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BACKGROUND@#Immune checkpoint inhibitors (ICIs) are standard treatments for advanced non-small cell lung cancer (NSCLC); however, evidence regarding their relative efficacy and safety is lacking. This study compared the efficacy and safety of all currently available ICI treatments in patients with advanced NSCLC to identify optimal treatment regimens.@*METHODS@#PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase databases were systematically searched for randomized controlled trials (RCTs) published up to August 8, 2022. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included objective response rate (ORR) and adverse events (AEs).@*RESULTS@#Forty RCTs involving 22,526 patients were selected, and a total of 26 treatment regimens were identified. Treatment with anti-programmed cell death protein-1 (anti-PD-1) provided superior OS compared with anti-programmed death ligand 1 (anti-PD-L1) treatment. ICIs plus platinum-based chemotherapy (PBC) were superior to ICIs treatment alone, although the addition of PBC increased treatment toxicity. Cemiplimab ranked first for OS and lowest for any-grade AEs in advanced NSCLC patients without PD-L1 selection. Regarding grade ≥3 AEs, the toxicity of ICI monotherapy or ICI-ICI combination was consistently lower than that of the other treatments. For patients without PD-L1 selection, cemiplimab showed the best OS, pembrolizumab plus docetaxel (Pem-DXT) showed the best PFS, and atezolizumab plus bevacizumab and PBC (Atezo-Beva-PBC) showed the best ORR. Pembrolizumab plus PBC and Atezo-Beva-PBC were the most likely optimal treatments for OS and PFS in patients with PD-L1 expression <1%, respectively. In patients with PD-L1 expression ≥1%, treatment regimens containing anti-PD-1 provided superior OS benefits compared with those of anti-PD-L1 treatment, and sintilimab plus PBC (Sint-PBC) provided the best OS benefit; as for PFS, ICI plus PBC consistently showed greater PFS benefits than ICI or PBC alone. For patients with anti-PD-L1 expression of 1-49%, camrelizumab plus PBC provided the best benefit for OS and PFS among included treatment. Durvalumab-tremelimumab-PBC and Atezo-Beva-PBC respectively presented the highest OS and PFS for patients with PD-L1 expression ≥50%. Moreover, cemiplimab and Atezo-Beva-PBC yielded the best OS and PFS benefits as first-line treatments for patients with advanced NSCLC, respectively.@*CONCLUSIONS@#Although ICI plus PBC likely resulted in superior survival outcomes compared to ICI treatment alone, it did increase toxicity. Cemiplimab presented a well-balanced efficacy and safety profile in advanced NSCLC treatment. Our findings with the current ICIs comparisons will aid future trials for cancer immunotherapy.@*REGISTRATION@#PROSPERO, https://www.crd.york.ac.uk/PROSPERO/ , CRD42022323879.
Subject(s)
Humans , Immune Checkpoint Inhibitors/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Network Meta-Analysis , Lung Neoplasms/drug therapyABSTRACT
Objective To investigate the prevalence of single nucleotide polymorphisms (SNPs) of artemisinin resistance-related Pfubp1 and Pfap2mu genes in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea, so as to to provide baseline data for the formulation of malaria control strategies in Bioko Island. Methods A total of 184 clinical blood samples were collected from patients with P. falciparum malaria in Bioko Island, Equatorial Guinea from 2018 to 2020, and genomic DNA was extracted. The Pfubp1 and Pfap2mu gene SNPs of P. falciparum were determined using a nested PCR assay and Sanger sequencing, and the gene sequences were aligned. Results There were 159 wild-type P. falciparum isolates (88.83%) from Bioko Island, Equatorial Guinea, and 6 SNPs were identified in 20 Pfubp1-mutant P. falciparum isolates (11.17%), in which 4 non-synonymous mutations were detected, including E1516G, K1520E, D1525E, E1528D. There was only one Pfubp1gene mutation site in 19 Pfubp1-mutant P. falciparum isolates (95.00%), in which non-synonymous mutations accounted for 68.42% (13/19). D1525E and E1528D were identified as major known epidemic mutation sites in the Pfubp1 gene associated with resistance to artemisinin-based combination therapies (ACTs). At amino acid position 1525, there were 178 wild-type P. falciparum isolates (99.44%) and 1 mutant isolate (0.56%), with such a mutation site identified in blood samples in 2018, and at amino acid position 1528, there were 167 wild-type P. falciparum isolates (93.30%) and 12 mutant isolates (6.70%). The proportions of wild-type P. falciparum isolates were 95.72% (134/140), 79.25% (126/159) and 95.83% (161/168) in the target amplification fragments of the three regions in the Pfap2mu gene (Pfap2mu-inner1, Pfap2mu-inner2, Pfap2mu-inner3), respectively. There were 16 different SNPs identified in all successfully sequenced P. falciparum isolates, in which 7 non-synonymous mutations were detected, including S160N, K199T, A475V, S508G, I511M, L595F, and Y603H. There were 7 out of 43 Pfap2mu-mutant P. falciparum isolates (16.28%) that harbored only one gene mutation site, in which non-synonymous mutations accounted for 28.57% (2/7). For the known delayed clearance locus S160N associated with ACTs, there were 143 wild-type (89.94%) and 16 Pfap2mu-mutant P. falciparum isolates (10.06%). Conclusions Both Pfubp1 and Pfap2mu gene mutations were detected in P. falciparum isolates from Bioko Island, Equatorial Guinea from 2018 to 2020, with a low prevalence rate of Pfubp1 gene mutation and a high prevalence rate of Pfap2mu gene mutation. In addition, new mutation sites were identified in the Pfubp1 (E1504E and K1520E) and Pfap2mu genes (A475V and S508G).
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Objective To investigate the relationship between Plasmodium infection and platelet factor Ⅳ(PF4) and to provide the ideas for the treatment of malaria.Methods The serum PF4 concentration was determined with the Enzyme-linked immunosorbent assay (ELISA) in the malaria group (122 cases of malaria patients)and the control group (399 cases of normal).The average value (mean) and positive rate of PF4 were compared between two groups.Results The PF4 level of malaria group was significantly higher than that in the control group and the difference between two groups was statistical significance (P ＜ 0.05).There was no significant difference in Plasmodium falciparum density between the PF4 high level group and the PF4 normal group in the malaria group.Conclusions The expression of human PF4 level has definite relationship with the plasmodium infection of Equatorial Guinea.
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OBJECTIVE: To discuss the effects of single dose of cisplatin on renal interstitial fibrosis indicators in rats dynamically. METHODS: 72 SD rats were randomly divided into normal group and cisplatin group, with 36 rats in each group. Normal group and cisplatin group were given equal volume of normal saline and cisplatin 5 mg/kg intraperitoneally on the first day, respectively. Each 6 rats were sacrificed on 8th, 14th, 30th, 50th, 60th, 90th day. The serum levels of blood urea nitrogen (BUN) and creatinine (Cr) were determined, and the degree of renal tubulointerstitial injury and relative area of renal tubulointerstitial fibrosis were evaluated. The expression of α-smooth muscle actin (α-SMA), type Ⅰ collagen (Col Ⅰ) and transforming growth factor β1 (TGF-β1) were determined in renal tissue. RESULTS: Compared with normal group, the serum levels of BUN and Cr, renal tubulointerstitial injury indexes, relative area of renal tubulointerstitial fibrosis, and the expression of α-SMA, Col Ⅰ and TGF-β1 in renal tissue were increased significantly (P<0. 05 or P<0. 01). In cisplatin group, within the 8th-90th days, serum level of BUN in rats had no significant change; serum level of Cr, renal tubulointerstitial injury indexes, renal tubulointerstitial fibrosis, the expression of a-SMA, Col Ⅰ and TGF-β1 in renal tissue increased first and then decreased. CONCLUSIONS: A single dose of clinical dose of cisplatin can induce renal interstitial fibrosis in rats, and its mechanism may be related to the expression of TGF-β1 in renal tissue.
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OBJECTIVE:To investigate the effects of Shenfukang capsules on clinical efficacy and renal function indexes of patients with renal insufficiency. METHODS:Totally 100 inpatients with renal insufficiency treated by Shenfukang cap-sules in the First Affiliated Hospital of Guangxi Medical University during Feb. to Mar. 2015 were analyzed retrospectively in respects of general information of patients,therapy plan,renal function indexs before and after treatment and clinical effica-cy. The relationship of clinical efficacy with age and duration was also analyzed. RESULTS:There were 33 cases of acute re-nal insufficiency and 67 cases of chronic renal insufficiency. The route of administration of Shenfukang capsules was oral ad-ministration(97 cases,97.00%),the main dosage was 6 capsule/d(36 cases,36.00%),and treatment duration were 0-0.05);among patients with chronic renal insufficiency,the total response rate of patients elder than 60 years old was significantly better than that of patients with ≤60 years old,with statistical significance (P<0.05). With the extension of treatment duration,the total response rate of patients with acute renal insufficiency was on the rise,and that of patients with chron-ic renal insufficiency increased first and then decreased. No obvious ADR was found during treatment. CONCLUSIONS:Shenfu-kang capsules can improve renal function in patients with renal insufficiency,and has definite curative effect on acute and chronic renal insufficiency with good security. The clinical efficacy may be related to age and treatment course.