292 cases (31.8%) with the highest ratio. The proportion of patients with liver metastasis and lung metastasis were 27.9% (219/784) and 8.3% (64/769). Preoperative detection of carcino-embryonic antigen level was the most common method in China (87.74%, 880/1 003), and the positive rate was 64.5% (568/880). The correct rate of preoperative imaging tests was 40.7% (280/688). The ratio of peritoneal carcinomatosis index (PCI) scores between 0 and 10 was the highest (59.6%, 170/285). Two hundred and sixty-two (27.0%) patients were performed by totally laparoscopic operation in 971 patients. The resection of primary tumor was performed in 588 of the 817 patients (72.0%). In a total of 457 cases, 253 (55.4%) patients were performed cytoreduction which group scored completeness of cytoreduction (CCR) 0. The postoperative hyperthermic intraperitoneal chemotherapy was implemented in 70 of the 334 cases (21.0%). Among 1 003 cases, 562 cases (56.03%) had complete follow-up data and the median overall survival was 15 months. The primary tumor resection and the CCR scores were affected by the PCI scores. The patients underwent primary tumor resection (187/205 vs. 26/80, χ²=105.085, P=0.000) and the patients were performed cytoreduction which scored CCR 0 or CCR 1 (162/204 vs. 8/78, Z=-10.465, P=0.000) had significant difference between the groups of PCI<20 and ≥20. There was a close correlation between the surgical method and the CCR scores (Z=-3.246,P=0.001).When the maximum degree of tumor reduction was planned, most surgeons would choose laparotomy. The overall survival time was longer in patients with primary tumor resection (P=0.000). The median survival time was 18.6 months in the group of primary tumor resection. Conclusions It is difficult to diagnose the synchronous peritoneal carcinomatosis from colorectal cancer before the operation. Primary tumor resection has an obvious effect to prolong the survival time. It is necessary to standardize the treatment of peritoneal metastasis.

OBJECTIVETo explore expression and significance of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and survivin in acute lymphoblastic leukemia (ALL).

METHODSPeripheral blood samples were collected from 68 patients with ALL in our hospital including 48 newby diagnosed patients, 13 patients in remission, 7 patients in relapse, and 20 healthy volunteers (control). The expressions of PTEN and survivin mRNA and protein were detected by real time PCR, Western blot and respectively, and clinical pathological parameter was analyzed.

RESULTSThe expressions of PTEN mRNA and protein in newby diagnosed, remission and relapsed group were lower than that in control group (P<0.01). The expressions of PTEN mRNA and protein in newly diagnosed and relapsed groups were lower than that in remission group (P<0.01). The expressions of survivin mRNA and protein in newly diagnosed, remission and relapsed group were higher than that in control group (P < 0.01). The expressions of survivin mRNA and protein in newly diagno sed and relapsed groups were higher than that in remission group (P < 0.01). The expressions of PTEN and survivin mRNA did not relahed with the age, sex and white blood count in ALL patients, and also did not related with the morphological classification in newly diagnosed ALL (P>0.05), but related with immunological calssification in newly diagnosed ALL (P < 0.01). The expressions of PTEN and survivin were negatively correlated in ALL (P < 0.01).

CONCLUSIONPTEN and survivin play an important role in the occurrence, development and prognosis in ALL, and may be one of the potential targets for ALL treatment.

OBJECTIVETo investigate the expression of CD160 on the surface of human natural killer (NK) cells and its possible relationship with hematological malignancies.

METHODSCD160 expression on human leukemia cell line NK92 cells was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The proliferation characteristics and cell surface markers of this cell line were determined. Cytotoxicity of NK92 against 2 human myeloid leukemia cell lines, K562 and THP-1 was analyzed ex vivo. CD160 blocking antibody CL1-R2 was employed to clarify its role in NK cell mediated cytolysis. Then, the expression of CD160 on NK cells in peripheral blood from various patients with hematological malignancies were measured by flow cytometry.

RESULTSThe mRNA and protein levels of CD160 expressions on NK92 cells were confirmed by RT-PCR and Western blot, respectively. The flow cytometry results demonstrated that the strong positive expression of CD160 could be detected on the NK92 cell surface. NK92 could effectively kill K562 and THP-1 cells, while the cytolysis effect was abrogated in the presence of CD160 blocking antibody CL1-R2. The high levels of HVEM were expressed on both target cells, but the HLA class I molecules were absent on K562. The expression of CD160 on CD3CD56 NK cells in peripheral blood from patients with acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients was significant lower than that in the normal controls (P<0.05).

CONCLUSIONThe cytolysis function of human NK cells is mediated partially by CD160 molecule. The decrease of CD160 expression on NK cells from patients with various hematological malignancies implies that down-regulation of CD160 expression may be a novel mechanism of tumor immune escape.

BACKGROUNDWhite matter lesions (WMLs) are common findings in brain magnetic resonance imaging (MRI) and are strongly associated with stroke incidence, recurrence, and prognosis. However, the relationship between WMLs and transient ischemic attacks (TIAs) is not well established. This study aimed to determine the clinical significance of WMLs in patients with TIA.

METHODSA total of 181 consecutive inpatients with first-ever TIA were enrolled. Brain MRIs within 2 days of symptom onset were used to measure WML volumes. Recurrent vascular events within 1 year of TIA onset were assessed. The relationship between WMLs and recurrent risk of vascular events was determined by a multivariate logistic regression.

RESULTSWMLs were identified in 104 patients (57.5%). Age and ratio of hypertension were significantly different between patients with and without WMLs. The incidence of vascular events in patients with WMLs significantly increased in comparison to those without WMLs (21.15% vs. 5.19%, 95% confidence interval [CI]: 1.18-15.20, P = 0.027) after controlling for confounders. Furthermore, distributions of WML loads were found to be different between patients who developed vascular events and those who did not. WML volumes were demonstrated to be correlated with recurrent risks, and the fourth quartile of WML volumes led to an 8.5-fold elevation of recurrent risk of vascular events compared with the first quartile (95% CI: 1.52-47.65, P = 0.015) after adjusting for hyperlipidemia.

CONCLUSIONWMLs occur frequently in patients with TIA and are associated with the high risk of recurrent vascular events, suggesting a predictive neuroimaging marker for TIA outcomes.

Chinese medicine Buyang Huanwu decoction (BYHW) is widely used in treating cerebral infarction combined with Qi-deficiency and blood-stasis syndrome, but the pharmacological basis is still not clear. This study aims to uncover the biological basis of BYHW therapy for cerebral infarction combined with Qi-deficiency and blood-stasis syndrome using label-free proteomic technology. Using Qi deficiency and blood stasis rat cerebral infarction model as the research object, the protein expression of rat brain tissue was compared among the sham operation group, the model group and the drug group. Quantitative analysis of the 3 groups of tissue samples detected 3 959, 3 996 and 4 055 proteins in the sham operation group, the model group and the drug group, respectively. Take model group as the control group, 391 proteins were identified to be upregulated or downregulated for more than 2 folds. Biological analysis and functional enrichment of the differentially expressed proteins revealed that BYHW may treat cerebral infarction combined with Qi-deficiency and blood-stasis syndrome through energy metabolism, nervous system and several signal pathways. This study preliminarily revealed the pharmacological mechanism of BYHW at the protein level, and provided a molecular basis for clinical treatment and traditional Chinese medicine research on cerebral infarction combined with Qi-deficiency and blood-stasis syndrome.

Adult ; China ; Databases, Factual ; Female ; Humans ; Male ; Middle Aged ; Pituitary Diseases ; classification ; epidemiology ; Registries ; Software