Recombinant mannan-binding lectin magnetic beads increase pathogen detection in immunocompromised patients.

The microbiological diagnosis of infection for hematological malignancy patients receiving chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients relies primarily on standard microbial culture, especially blood culture, which has many shortcomings, such as having low positive rates, being time-consuming and having a limited pathogenic spectrum. In this prospective observational self-controlled test accuracy study, blood, cerebrospinal fluid (CSF), and bronchoalveolar lavage fluid (BALF) samples were collected from chemotherapy or allo-HSCT patients with clinical symptoms of infections who were hospitalized at Peking University First Hospital. Possible pathogens were detected by the method based on recombinant mannan-binding lectin (MBL) magnetic bead enrichment (M1 method) and simultaneously by a standard method. The analytical sensitivity of M1 method was close to that of standard culture method. Besides, the turn-around time of M1-method was significantly shorter than that of standard culture method. Moreover, the M1 method also added diagnostic value through the detection of some clinically relevant microbes missed by the standard method. M1 method could significantly increase the detection efficiency of pathogens (including bacteria and fungi) in immunocompromised patients. KEY POINTS: • The detection results of M1-method had a high coincidence rate with that of standard method • M1 method detected many pathogens which had not been found by standard clinic method.

Analysis of the Impact of Ambulatory Care Based on Social Support on the Quality of Life of Patients with Graves' Ophthalmopathy.

Background: Graves' ophthalmopathy (GO) is an organ-specific autoimmune disease and is a common orbital condition that can possibly lead to blindness. Objective: Our aim was to find out how patients with GO are affected in terms of quality of life (QoL) by traditional nursing care and social support mobile care. Methods: A total of 38 patients with GO who were admitted to Beijing Chao-Yang Hospital in China between December 2018 and December 2023 underwent life evaluations before treatment, 6 weeks after treatment and 6 months after treatment. The control group comprised 27 patients and the experimental group comprised 11 patients. They were then split into 2 groups based on the European Group on Graves' Orbitopathy (EUGOGO) improvement criteria: improved and unimproved. Then, the mean value of the Graves' Ophthalmopathy-Quality of Life Inventory (GO-QOL) alterations were compared to see if there was any difference, and their post-treatment QoL was examined. Results: (1) Patients who improved in this study had a mean change in visual energy scale scores before and after treatment that was higher than the patients who did not (13.39 vs 0.00, respectively); (2) The social functioning scores on the GO-QOL scale increased by 17.05 points in the control group before and after treatment (P < .01); (3) A total of 15.4% of patients had a GO-QOL score >90 after therapy, indicating a significant impact on their lives. In the experimental group, scores on the visual power energy scale improved by 16.27 points after treatment compared with before treatment (P = .028). Conclusion: When used in conjunction with traditional treatment, social supportive mobile care improves the outcomes in patients with GO and is superior to traditional care on its own.

The research of river basin ecological compensation based on water emissions trading mechanism.

By integrating the successful case of the European Union emissions trading system, this study proposes a water emissions trading system, a novel method of reducing water pollution. Assuming that upstream governments allocate initial quotas to upstream businesses as the compensation standard, this approach defines the foundational principles of market trading mechanisms and establishes a robust watershed ecological compensation model to address challenges in water pollution prevention. To be specific, the government establishes a reasonable initial quota for upstream enterprises, which can be used to limit the emissions of upstream pollution. When enterprises exceed their allocated emissions quota, they face financial penalties. Conversely, these emissions rights can be transformed into profitable assets by participating in the trading market as a form of ecological compensation. Numerical simulations demonstrate that various pollutant emissions from upstream businesses will have various effects on the profits of other businesses. Businesses in the upstream region received reimbursement from the assigned emission rights through the market mechanism, demonstrating that ecological compensation for the watershed can be achieved through the market mechanism. This novel market trading system aims at controlling emissions management from the perspectives of individual enterprises and ultimately optimizing the aquatic environment.

Metal-Organic Framework Supported Low-Nuclearity Cluster Catalysts for Highly Selective Carbon Dioxide Electroreduction to Ethanol.

It is still a great challenge to achieve high selectivity of ethanol in CO2 electroreduction reactions (CO2RR) because of the similar reduction potentials and lower energy barrier of possible other C2+ products. Here, we report a MOF-based supported low-nuclearity cluster catalysts (LNCCs), synthesized by electrochemical reduction of three-dimensional (3D) microporous Cu-based MOF, that achieves a single-product Faradaic efficiency (FE) of 82.5% at -1.0 V (versus the reversible hydrogen electrode) corresponding to the effective current density is 8.66 mA cm-2. By investigating the relationship between the species of reduction products and the types of catalytic sites, it is confirmed that the multi-site synergism of Cu LNCCs can increase the C-C coupling effect, and thus achieve high FE of CO2-to-ethanol. In addition, density functional theory (DFT) calculation and operando attenuated total reflectance surface-enhanced infrared absorption spectroscopy further confirmed the reaction path and mechanism of CO2-to-EtOH.

Mapping of major QTL and candidate gene analysis for hull colour in foxtail millet (Setaria italica (L.) P. Beauv.).

BACKGROUND: Hull colour is an important morphological marker for selection in seed production of foxtail millet. However, the molecular mechanisms underlying hull colour variation remain unknown. RESULTS: An F7 recombinant inbred line (RIL) population containing 215 lines derived from Hongjiugu × Yugu18 was used to analyze inheritance and detect the quantitative trait loci (QTL) for four hull colour traits using major gene plus polygene mixed inheritance analysis and composite interval mapping (CIM) in four environments. Genetic analysis revealed that the hull colour L* value (HCL*) was controlled by two major genes plus additive polygenes, the hull colour a* value (HCa*) was controlled by three major genes, the hull colour b* value (HCb*) was controlled by two major genes plus polygenes, and the hull colour C* value (HCC*) was controlled by four major genes. A high-density genetic linkage map covering 1227.383 cM of the foxtail millet genome, with an average interval of 0.879 cM between adjacent bin markers, was constructed using 1420 bin markers. Based on the genetic linkage map and the phenotypic data, a total of 39 QTL were detected for these four hull colour traits across four environments, each explaining 1.50%-49.20% of the phenotypic variation. Of these, six environmentally stable major QTL were co-localized to regions on chromosomes 1 and 9, playing a major role in hull colour. There were 556 annotated genes within the two QTL regions. Based on the functions of homologous genes in Arabidopsis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) gene annotations, five genes were predicted as candidate genes for further studies. CONCLUSIONS: This is the first study to use an inheritance model and QTL mapping to determine the genetic mechanisms of hull colour trait in foxtail millet. We identified six major environmentally stable QTL and predicted five potential candidate genes to be associated with hull colour. These results advance the current understanding of the genetic mechanisms underlying hull colour traits in foxtail millet and provide additional resources for application in genomics-assisted breeding and potential isolation and functional characterization of the candidate genes.

Single-cell sequencing reveals the immune microenvironment landscape related to anti-PD-1 resistance in metastatic colorectal cancer with high microsatellite instability.

BACKGROUND: The objective response rate of microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) patients with first-line anti-programmed cell death protein-1 (PD-1) monotherapy is only 40-45%. Single-cell RNA sequencing (scRNA-seq) enables unbiased analysis of the full variety of cells comprising the tumor microenvironment. Thus, we used scRNA-seq to assess differences among microenvironment components between therapy-resistant and therapy-sensitive groups in MSI-H/mismatch repair-deficient (dMMR) mCRC. Resistance-related cell types and genes identified by this analysis were subsequently verified in clinical samples and mouse models to further reveal the molecular mechanism of anti-PD-1 resistance in MSI-H or dMMR mCRC. METHODS: The response of primary and metastatic lesions to first-line anti-PD-1 monotherapy was evaluated by radiology. Cells from primary lesions of patients with MSI-H/dMMR mCRC were analyzed using scRNA-seq. To identify the marker genes in each cluster, distinct cell clusters were identified and subjected to subcluster analysis. Then, a protein‒protein interaction network was constructed to identify key genes. Immunohistochemistry and immunofluorescence were applied to verify key genes and cell marker molecules in clinical samples. Immunohistochemistry, quantitative real-time PCR, and western blotting were performed to examine the expression of IL-1ß and MMP9. Moreover, quantitative analysis and sorting of myeloid-derived suppressor cells (MDSCs) and CD8+ T cells were performed using flow cytometry. RESULTS: Tumor responses in 23 patients with MSI-H/dMMR mCRC were evaluated by radiology. The objective response rate was 43.48%, and the disease control rate was 69.57%. ScRNA-seq analysis showed that, compared with the treatment-resistant group, the treatment-sensitive group accumulated more CD8+ T cells. Experiments with both clinical samples and mice indicated that infiltration of IL-1ß-driven MDSCs and inactivation of CD8+ T cells contribute to anti-PD-1 resistance in MSI-H/dMMR CRC. CONCLUSIONS: CD8+ T cells and IL-1ß were identified as the cell type and gene, respectively, with the highest correlation with anti-PD-1 resistance. Infiltration of IL-1ß-driven MDSCs was a significant factor in anti-PD-1 resistance in CRC. IL-1ß antagonists are expected to be developed as a new treatment for anti-PD-1 inhibitor resistance.

Effect of Halide Anions on the Electroreduction of CO2 to C2 H4 : A Density Functional Theory Study.

The halide anions present in the electrolyte improve the Faradaic efficiencies (FEs) of the multi-hydrocarbon (C2+ ) products for the electrochemical reduction of CO2 over copper (Cu) catalysts. However, the mechanism behind the increased yield of C2+ products with the addition of halide anions remains indistinct. In this study, we analysed the mechanism by investigating the electronic structures and computing the relative free energies of intermediates formed from CO2 to C2 H4 on the Cu (100) facet based on density functional theory (DFT) calculations. The results show that formyl *CHO from the hydrogenation reaction of the adsorbed *CO acts as the key intermediate, and the C-C coupling reaction occurs preferentially between *CHO and *CO with the formation of a *CHO-CO intermediate. We then propose a free-energy pathway of C2 H4 formation. We find that the presence of halide anions significantly decreases the free energy of the *CHOCH intermediate, and enhances desorption of C2 H4 in the order of I- >Cl- >Br- >F- . Lastly, the obtained results are rationalized through Bader charge analysis.

A nitroreductase-MOF biocatalyst for the degradation of nitroaromatic contaminants and fluorescent labeling of carbohydrates.

NfsB (nitroreductase fromEscherichia coli) can catalyze nitroaromatic compounds to aromatic amines under mild conditions. Compared with the purified enzyme NfsB, we found that the crude enzyme demonstrated better thermal stability and tolerance against a wide pH range, rendering it convenient to use and cost-effective as it did not require any downstream processing. In addition, we introduced metal-organic frameworks to immobilize the crude-NfsB. The resulting composite, crude-NfsB@ZIF-90, showed excellent catalytic performance and reusability, and it also demonstrated good catalytic activity in organic solvents, rendering it more efficient for the removal of nitroaromatic contaminants in complex environments. The nitroreductase-ZIF-90 biocatalyst can be used for fluorescent labeling of carbohydrates, which is favorable for the study of the function of carbohydrates.

Efficacy and safety of antibiotic therapy for post-Lyme disease? A systematic review and network meta-analysis.

BACKGROUND: At present, the pathogenesis of post-treatment Lyme disease (PTLDS) is not clear, so the treatment scheme of PTLDS, especially antibiotic treatment, is still controversial. This study aims to evaluate the efficacy of antibiotics in the treatment of PTLDS using network meta-analysis (NMA). METHODS: Following PRISMA guidelines, a systematic literature search was conducted on randomized controlled trials in PubMed, EMBASE, Web of Science and Cochrane Library (the literature was published from database inception through December 16, 2022). Using random effect model and fixed effect model. STATA17.0 software was used to evaluate the quality and heterogeneity of the included research literature. RESULTS: The system included 4 randomized controlled trials (485 subjects). The network meta-analysis showed that ceftriaxone had better results than placebo [Mean = 0.87, 95% CI (0.02, 1.71)] and doxycycline [Mean = 1.01, 95% CI (0.03, 1.98)] in FSS scale scores. There was no statistical difference in FSS scale scores of other drugs after treatment. In terms of FSS score results, Ceftriaxone was the best intervention according to the SUCRA value of each treatment (97.7). The analysis of outcome indicators such as Beck Depression Inventory (BDI), Mental-health Scale and Physical-functioning scale showed that there was no statistically significant difference between the antibiotic group and placebo group. CONCLUSION: Ceftriaxone treatment may be the best choice for antibiotic treatment of PTLD, which provides useful guidance for antibiotic treatment of PTLD in the future.

Periodontal ligament-associated protein-1 engages in teeth overeruption and periodontal fiber disorder following occlusal hypofunction.

BACKGROUND AND OBJECTIVE: Teeth overeruption is a problem of clinical significance, but the underlying mechanism how changes in external occlusal force convert to the periodontium remodeling signals has been a largely under explored domain. And recently, periodontal ligament-associated protein-1 (PLAP-1)/asporin was found to play a pivotal role in maintaining periodontal homeostasis. The aim of this study was to explore the function of PLAP-1 in the periodontally hypofunctional tissue turnover. METHODS: After extracting left maxillary molars in mice, the left and right mandibular molars were distributed into hypofunction group (HG) and control group (CG), respectively. Mice were sacrificed for radiographic, histological, and molecular biological analyses after 1, 4 and 12 weeks. In vitro, dynamic compression was applied using Flexcell FX-5000 Compression System to simulate intermittent occlusal force. The expression of PLAP1 in loaded and unloaded human periodontal ligament cells (hPDLCs) was compared, and its molecular biological effects were further explored by small interfering RNA (siRNA) targeting PLAP1. RESULTS: In vivo, fiber disorder in periodontal ligament (PDL), bone apposition at furcation regions, and bone resorption in alveolar bone were illustrated in the HG compared with the CG. In addition, PLAP-1 positive area decreased significantly in PDL following occlusal unloading. In vitro, the loss of compressive loading relatively downregulated PLAP1 expression, which was essential to promote collagen I but inhibit osterix and osteocalcin expression in hPDLCs. CONCLUSIONS: PLAP-1 presumably plays a pivotal role in occlusal force-regulated periodontal homeostasis by facilitating collagen fiber synthesis in hPDLCs and suppressing excessive osteoblast differentiation, further preventing teeth from overeruption. Further evidence in PLAP-1 conditional knockout mice is needed.

Exploring electronic energy level structure and excited electronic states of ß-carotene using DFT.

Carotenoids are a class of natural pigments that play a fundamental role in photosynthesis and optoelectronics. However, the complexity of their energy level structure and electronic states has prevented a clear interpretation of their photophysics and photochemistry. The mediating nonradiative decay of the bright S2 state to the dark S1 state of carotenoids involves a population of bridging intermediate state. Herein, time-dependent DFT was used to study the energy level and electronic excitation process of ß-carotene. A π-π* transition and π electron delocalization of electron excitation could be inferred based on the difference in the electron cloud distribution of the HOMO and LUMO orbitals. Through the electronic transition contribution in the UV-vis spectra and the electron density difference between the ground state and the excited state, the electronic energy level structure and possible dark state were analyzed. On this basis, the electronic excitation process of ß-carotene was theoretically studied by combining electron-hole analysis and transition density matrix (TDM). There was a charge transfer from the ß-ionone ring to the long-chain in the (S0) → (S2), (S0) → (S4) and (S0) → (S5).

Intermolecular energy transfer-enhanced super-broadband stimulated Raman scattering in cyclohexane-benzene mixtures.

Supercontinuum radiation has found numerous applications in diverse fields encompassing spectroscopy, pulse compression, and tunable laser sources. Anomalous enhanced stimulated Raman scattering (SRS) of cyclohexane-benzene mixtures was obtained in this study. SRS of the pure solvent, the multi-order Stokes of the strongest fundamental vibration modes, and energy transfer in intra-molecular modes were observed. SRS of the mixture revealed that the cross-pumping effect was generated between the C-H stretching (v2) mode of cyclohexane and the C=C ring skeleton (v1) mode of benzene, thereby producing the intermolecular secondary stimulated Raman emission and the appearance of two super-broadband radiations at 664.36-673.9 nm and 704.62-729.22 nm. The results suggest that the energy transfer of intermolecular vibrational modes, where the strongest vibrational mode excites other vibrational modes, is a simple approach for generating supercontinuum coherent radiation.

The effectiveness of self-management programme based on multilevel social resources utilization in diabetes mellitus patients: A randomized controlled study.

AIMS: This study aimed to test the effects of a novel diabetes self-management education (DSME) programme focused on multilevel social resources utilization on improving self-management behaviour, social resources utilization and haemoglobin Alc (HbA1c ) in patients with type 2 diabetes mellitus (T2DM). METHODS: A randomized controlled design was used. A total of 118 participants with T2DM from two communities were recruited through randomized sampling, and randomly assigned to the novel DSME group or the traditional DSME group. DSME focusing on multilevel social resources utilization was implemented in the novel DSME group. Data were collected at baseline (T0 ), at the end of the intervention (T1 ) and 3 months after the end of intervention (T2 ) from 3 March to 16 November 2014. RESULTS: Comparing these two groups, the participants in the novel DSME group reported significantly better improvement in self-management behaviour and social resources utilization at T1 and T2 (all p < 0.01). A significant difference was found in the mean improvement of HbA1c level between the two groups at T2 (p < 0.05). CONCLUSIONS: The novel DSME programme focused on multilevel social resources utilization can effectively enhance T2DM patients' self-management behaviour and social resource utilization and lower HbA1c levels. More importantly, the effects could last longer.

XGBoost-aided prediction of lip prominence based on hard-tissue measurements and demographic characteristics in an Asian population.

INTRODUCTION: Prediction of lip prominence based on hard-tissue measurements could be helpful in orthodontic treatment planning and has been challenging and formidable thus far. METHODS: A machine learning-based cross-sectional study was conducted on 1549 patients. Hard-tissue measurements and demographic information were used as the input features. Seven popular machine learning algorithms were applied to the datasets to predict upper and lower lip prominence. The algorithm that performed the best was selected for the construction of the prediction model. Evaluation of feature importance was conducted using 3 classical methods. RESULTS: Among the 7 algorithms, the XGBoost model performed the best in the prediction of the distances between labrale superius or labrale inferius to the esthetics plane (UL-EP and LL-EP distances), with root mean square error values of 1.25, 1.49 and r2 values of 0.755 and 0.683, respectively. Among the 14 input features, the L1-NB distance contributed the most to the prominences of the upper and lower lips. A lip prominence predictor was developed to facilitate clinical application by deploying the prediction model into a downloadable tool kit. CONCLUSIONS: The XGBoost model performed well with high accuracy and practicability in predicting upper and lower lip prominence. The artificial intelligence-aided predictor could serve as a reference for orthodontic treatment planning.

Inhibition of TRIM32 by ibr-7 treatment sensitizes pancreatic cancer cells to gemcitabine via mTOR/p70S6K pathway.

Pancreatic cancer is one of the most notorious diseases for being asymptomatic at early stage and high mortality rate thereafter. However, either chemotherapy or targeted therapy has rarely achieved success in recent clinical trials for pancreatic cancer. Novel therapeutic regimens or agents are urgently in need. Ibr-7 is a novel derivative of ibrutinib, displaying superior antitumour activity in pancreatic cancer cells than ibrutinib. In vitro studies showed that ibr-7 greatly inhibited the proliferation of BxPC-3, SW1990, CFPAC-1 and AsPC-1 cells via the induction of mitochondrial-mediated apoptosis and substantial suppression of mTOR/p70S6K pathway. Moreover, ibr-7 was able to sensitize pancreatic cancer cells to gemcitabine through the efficient repression of TRIM32, which was positively correlated with the proliferation and invasiveness of pancreatic cancer cells. Additionally, knockdown of TRIM32 diminished mTOR/p70S6K activity in pancreatic cancer cells, indicating a positive feedback loop between TRIM32 and mTOR/p70S6K pathway. To conclude, this work preliminarily explored the role of TRIM32 in the malignant properties of pancreatic cancer cells and evaluated the possibility of targeting TRIM32 to enhance effectiveness of gemcitabine, thereby providing a novel therapeutic target for pancreatic cancer.

Investigated hydrogen-bond network kinetics of acetone-water solutions by spontaneous and stimulated Raman spectroscopy.

The hydrogen bond (HB) network structure and kinetics of the acetone-water mixed solutions were investigated by the spontaneous Raman and stimulated Raman scattering (SRS) spectra. The HB network of water molecules was enhanced when the volume fraction of acetone ranged from 0 to 0.25. Two new SRS peaks of water at 3272 and 3380 cm-1 were obtained, resulting from the cooperation of the polar carbonyl (C = O)-enhanced HB and the ice-like structure formed around the methyl groups. However, when the volume fraction went beyond 0.25, the spontaneous Raman main peak at 3445 cm-1 showed a significant blue-shift, and the corresponding SRS signal disappeared, indicating that the HB of water was weakened, which originated from the self-association of acetone. In the meantime, the fully tetrahedral HB structure among water molecules was destroyed at the higher volume fraction (≥ 0.8). Hopefully, our study here would advance the study of HB network structures and kinetics in other aqueous solutions.

Efficient frequency conversion and the crossing-pump effect of stimulated Raman scattering in an aqueous sodium sulfate solution.

The cascaded stimulated Raman scattering (SRS) of an aqueous sodium sulfate solution was investigated as well as the generation of the crossing-pump effect. With the introduction of dual sample cells, the first-order Stokes of the O-H stretching vibrational mode was able to act as the pump light to excite the Stokes of the S-O stretching vibrational mode, and a new Raman peak was obtained at 4423 cm-1. The dual sample cell device not only lowered the SRS threshold, but also enhanced the four-wave mixing (FWM) process. Compared to the input laser of 7 ns/pulse, the first-order Stokes of O-H was compressed to a pulse width of 413 ps after passing through the dual sample cells. The SRS of aqueous sodium sulfate solution covered an ultrabroad wavelength ranging from 441 nm to 720 nm (a Raman shift ranging from -3859 cm-1 to 4923 cm-1). The cone-shaped launch ring of the FWM process was also recorded. This work provides a reference for the establishment of laser frequency conversion devices using an aqueous sodium sulfate solution as the Raman medium.

Generation of dual-supercontinuum coherent radiation in acetone mixed with carbon disulfide by stimulated Raman scattering.

Stimulated Raman scattering (SRS) in a liquid has been a major focus of nonlinear optics. Traditional SRS generates single or cascaded Stokes components arising from spontaneous Raman noise. Herein, we report the formation mechanism of a specific spectrum-continuous spectroscopy technique based on SRS of mixed liquids. SRS of a mixed acetone and carbon disulfide solution is investigated by a pulsed Nd:YAG laser with a wavelength of 532 nm. Two remarkably asymmetric broadened SRS lines are obtained. When the volume ratio is 7:3, the broadened spectral bands are optimized. The supercontinuum spectroscopy phenomenon is explained by hydrogen bond formation, adjacent vibrational modes coupling, and laser-induced plasma generation. This technique has the potential to contribute to the development of a supercontinuum Raman laser.

A comparison of three preoperative nutritional assessment methods for predicting ovarian cancer patient prognosis: which is better?

BACKGROUND: The study aimed to compare the predictive values of three widely used nutritional assessment methods, body mass index (BMI), Nutritional Risk Screening 2002 (NRS 2002), and the prognostic nutritional index (PNI), for different clinical prognostic indicators of ovarian cancer patients. METHODS: Patients diagnosed with ovarian cancer treated in our hospital between January 2017 and March 2019 were retrospectively included. The three nutritional assessment methods were assessed, and multivariable analysis was conducted to explore predictive factors for clinical prognoses. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUROC) were generated to evaluate the discriminative abilities of the three nutritional assessment tools. RESULTS: A total of 442 patients were recruited. Multivariable analysis revealed that the PNI value predicted 1-year death and 1-year recurrence and that both the NRS 2002 score and the PNI value predicted 30-day readmission (P < 0.05). For PNI, AUROCs were 0.834 for predicting 1-year death and 0.719 for 1-year recurrence prediction; for NRS, the AUROC was 0.820 2002 for predicting 30-day readmission. The optimal cutoff values that maximized the prognostic prediction ability were PNI values of 47.75 g/L and 50.40 g/L for 1-year death and 1-year recurrence, respectively, and an NRS 2002 score of 3 points for 30-day readmission following discharge. CONCLUSION: For ovarian cancer patients, the PNI is better at predicting 1-year death and 30-day readmission after discharge, and the NRS 2002 is superior for predicting 1-year recurrence.

Exploring novel systemic therapies for pancreatic cancer: a review of emerging anti-PD-1/PD-L1 combination therapy.

Despite attempts to apply single therapy such as surgical treatment, chemotherapy, or radiotherapy, pancreatic cancer (PC) is still one of the most lethal solid tumors. Moreover, immune checkpoint inhibitors against PD-1/PD-L1, which have shown good efficacies against many other solid tumors, have not shown encouraging results in PC treatment. Therefore, some studies are evaluating the efficacies of combination therapies based on anti-PD-1/PD-L1 for PC. In this review, we summarized the emerging anti-PD-1/PD-L1 combination therapies for PC in these years. We realized that anti-PD-1/PD-L1-based combination therapies have the potential to be efficacious in PC treatment, and further relevant studies are needed. Moreover, we elucidated the reasons for the ineffectiveness of anti-PD-1/PD-L1 alone in PC treatment. We concluded that this was mainly because PC has an immunosuppressive tumor microenvironment and develops drug resistance during treatment. Anti-PD-1/PD-L1-based combination therapeutic regimens that alter the immunosuppressive tumor microenvironment and reduce the development of drug resistance in PC are summarized in this review, and we expect that these regimens will achieve good clinical application prospects.