BACKGROUND: The brain is a common metastatic site in patients with non-small cell lung cancer (NSCLC), resulting in a relatively poor prognosis. Systemic therapy with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is recommended as the first-line treatment for EGFR -mutated, advanced NSCLC patients. However, intracranial activity varies in different drugs. Thus, brain metastasis (BM) should be considered when choosing the treatment regimens. We conducted this network meta-analysis to explore the optimal first-line therapeutic schedule for advanced EGFR -mutated NSCLC patients with different BM statuses. METHODS: Randomized controlled trials focusing on EGFR-TKIs (alone or in combination) in advanced and EGFR -mutant NSCLC patients, who have not received systematic treatment, were systematically searched up to December 2021. We extracted and analyzed progression-free survival (PFS) and overall survival (OS). A network meta-analysis was performed with the Bayesian statistical model to determine the survival outcomes of all included therapy regimens using the R software. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to compare intervention measures, and overall rankings of therapies were estimated under the Bayesian framework. RESULTS: This analysis included 17 RCTs with 5077 patients and 12 therapies, including osimertinib + bevacizumab, aumolertinib, osimertinib, afatinib, dacomitinib, standards of care (SoC, including gefitinib, erlotinib, or icotinib), SoC + apatinib, SoC + bevacizumab, SoC + ramucirumab, SoC + pemetrexed based chemotherapy (PbCT), PbCT, and pemetrexed free chemotherapy (PfCT). For patients with BM, SoC + PbCT improved PFS compared with SoC (HR = 0.40, 95% CI: 0.17-0.95), and osimertinib + bevacizumab was most likely to rank first in PFS, with a cumulative probability of 34.5%, followed by aumolertinib, with a cumulative probability of 28.3%. For patients without BM, osimertinib + bevacizumab, osimertinib, aumolertinib, SoC + PbCT, dacomitinib, SoC + ramucirumab, SoC + bevacizumab, and afatinib showed superior efficacy compared with SoC (HR = 0.43, 95% CI: 0.20-0.90; HR = 0.46, 95% CI: 0.31-0.68; HR = 0.51, 95% CI: 0.34-0.77; HR = 0.50, 95% CI: 0.38-0.66; HR = 0.62, 95% CI: 0.43-0.89; HR = 0.64, 95% CI: 0.44-0.94; HR = 0.61, 95% CI: 0.48-0.76; HR = 0.71, 95% CI: 0.50-1.00), PbCT (HR = 0.29, 95% CI: 0.11-0.74; HR = 0.31, 95% CI: 0.15-0.62; HR = 0.34, 95% CI: 0.17-0.69; HR = 0.34, 95% CI: 0.18-0.64; HR = 0.42, 95% CI: 0.21-0.82; HR = 0.43, 95% CI: 0.22-0.87; HR = 0.41, 95% CI: 0.22-0.74; HR = 0.48, 95% CI: 0.31-0.75), and PfCT (HR = 0.14, 95% CI: 0.06-0.32; HR = 0.15, 95% CI: 0.09-0.26; HR = 0.17, 95% CI: 0.09-0.29; HR = 0.16, 95% CI: 0.10-0.26; HR = 0.20, 95% CI: 0.12-0.35; HR = 0.21, 95% CI: 0.12-0.39; HR = 0.20, 95% CI: 0.12-0.31; HR = 0.23, 95% CI: 0.16-0.34) in terms of PFS. And, SoC + apatinib showed relatively superior PFS when compared with PbCT (HR = 0.44, 95% CI: 0.22-0.92) and PfCT (HR = 0.21, 95% CI: 0.12-0.39), but similar PFS to SoC (HR = 0.65, 95% CI: 0.42-1.03). No statistical differences were observed for PFS in patients without BM between PbCT and SoC (HR = 1.49, 95% CI: 0.84-2.64), but both showed favorable PFS when compared with PfCT (PfCT vs. SoC, HR = 3.09, 95% CI: 2.06-4.55; PbCT vs. PfCT, HR = 0.14, 95% CI: 0.06-0.32). For patients without BM, osimertinib + bevacizumab was most likely to rank the first, with cumulative probabilities of 47.1%. For OS, SoC + PbCT was most likely to rank first in patients with and without BM, with cumulative probabilities of 46.8%, and 37.3%, respectively. CONCLUSION Osimertinib + bevacizumab is most likely to rank first in PFS in advanced EGFR -mutated NSCLC patients with or without BM, and SoC + PbCT is most likely to rank first in OS.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Afatinib/therapeutic use* ; Lung Neoplasms/metabolism* ; Bevacizumab/therapeutic use* ; Bayes Theorem ; Network Meta-Analysis ; Protein Kinase Inhibitors/therapeutic use* ; Pemetrexed/therapeutic use* ; ErbB Receptors/genetics* ; Brain Neoplasms/genetics* ; Mutation/genetics*

OBJECTIVE To investigate the mechanism of Mayuan tongbian zhitong decoction on improving slow-transmission constipation（STC）in rats by regulating AMP activated protein kinase （AMPK）/endothelial nitric oxide synthase （eNOS）signaling pathway. METHODS The rats were randomly divided into blank group ，model group ，Mayuan tongbian zhitong decoction low-dose，medium-dose and high-dose groups （6，12，18 mg/kg），with 10 rats in each group. Except for blank group ，other groups were given Compound diphenoxylate suspension to induce STC model. After modeling ，blank group and model group were given normal saline intragastrically ，and Mayuan tongbian zhitong decoction groups were given relevant medicine intragastrically ， once a day ，for consecutive 2 weeks. The number of feces and water content of feces in each group were observed before and after treatment；the carbon powder propulsion rate of rats in each group was calculated ；the pathological structure of colon in each group was observed ；the levels of nitric oxide （NO）and nitric oxide synthase （NOS）in colon tissues of rats in each group were detected；the expressions of AMPK ，eNOS，mammalian target of rapamycin （mTOR），tuberous sclerosis complex 1（Tsc-1）， Tsc-2 and eukaryotic promoter 4E binding protein （4ebp）were also detected. The active ingredients of Cannabis sativa ，Citrus aurantium and Rehmannia glutinosa were screened from Mayuan tongbian zhitong decoction. The active ingredients with high Degree value were docked with AMPK and eNOS ，to verify the interaction. RESULTS Compared with before treatment ，the number and water content of feces were increased significantly in Mayuan tongbian zhitong decoction groups （P＜0.05）. Compared with blank group ，carbon powder propulsion rate of model group was decreased significantly （P＜0.05）； colonic structure was disordered ，and a large number of inflammatory cells were seen in submucosa ；the levels of NO and NOS in colon tissue as well as the protein expressions of AMPK ，eNOS，mTOR，Tsc-1，Tsc-2 and 4ebp were increased significantly （P＜0.05）. Compared with model group ，above indexes of Mayuan tongbian zhitong decoction groups （except for NOS in low-dose group ）were reserved significantly （P＜0.05）. In the molecular docking experiment ，the active components with the highest Degree values in C. sativa ，C. aurantium and R. glutinosa were（Z）-3-（4-hydroxy-3-methoxy-phenyl）-N-[2-（4-hydroxyphenyl）ethyl] acrylamide，nobiletin and stigmasterol. The binding energies of AMPK with these three components were －5.15，－4.61 and －4.83 kJ/mol，the binding energies of eNOS with these three components were －6.11，－5.40 and －5.91 kJ/mol. The conformations of these three compounds with AMPK and eNOS were stable and their binding activities were high. CONCLUSIONS Mayuan tongbian zhitong decoction can improve the constipation symptoms and intestinal function in STC model rats ，and its specific mechanism may be related to the inhibition of AMPK/eNOS signaling pathway.

Objective:To identify the key genes for neuropathic pain in rats.Methods:The genomic data of spinal cord tissues of rats (GSE18803) were downloaded from the Gene Expression Database at the American Center for Biotechnology Information to identify differentially expressed genes associated with neuropathic pain, and key genes were obtained by further analysis of the protein-protein interaction networks.Single-cell localization and expression of the key genes were analyzed by the Tabula Muris database.Results:The protein-protein interaction networks identified 10 hub genes, including Tyrobp, Clec4a3, C1qc, Ptprc, Laptm5, Csf1r, C1qa, C1qb, Fcgr3a, Cd53. Cd53, Laptm5 and Ptprc were mainly expressed in macrophages, B cells, NK cells, monocytes and granulocytes. Clec4a3 and Csf1r were mainly expressed in monocytes, Fcgr3a in monocytes and granulocytes, and Tyrobp in macrophages, monocytes, granulocytes, and pluripotent progenitor cells. Conclusions:Ten target genes associated with neuropathic pain are identified using bioinformatics, and their distribution and expression in immune inflammatory cells are obtained through comprehensive analysis.

Objective:To evaluate the role of nucleotide-binding oligomerization domain-2 (NOD2) in dorsal root ganglion in the development of neuropathic pain (NP) in rats.Methods:Thirty-two adult male SPF Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, were divided into 4 groups ( n=8 each) using a random number table method: control group (group C), NP group (group S), negative control siRAN group (group N), and NOD2-siRNA group (group R). In N and R groups, 1×10 8 IFU/ml negative control siRNA and NOD2-siRNA 10 μl were intrathecally injected, respectively, once a day for 3 consecutive days.Normal saline 10 μl was intrathecally injected once a day for 3 consecutive days in C and S groups.The model of NP was established using spared nerve injury (SNI) at 2 weeks after intrathecal injection.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before surgery and 1, 3, 7, 10, 14 and 28 days after SNI.Animals were sacrificed after measuring pain threshold on day 28, and the dorsal root ganglions (DRGs) of the lumbar segment (L 4-6) were removed for determination of the expression of NOD2 (by Western blot) and expression of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), IL-6 and NOD2 mRNA (using quantitative real-time polymerase chain reaction). Results:Compared with group C, MWT was significantly decreased at each time point after SNI, and the expression of NOD2 protein and mRNA and TNF-α, IL-1β and IL-6 mRNA in DRGs was up-regulated in group NP ( P<0.01). Compared with group NP, MWT was significantly increased at each time point after SNI, and the expression of NOD2 protein and mRNA and TNF-α, IL-1β and IL-6 mRNA in DRGs was down-regulated in group R ( P<0.01), and no significant change was found in the parameters mentioned above in group N ( P>0.05). Conclusion:The mechanism underlying the development of NP may be related to the up-regulation of NOD2 expression in DRGs, thus further promoting the expression of pro-inflammatory factors in rats.

Objective: To compare the effect of different orthokeratology lenses in controlling the progression of low myopia in children, and to provide a reference for exploring effective prevention measures for eyesight of children. Methods: A total of 175 cases (350 eyes) aged 8-12 years old who were fitted with orthokeratology lenses were collected in this retrospective study. The differences in the changes of the axis length (AL) and the spherical equivalent refraction (SER) were analyzed after wearing different orthokeratology lenses for one year, and the relationship between the change of AL, SER and gender, age was also analyzed. Results: In the Mouldway group, Alpha group, Lucid group and CRT group, the Median ( P 25 , P 75 ) of AL changes were 0.23 ( 0.12 , 0.41), 0.30 (0.17, 0.45), 0.35 (0.16, 0.41) and 0.33 (0.23, 0.41)mm, and there were no statistical significant difference between four groups ( Z =7.70, P >0.05); The Median ( P 25 , P 75 ) of SER changes were -0.31 (-1.00, 0.28), -0.38 ( -1.22 , 0.13), -0.25 (-0.84, 0.13) and -0.63 (-1.13, 0.25)D, and there were no statistical significant difference between four groups ( Z =2.15, P >0.05). The age had negative correlation with the change of AL ( r =-0.26, P <0.05), but has nothing to do with the change of SER ( r =0.10, P >0.05). There was no statistically significant difference in the change of AL ( Z =2.25, P > 0.05 ) and SER ( Z =-1.50, P >0.05) among children of different genders. Conclusion Different orthokeratology lenses have no differences in controlling the growth of the AL and changing the SER.

With continuous discovery of tumor immune targets and continuous changes in antibody research and development technology, antibody drugs are becoming more and more widely used in clinical practice. However, some targets are not only expressed on tumor cells, but also on red blood cells. Therefore, the clinical application of antibodies against the corresponding targets may interfere with the detection of blood transfusion compatibility, resulting in difficulty in blood matching or delay of blood transfusion. This consensus summarizes the current solutions for the interference of CD38 monoclonal antibody (CD38 mAb) in transfusion compatibility testing. After analyzing the advantages and disadvantages of different methods, polybrene and sulfhydryl reducing agents [dithiothreitol (DTT) or 2-mercaptoethanol (2-Me)], as a solution for CD38 mAb interference in blood compatibility testing, are recommended for Chinese patients, so as to eliminate blood transfusion interference produce by CD38 mAb and further provide a pre-transfusion workflow for clinicians and technicians in Department of Blood Transfusion.

Objective:To explore the characteristics of cognitive function in patients with early onset and adult onset schizophrenia.Methods:In this cross-sectional study, 546 patients with schizophrenia who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-Ⅳ) were selected.Among them, 62 cases were defined as early onset schizophrenia (EOS, age of onset＜18 years) and 175 patients were defined as adult onset schizophrenia (AOS, age of onset≥25 years).Patients underwent clinical assessments with the Positive and Negative Symptom Scale (PANSS) and the Personal and Social Performance Scale (PSP), and comprehensive neuropsychological assessments.Results:The EOS patients got lower scores in motor function-PEGDOM T score [ (26±12) vs. (30±11), P＜0.01], working memory-average T score of PASAT and WMSSP[ (34±12) vs. (38±10), P＜0.05]and executive function (inhibition) -Stroop T score [ (35±12) vs. (39±10), P＜0.05]than AOS patients.No differences were fund in processing speed, verbal memory and learning, visual memory and learning (Ps＞0.05) between the two groups.Conclusion:It suggests that the EOS patients have worse motor function, working memory and inhibition.

PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. MATERIALS AND METHODS: Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP-14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. RESULTS: Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. CONCLUSION: R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.
Asian Continental Ancestry Group ; B-Lymphocytes ; Cyclophosphamide ; Disease-Free Survival ; Doxorubicin ; Follow-Up Studies ; Humans ; Lymphoma, B-Cell ; Prednisone ; Prognosis ; Rituximab ; Vincristine

Objective: To understand the dyslipidemia rate and trend of blood lipid level in an urban community in Hangzhou. Methods: A total of 1 485 urban community residents aged 24 years or older who had participated in health checkup over 6 years, from 2011-2016, were selected by random cluster sampling. Fasting blood Triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) levels were measured in all subjects. A χ² test was used to analyze the dyslipidemia rate trend, and an ANOVA of repeated measurement was conducted to observe the blood lipid level changes. Results: From 2011 to 2016, the total abnormal rates of blood lipids in 1 485 residents were 33.2% (493/1 485), 30.5% (453/1 485), 30.4% (452/1 485), 26.5% (394/1 485), 26.3% (391/1 485), and 25.1% (373/1 485), respectively, which showed a declining trend year-by-year (χ²=36.051, P<0.01). Among these results, however, the high TG rate did not significantly differ from year-to-year (χ²=10.081, P>0.05). The TG, TC, LDL-C, and HDL-C levels statistically differed over the 6 years (F=4.876, 33.033, 170.254, 58.442, respectively, all P<0.01). LDL-C was the highest in 2011 [(3.02±0.29) mmol/L] and the lowest in 2016 [(2.72±0.71) mmol/L], while HDL-C was the highest in 2016 (1.44±0.33 mmol/L) and the lowest in 2011 [(1.35±0.30) mmol/L]. Time-sex group interaction effect analysis: TC and HDL-C levels showed different trends over time between men and women (F=2.556, 4.982, respectively, all P<0.05), and the TC level in the male group was significantly lower than in the female group, since 2012. Interaction effect of time age group: TC and LDL-C levels showed different trends between age groups over time, and the declining trend of TC and LDL-C in the elderly group was more significant than in the young or middle age group (F=10.328, 3.085, respectively, all P<0.01). Conclusions The community population showed an overall improvement in blood lipid levels; however, there was no significant improvement in high TG levels. It is necessary to continue monitoring blood lipid levels in the community, especially to strengthen the prevention and control of high TG levels.

Objective:To investigate the correlation between plexinC1 (PLXNC1) rs2272335 polymorphism and the family clus-tering genetic susceptibility to primary liver cancer (PLC) in Guangxi and the expression of PLXNC1. Methods:Genotype and alleles of rs2272335 were determined in 20 liver cancer family groups (79 cases) and 10 healthy normal control groups (40 cases) in Fusui County through Time of Flight Mass Spectrometer. Immunohistochemistry detected the PLEXNC1 protein expression. Results:For the alleles of PLXNC1 (rs2272335) site, the risk of hepatocellular carcinoma (HCC) for individuals with [C] allele was 4.16-fold (95%CI=0.37-47.3, P=0.032) compared with that for individuals with [T] allele among the members of the healthy normal control group. The fre-quencies of the [C] and [T] alleles were similar in the HCC patients and the core individuals of liver cancer families (P>0.05). For the genotype of the PLXNC1 (rs2272335) site, the differences in frequencies of TT, TC, and CC genotypes were not statistically significant among the PLC patients and the core individuals of the liver cancer families and normal controls. The PLXNC1 protein expression in HCC (3.12±1.12) was higher than in hepatocellular paracancerous tissues (1.54±0.67) and in benign hepatocellular lesions (1.23±0.87) (P<0.05). Conclusion:The [C] allele of PLXNC1 (rs2272335) site might be the risk gene for the occurrence of PLC family clustering in Guangxi. PLXNC1 protein overexpression was closely correlated with PLC oncogenesis.