PCK2 maintains intestinal homeostasis and prevents colitis by protecting antibody-secreting cells from oxidative stress.

Maintaining intracellular redox balance is essential for the survival, antibody secretion, and mucosal immune homeostasis of immunoglobulin A (IgA) antibody-secreting cells (ASCs). However, the relationship between mitochondrial metabolic enzymes and the redox balance in ASCs has yet to be comprehensively studied. Our study unveils the pivotal role of mitochondrial enzyme PCK2 in regulating ASCs' redox balance and intestinal homeostasis. We discover that PCK2 loss, whether globally or in B cells, exacerbates dextran sodium sulphate (DSS)-induced colitis due to increased IgA ASC cell death and diminished antibody production. Mechanistically, the absence of PCK2 diverts glutamine into the TCA cycle, leading to heightened TCA flux and excessive mitochondrial reactive oxygen species (mtROS) production. In addition, PCK2 loss reduces glutamine availability for glutathione (GSH) synthesis, resulting in a decrease of total glutathione level. The elevated mtROS and reduced GSH expose ASCs to overwhelming oxidative stress, culminating in cell apoptosis. Crucially, we found that the mitochondria-targeted antioxidant Mitoquinone (Mito-Q) can mitigate the detrimental effects of PCK2 deficiency in IgA ASCs, thereby alleviating colitis in mice. Our findings highlight PCK2 as a key player in IgA ASC survival and provide a potential new target for colitis treatment.

Spatiotemporal evolution and driving factors of ecosystem services' transformation in the Yellow River basin, China.

The Yellow River basin (YRB) holds immense ecological significance in China, but it is currently undergoing profound transformations in its ecosystem services (ESs). To formulate appropriate environmental policies, it is vital to gain a comprehensive understanding of the characteristics and influential factors driving the ESs' transformation in the YRB. The spatiotemporal dynamics in ESs was evaluated using the InVEST model, and the modes of the ESs' transformation were summarized. The elements impacting ESs' transformation and their interactions were assessed using the optimal parameter-based geographical detector (OPGD). Over the period from 1980 to 2020, the water yield within the YRB exhibited an upward trajectory, with a distinctive spatial pattern characterized by higher values in the southern and eastern regions, in contrast to lower values observed in the northern and western regions. Similarly, soil conservation demonstrated a tendency to rise over the duration of the research, with southern and western regions consistently exhibiting higher values compared to the northern and eastern regions. In contrast, habitat quality decreased over time and was accompanied by a progressive spatial decline from the southeast regions to the northwest regions. The ESs' transformation in the YRB from 1980 to 2020 indicated three modes: (1) simultaneous increases, this mode was characterized by concurrent increases in water yield and soil conservation; (2) increase and decrease, in this mode, there was an increase in soil conservation accompanied by a decrease in habitat quality; and (3) increase and deterioration, the third mode entailed an increase in water yield but a simultaneous deterioration in habitat quality. The 45-km grid was the best spatial scale for the analysis in this study. Over the span of 2000 through 2020, the ESs' transformation in the YRB was subject to the influence of natural environmental, geographic location-related, socioeconomic, and policy factors. The determinants of the spatiotemporal heterogeneity in ESs' transformation in the YRB demonstrated double-factor and nonlinear enhancement effects. The counterchange with the most significant effects on ESs' transformation were those between economic density and annual mean precipitation, annual mean temperature and ecological restoration, and the per capita income of urban residents and vegetation index.

Myxobolus xiushanensis n. sp. (Myxozoa: Myxobolidae) infecting the gill arches of Yellowhead Catfish Tachysurus fulvidraco from China.

OBJECTIVE: Myxosporidiosis of bagrid fishes has been a focus of aquaculture research in recent years. The purpose of this study is to characterize a novel myxobolid, named Myxobolus xiushanensis n. sp., infecting Yellowhead Catfish Tachysurus fulvidraco in China. METHODS: We used molecular biology, morphology, phylogeny, and histopathology in the present study. RESULT: Mature myxospores were circular to ellipsoidal in valve view, measuring 12.2 ± 0.4 µm (mean ± SD; range = 11.2-13.2 µm) in length and 10.6 ± 0.4 µm (9.5-11.1 µm) in width. Two oval polar capsules were equal in width (3.4 ± 0.2 µm; 3.0-3.8 µm) but slightly unequal in length: 5.6 ± 0.3 µm (5.3-6.1 µm) and 4.7 ± 0.2 µm (4.4-5.5 µm). The polar capsule was packed with five to seven spirals of polar tubules. Histopathological investigation demonstrated that the plasmodium under the cuticular layer of the gill arch only induced a local inflammatory response and did not cause serious damage to the gill arch's internal structure. The two small subunit (SSU) ribosomal DNA sequences of M. xiushanensis n. sp. showed 100% similarity and uniqueness, and the highest similarity with other myxosporean sequences in GenBank was 90.27% (query coverage = 94%). The secondary structures of the SSU ribosomal RNA revealed that the present species was distinctly different from related species in regions V4 and V7. Phylogenetic analysis showed that M. xiushanensis n. sp. clustered independently within a branch. CONCLUSION: These results enrich our understanding of the biodiversity of myxobolids infecting bagrid fishes and provide fundamental data for the diagnosis of myxosporidiosis.

Loss of SIRT5 promotes bile acid-induced immunosuppressive microenvironment and hepatocarcinogenesis.

BACKGROUND & AIMS: The liver is a metabolically active organ and is also 'tolerogenic', exhibiting sophisticated mechanisms of immune regulation that prevent pathogen attacks and tumorigenesis. How metabolism impacts the tumor microenvironment (TME) in hepatocellular carcinoma (HCC) remains understudied. METHODS: We investigated the role of the metabolic regulator SIRT5 in HCC development by conducting metabolomic analysis, gene expression profiling, flow cytometry and immunohistochemistry analyses in oncogene-induced HCC mouse models and human HCC samples. RESULTS: We show that SIRT5 is downregulated in human primary HCC samples and that Sirt5 deficiency in mice synergizes with oncogenes to increase bile acid (BA) production, via hypersuccinylation and increased BA biosynthesis in the peroxisomes of hepatocytes. BAs act as a signaling mediator to stimulate their nuclear receptor and promote M2-like macrophage polarization, creating an immunosuppressive TME that favors tumor-initiating cells (TICs). Accordingly, high serum levels of taurocholic acid correlate with low SIRT5 expression and increased M2-like tumor-associated macrophages (TAMs) in HCC patient samples. Finally, administration of cholestyramine, a BA sequestrant and FDA-approved medication for hyperlipemia, reverses the effect of Sirt5 deficiency in promoting M2-like polarized TAMs and liver tumor growth. CONCLUSIONS: This study uncovers a novel function of SIRT5 in orchestrating BA metabolism to prevent tumor immune evasion and suppress HCC development. Our results also suggest a potential strategy of using clinically proven BA sequestrants for the treatment of patients with HCC, especially those with decreased SIRT5 and abnormally high BAs. LAY SUMMARY: Hepatocellular caricinoma (HCC) development is closely linked to metabolic dysregulation and an altered tumor microenvironment. Herein, we show that loss of the metabolic regulator Sirt5 promotes hepatocarcinogenesis, which is associated with abnormally elevated bile acids and subsequently an immunosuppressive microenvironment that favors HCC development. Targeting this mechanism could be a promising clinical strategy for HCC.

Comparison between 1,2-Dihydropyridine and 1,4-Dihydropyridine on Hydride-Donating Ability and Activity.

In this paper, detailed comparisons of the driving force in thermodynamics and intrinsic force in the kinetics of 1,2-dihydropyridine and 1,4-dihydropyridine isomers of PNAH, HEH, and PYH in hydride transfer reactions are made. For 1,2-PNAH and 1,4-PNAH, the values of the thermodynamic driving forces, kinetic intrinsic barriers, and thermo-kinetic parameters are 60.50 and 61.90 kcal/mol, 27.92 and 26.34 kcal/mol, and 44.21 and 44.12 kcal/mol, respectively. For 1,2-HEH and 1,4-HEH, the values of the thermodynamic driving forces, kinetic intrinsic barriers, and thermo-kinetic parameters are 63.40 and 65.00 kcal/mol, 31.68 and 34.96 kcal/mol, and 47.54 and 49.98 kcal/mol, respectively. For 1,2-PYH and 1,4-PYH, the order of thermodynamic driving forces, kinetic intrinsic barriers, and thermo-kinetic parameters are 69.90 and 72.60 kcal/mol, 33.06 and 25.74 kcal/mol, and 51.48 and 49.17 kcal/mol, respectively. It is not difficult to find that thermodynamically favorable structures are not necessarily kinetically favorable. In addition, according to the analysis of thermo-kinetic parameters, 1,4-PNAH, 1,2-HEH, and 1,4-PYH have a strong hydride-donating ability in actual chemical reactions.

Comparison of the Hydride-Donating Ability and Activity of Five- and Six-Membered Benzoheterocyclic Compounds in Acetonitrile.

In this work, we compared the hydride-donating ability of five-membered benzoheterocyclic compounds (FMB) and six-membered benzoheterocyclic compounds (SMB), isomers of DMBI and DMIZ and of DMPZ and DMPX, using detailed thermodynamic driving forces [ΔGo (XH)], kinetic intrinsic barriers (ΔG≠XH/X), and thermo-kinetic parameters [ΔG≠° (XH)]. For DMBI and DMIZ, the values of ΔGo (XH), ΔG≠XH/X, and ΔG≠° (XH) are 49.2 and 53.7 kcal/mol, 35.88 and 42.04 kcal/mol, and 42.54 and 47.87 kcal/mol, respectively. For DMPZ and DMPX, the values of ΔGo (XH), ΔG≠XH/X, and ΔG≠° (XH) are 73.2 and 79.5 kcal/mol, 35.34 and 25.02 kcal/mol, and 54.27 and 52.26 kcal/mol, respectively. It is easy to see that the FMB isomers are thermodynamically dominant and that the SMB isomers are kinetically dominant. Moreover, according to the analysis of ΔG≠° (XH), compared to the SMB isomers, the FMB isomers have a stronger hydride-donating ability in actual chemical reactions.

Molecular identification of an immunity- and Ferroptosis-related gene signature in non-small cell lung Cancer.

BACKGROUND: Lung cancer is one of the dominant causes of cancer-related deaths worldwide. Ferroptosis, an iron-dependent form of programmed cell death, plays a key role in cancer immunotherapy. However, the role of immunity- and ferroptosis-related gene signatures in non-small cell lung cancer (NSCLC) remain unclear. METHODS: RNA-seq data and clinical information pertaining to NSCLC were collected from The Cancer Genome Atlas dataset. Univariate and multivariate Cox regression analyses were performed to identify ferroptosis-related genes. A receiver operating characteristic (ROC) model was established for sensitivity and specificity evaluation. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the function roles of differentially expressed genes. RESULTS: A signature composed of five ferroptosis-related genes was established to stratify patients into high- and low-risk subgroups. In comparison with patients in the low-risk group, those in the high-risk one showed significantly poor overall survival in the training and validation cohorts (P < 0.05). Multivariate Cox regression analysis indicated risk score to be an independent predictor of overall survival (P < 0.01). Further, the 1-, 2-, and 3-year ROCs were 0.623 vs. 0.792 vs. 0.635, 0.644 vs. 0.792 vs. 0.634, and 0.631 vs. 0.641 vs. 0.666 in one training and two validation cohorts, respectively. Functional analysis revealed that immune-related pathways were enriched and associated with abnormal activation of immune cells. CONCLUSIONS: We identified five immunity- and ferroptosis-related genes that may be involved in NSCLC progression and prognosis. Targeting ferroptosis-related genes seems to be an alternative to clinical therapy for NSCLC.

SIRT5 inhibits peroxisomal ACOX1 to prevent oxidative damage and is downregulated in liver cancer.

Peroxisomes account for ~35% of total H2O2 generation in mammalian tissues. Peroxisomal ACOX1 (acyl-CoA oxidase 1) is the first and rate-limiting enzyme in fatty acid ß-oxidation and a major producer of H2O2 ACOX1 dysfunction is linked to peroxisomal disorders and hepatocarcinogenesis. Here, we show that the deacetylase sirtuin 5 (SIRT5) is present in peroxisomes and that ACOX1 is a physiological substrate of SIRT5. Mechanistically, SIRT5-mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation in both cultured cells and mouse livers. Deletion of SIRT5 increases H2O2 production and oxidative DNA damage, which can be alleviated by ACOX1 knockdown. We show that SIRT5 downregulation is associated with increased succinylation and activity of ACOX1 and oxidative DNA damage response in hepatocellular carcinoma (HCC). Our study reveals a novel role of SIRT5 in inhibiting peroxisome-induced oxidative stress, in liver protection, and in suppressing HCC development.

Rapid diagnosis of IDH1-mutated gliomas by 2-HG detection with gas chromatography mass spectrometry.

The metabolic genes encoding isocitrate dehydrogenase (IDH1, 2) are frequently mutated in gliomas. Mutation of IDH defines a distinct subtype of glioma and predicts therapeutic response. IDH mutation has a remarkable neomorphic activity of converting α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG), which is now commonly referred to as an oncometabolite and biomarker for gliomas. PCR-sequencing (n = 220), immunohistochemistry staining (IHC, n = 220), and gas chromatography mass spectrometry (GC-MS, n = 87) were applied to identify IDH mutation in gliomas, and the sensitivity and specificity of these strategies were compared. PCR-sequencing and IHC staining are reliable for retrospective assessment of IDH1 mutation in gliomas, but both methods usually take 1-2 days, which hinders their application for rapid diagnosis. GC-MS-based methods can detect 2-HG qualitatively and quantitatively, offering information on the IDH1 mutation status in gliomas with the sensitivity and specificity being 100%. Further optimization of the GC-MS based methodology (so called as the mini-column method) enabled us to determine 2-HG within 40 min in glioma samples without complex or time-consuming preparation. Most importantly, the ratio of 2-HG/glutamic acid was shown to be a reliable parameter for determination of mutation status. The mini-column method enables rapid identification of 2-HG, providing a promising strategy for intraoperative diagnosis of IDH1-mutated gliomas in the future.

Photoconductive generation and detection of THz-bandwidth pulses using near-field coupling to a free-space metallic slit waveguide.

THz-bandwidth pulses are generated, transmitted along a gold-plated stainless steel metallic slit waveguide, and detected with 1.5 THz bandwidth and 60 dB dynamic range. The source and detector were edge-pumped slotlines on LT-GaAs placed within the near-field region of the waveguide entrance and exit aperture. The motivation for this work was to develop a complete dispersion-free THz system which was simple to manufacture and could be utilized for free-space waveguide experimentation.

THz-TDS using a photoconductive free-space linear tapered slot antenna transmitter.

A near-field edge-coupled photoconductive free-space linear tapered slot antenna has been constructed as a planar alternative to the standard photoconductive switch coupled to a silicon substrate lens. The temporal response along the optical axis is investigated to ensure the structure itself does not introduce pulse distortion which would fundamentally limit the usefulness of the structure. Experimental results show that a 1.6 THz bandwidth with a ≈50dB dynamic range is achievable with the new structure which is comparable to our reference experiment with a standard silicon substrate lens. The investigated structure has the added benefit of a potential substantial physical size reduction and can also be used to excite waveguides in the near-field.

Extraction of Lactobacillus acidophilus CICC 6074 S-Layer Proteins and Their Ability to Inhibit Enteropathogenic Escherichia coli.

An adhesion-related protein of Lactobacillus acidophilus strain CICC 6074 involved in binding to Caco-2 cells and inhibiting Enteropathogenic Escherichia coli (EPEC) was isolated and characterized. The S-layer protein was extracted with 5M LiCl and the active fraction purified by gel filtration (G-75). The S-layer protein was visualized by SDS-PAGE and characterized by estimating the relative molecular weight using mass spectra. The inhibitory effect of L. acidophilus and its S-layer proteins on the ability of EPEC to adhere to cells was explored by using a Caco-2 cell model. The results suggest that the S-layer proteins of L. acidophilus are adhesive in nature and are involved in the competitive exclusion of EPEC from Caco-2 cells.

Plasmon-Enhanced below Bandgap Photoconductive Terahertz Generation and Detection.

We use plasmon enhancement to achieve terahertz (THz) photoconductive switches that combine the benefits of low-temperature grown GaAs with mature 1.5 µm femtosecond lasers operating below the bandgap. These below bandgap plasmon-enhanced photoconductive receivers and sources significantly outperform commercial devices based on InGaAs, both in terms of bandwidth and power, even though they operate well below saturation. This paves the way for high-performance low-cost portable systems to enable emerging THz applications in spectroscopy, security, medical imaging, and communication.

Vitamin D deficiency and the risk of anemia: a meta-analysis of observational studies.

AIMS: Anemia and vitamin D deficiency (VDD) are both very important health issues, recent accumulating evidence shows that VDD is prevalent in individuals with anemia. This meta-analysis aimed to detect a relationship between VDD and anemia. METHODS: We identified eligible studies by searching the Pub Med, Embase and Cochrane Library before October 2014. Quality assessments were performed with the Newcastle-Ottawa Scale. Heterogeneity was evaluated by Cochran's Q test and source of heterogeneity was detected by subgroup analysis and sensitivity analysis. RESULTS: A total of seven studies involving 5183 participants were included in the meta-analysis. VDD was associated with an increased incidence of anemia (OR = 2.25, 95% CI = 1.47-3.44), with significant evidence of heterogeneity among these studies (p for heterogeneity < 0.001, I(2) = 84.0%). The subgroup and sensitivity analysis confirmed the stability of the results and no publication bias was detected. CONCLUSION: Our outcomes showed that VDD increased the risk of developing anemia. More researches are warranted to clarify an understanding of the association between VDD and risk of anemia.

Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS.

Mitochondria manganese superoxide dismutase (SOD2) is an important antioxidant enzyme, deficiency of which is associated with various human diseases. The known primary regulation of SOD2 is through transcriptional activation. Here, we report that SOD2 is acetylated at Lys 68 and that this acetylation decreases SOD2 activity. Mitochondrial deacetylase SIRT3 binds to, deacetylates and activates SOD2. Increase of reactive oxygen species (ROS) levels stimulates SIRT3 transcription, leading to SOD2 deacetylation and activation. SOD2-mediated ROS reduction is synergistically increased by SIRT3 co-expression, but is cancelled by SIRT3 depletion. These results reveal a new post-translational regulation of SOD2 by means of acetylation and SIRT3-dependent deacetylation in response to oxidative stress.

The description of Myxobolus meijiangensis n. sp. (Myxozoa: Myxobolidae) and its pathogenicity to the gills of goldfish.

Myxobolus Bütschli, 1882 is the most speciose myxozoan genus, although some species have only been described according to the morphological characteristics of spores. In the present study, a new Myxobolus species infecting the gill lamellae of goldfish from Chongqing, China, was described using a comprehensive analysis of morphological, molecular, and histological data. Mature spores were flat-pear in valvular view with tapering anterior and rounded posterior ends, measuring 11.0 ± 0.4 (10.4-11.6) µm in length and 10.3 ± 0.3 (9.6-11.0) µm in width. Two equal-sized elongate pyriform polar capsules were 5.6 ± 0.6 (4.5-6.4) µm long and 3.5 ± 0.5 (2.4-4.1) µm wide. Polar tubules were coiled with 8 or 9 turns. The small-subunit ribosomal DNA gene sequence length of the present species was 1951 nt, and the highest similarity was 97.99% with M. pyramidis. Comparative analysis of the morphological and molecular data revealed that the present species was distinct from other known myxosporeans. Plasmodia were located at the interlamellar troughs nearing the top of the primary gills. Infection by the present species destroyed the original structure of gill lamellae and caused an inflammatory response, eventually leading to fish dyspnea. The morphological, molecular, and pathological data from the present study can be used for aquaculture since they provide guidance for easy detection and future control of this myxosporidiosis.

Montelukast Inhibits Lung Cancer Cell Migration by Suppressing Cysteinyl Leukotriene Receptor 1 Expression In vitro.

BACKGROUND: Lung cancer is a major threat to public health and remains difficult to treat. Repositioning of existing drugs has emerged as a therapeutic strategy in lung cancer. Clinically, low-dose montelukast has been used to treat asthma. OBJECTIVE: We evaluated the potential of using montelukast to treat lung cancer. METHODS: Migration was detected using wound-healing and Transwell assays, the expression of CysLT1 using western blotting, and subcellular localization of CysLT1 using immunofluorescence. CRISPR/Cas9 technology was used to further investigate the function of CysLT1. RESULTS: Subcellular localization staining showed that the CysLT1 distribution varied in murine and human lung cancer cell lines. Furthermore, montelukast suppressed CysLT1 expression in lung cancer cells. The treated cells also showed weaker migration ability compared with control cells. Knockout of CysLT1 using CRISPR/Cas9 editing in A549 cells further impaired the cell migration ability. CONCLUSION: Montelukast inhibits the migration of lung cancer cells by suppressing CysLT1 expression, demonstrating the potential of using CysLT1 as a therapeutic target in lung cancer.

Characteristic Activity Parameters of Electron Donors and Electron Acceptors.

It is well-known that for an electron transfer reaction, the electron-donating ability of electron donors and the electron-accepting ability of electron acceptors can be quantitatively described by the oxidation potential of electron donors and the reduction potential of electron acceptors. However, for an electron transfer reaction, the electron-donating activity of electron donors and the electron-accepting activity of electron acceptors cannot be quantitatively described by a characteristic parameter of electron donors and a characteristic parameter of electron acceptors till now. In this paper, a characteristic activity parameter of electron donors and electron acceptors named as their thermo-kinetic parameter is proposed to quantify the electron-donating activity of electron donors and the electron-accepting activity of electron acceptors in electron transfer reactions. At the same time, the thermo-kinetic parameter values of 70 well-known electron donors and the corresponding 70 conjugated electron acceptors in acetonitrile at 298 K are determined. The activation free energies of 4900 typical electron transfer reactions in acetonitrile at 298 K are estimated according to the thermo-kinetic parameter values of 70 electron donors and 70 conjugated electron acceptors, and the estimated results have received good verification of the corresponding independent experimental measurements. The physical meaning of the thermo-kinetic parameter is examined. The relationship of the thermo-kinetic parameter with the corresponding redox potential as well as the relationship of the activation free energy with the corresponding thermodynamic driving force of electron transfer reactions is examined. The results show that the observed relationships between the thermo-kinetic parameters and the redox potentials as well as the observed relationships between the activation free energy and the thermodynamic driving force depend on the choice of electron donors and electron acceptors as well as the electron transfer reactions. The greatest contribution of this paper is to realize the symmetry and unification of kinetic equations and the corresponding thermodynamic equations of electron transfer reactions.

The dynamic patterns and driving factors of land use conflict in the Yellow River basin of China.

Land use conflict, as the spatial manifestation of conflicting human-land relationship, has a profound impact on sustainable use of regional land resources. Taking the Yellow River Basin (YRB) as an example, a land use conflict assessment model was constructed based on landscape pattern indices. The dynamic patterns and driving factors of land use conflict in the YRB and the corresponding driving factors were then assessed from 2000 to 2020 based on spatial autocorrelation analysis and the geodetector method. Significant spatial and temporal differences in land use conflict were observed in the YRB from 2000 to 2020. During this period, the area of stable controllable decreased by 3465 km2, whereas the areas of strong and extreme conflict increased by 34,964 and 13,057 km2, respectively. The expansion of areas with extreme and strong conflict mostly occurred in regions with high urbanization and human activity, including northern Shaanxi, Hetao Plain, and the Yellow River Delta. The distribution of land use conflict in the YRB from 2000 to 2020 was characterized by significant spatial agglomeration; high-value cluster conflict mainly extended from the midstream area to the upstream area, whereas low-value clusters tended to be concentrated in the upstream area of the Qinghai and Qilian Mountains. The spatial and temporal differentiation in land use conflict from 2000 to 2020 was influenced by factors related to the natural environment, geographic location, social economy, and regional policy in the YRB. The effects of elevation, distance to the nearest major river, population, economic density, and per capita disposable income of residents increased continuously during the study period, whereas the influences of mean annual precipitation and ecological retreat weakened. Analysis of the interactions between driving factors showed significant dual-factor and non-liner enhancement effects on the spatial and temporal differentiation in land use conflict. The findings provide a scientific reference for the comprehensive management of national land and ecological construction in the YRB.

Comparison of the second-line treatments for patients with small cell lung cancer sensitive to previous platinum-based chemotherapy: A systematic review and Bayesian network analysis.

Objective: It remains unclear what the best second-line treatment is for patients with small-cell lung cancer sensitive to previous platinum-based chemotherapy. Methods: We systematically screened randomized controlled trials from several online databases. The primary outcome was objective response rate (ORR), and the secondary outcomes were disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and hematological complications graded 3 to 5. The efficacy of included treatments was ranked by surface under the cumulative ranking curve (SUCRA) value. Results: We included eleven trials involving 1560 patients in quantitative analysis. Triple chemotherapy containing platinum (TP, combination of cisplatin, etoposide, and irinotecan) was associated with favorable ORR (intravenous topotecan vs TP; odds ratio: 0.13, 95% CI:0.03-0.63; SUCRA, 0.94) and PFS (vs intravenous topotecan; hazard ratio, 0.5; 95% CI: 0.25-0.99; SUCRA, 0.90). Belotecan ranked highest for OS (SUCRA, 0.90), while intravenous topotecan plus Ziv-aflibercept ranked highest for DCR (SUCRA, 0.75). TP was more likely to cause anemia and thrombocytopenia while intravenous topotecan plus Ziv-aflibercept resulted in most neutrocytopenia. Conclusion: TP is the first recommendation for the second-line treatment of sensitive relapsed SCLC. TP achieved priority in ORR and PFS with the most frequent adverse effects in anemia and thrombocytopenia. For patients who cannot tolerate the hematological adverse effects of triple chemotherapy, amrubicin is an optional option. Amrubicin had relatively good ORR and PFS, accompanied by fewer hematological complications. The rechallenge of the platinum doublet is inferior to amrubicin in ORR, DCR, and PFS. Oral topotecan has a similar effect compared with IV topotecan, but oral topotecan was associated with slightly higher safety and less stress in nursing. Belotecan contributed to the best PFS with slightly better safety but was not ideal in other outcomes. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022358256.