Continuation of same programmed death-1 inhibitor regime beyond progression is a novel option for advanced gastric cancer.

BACKGROUND: Gastric cancer is a significant global malignancy with poor prognosis. Although the emergence of immune checkpoint inhibitors (ICIs) prolonged the duration of survival, resistance and progression are inevitable. We aim to evaluate the effectiveness of programmed death-1 (PD-1) inhibitors in immunotherapy beyond progression (IBP). METHOD: We divided the advanced gastric cancer patients who received two lines immunotherapy into same regimen group (with same PD-1 inhibitor regime after IBP) and different regimen group (with different PD-1 inhibitor regime after IBP). Statistical analysis conducted to compare patient characteristics and evaluate survival differences between groups. RESULT: The clinical outcome analysis showed that the same PD-1 inhibitor regime seemed to exhibit a higher disease control rate (DCR) (51.8% vs. 29.2%, P = 0.062), significantly prolonged progression-free survival 2 (PFS2) (162 vs. 75 days, P = 0.001) and overall survival (OS) (312 vs. 166 days, P = 0.022) when compared with those of cross line. In the multivariate analysis, when using different regimen group as reference, the same regimen group was found to be independently associated with improved PFS2 [hazard ratio (HR) = 0.467, 95% confidence interval (CI): 0.267-0.816, P = 0.008] and OS (HR = 0.508, 95%CI: 0.278-0.927, P = 0.027). CONCLUSION: Continuation of the same type of PD-1 inhibitor regime in IBP shows clinical benefits and represents a promising therapeutic approach.

Alpha-fetoprotein predicts the treatment efficacy of immune checkpoint inhibitors for gastric cancer patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are commonly used in conjunction with chemotherapy to improve treatment outcomes for patients with gastric cancer. Since AFP could influence immunity by both inhibiting natural killer (NK) cells and regulating negatively the function of dendritic cells, we evaluated the influence of baseline serum alpha-fetoprotein (AFP) levels on the curative effect of ICIs in advanced gastric cancer (AGC) patients. METHODS: A retrospective analysis was conducted on 158 AGC patients who underwent ICI treatment. The patients were divided into high and low groups based on the AFP threshold of 20 ng/ml. The efficacy of ICI treatment was assessed using objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). RESULTS: The higher levels of baseline AFP were found to be associated with a decrease in the effectiveness of ICIs, as evidenced by a DCR of 50.0% in the group with high AFP levels compared to 87.7% in the group with low AFP levels (P < 0.001). Further analysis using Kaplan-Meier survival techniques indicated that a high AFP level was linked to shorter progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.001) in AGC individuals receiving ICIs. After propensity score matching, a log rank test revealed that the high AFP group had a decrease in median PFS (P = 0.011) and median OS (P = 0.036) compared to the low AFP group. The high AFP levels also showed its association with shorter PFS and OS in the subgroup analysis of ICI plus chemotherapy patients. CONCLUSIONS: Baseline AFP levels may predict immune checkpoint inhibitor treatment efficacy in AGC patients.

Respiratory pathogenic microbial infections: a narrative review.

Respiratory infectious diseases have long been recognised as a substantial global healthcare burden and are one of the leading causes of death worldwide, particularly in vulnerable individuals. In the post COVID-19 era, there has been a surge in the prevalence of influenza virus A and other multiple known viruses causing cold compared with during the same period in the previous three years, which coincided with countries easing COVID-19 restrictions worldwide. This article aims to review community-acquired respiratory illnesses covering a broad spectrum of viruses, bacteria, and atypical microorganisms and focuses on the cluster prevalence of multiple known respiratory pathogens in China, thereby providing effective prevention and control measures.

Highly Sensitive and Selective Detection of Formaldehyde via Bio-Electrocatalysis over Aldehyde Dehydrogenase.

Formaldehyde (HCHO), as one of the prominent indoor pollutants, causes many health-related problems. Although the detection of HCHO is a widespread concern and a variety of detection methods have been continuously developed, the volatile organic chemical (VOC) interference remains to be solved. Here, we report a highly sensitive and selective method for HCHO detection, relying on the selective electrochemical oxidation of formaldehyde catalyzed by aldehyde dehydrogenases (ALDHs) on a Cu electrode. The detection signal exhibits a standard power law relationship against the analytes with a broad detection range of 10-5-10-15 M and a limit of detection (LOD) of 1.46 × 10-15 M, far below the indoor safe exposure limit (about 10-9 M) for formaldehyde. In comparison to the standard spectrophotometry method, the ALDH-based electrochemical method shows a much high specificity to formaldehyde among common VOCs, such as benzene, toluene, and xylene. This simple yet effective detection technique opens up a new path for developing advanced formaldehyde sensors with high sensitivity and selectivity.

Are anti-PD-1-associated immune related adverse events a harbinger of favorable clinical prognosis in patients with gastric cancer?

BACKGROUND: Immune checkpoint inhibitors (ICIs) has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate immune related adverse events (irAEs) in patients. Some studies have shown that there is a close relationship between the occurrence of irAEs and prognosis. In present study, we have attempted to establish whether the occurrence of irAEs after the use of anti PD-1 antibodies is associated with treatment efficacy in people with advanced gastric cancer (AGC). METHODS: This study included patients treated with the anti-PD-1 antibodies for AGC patients at The Fourth Hospital of Hebei Medical University. IrAEs were identified clinically and graded as per the National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.03. Efficacy was evaluated with objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS). The analysis was performed to determine the association between irAEs and clinical outcomes. RESULT: Of the 74 AGC patients in our study, 24 developed irAEs. The DCR of the irAE displayed a trend better than that of non-irAE group but without statistical difference (41.70% VS 6.0%, p = 0.118). Median PFS in the irAE group was superior to that in the non-irAE group (176 days VS 94 days, p = 0.001). Median OS also showed this trend of difference at borderline statistical level (292 days VS 239 days, p = 0.057). Multivariate analysis also demonstrated irAE (HR = 0.269, 95%CI: 0.088 to 0.822, p = 0.021) were associated independently with the better prognosis for AGC patients. CONCLUSION: In advanced gastric cancer treated with anti PD-1 antibodies, the occourence of irAEs might contribute to the improved prognosis.

Prevalence and factors associated with overweight or obesity among 2- to 6-year-old children in Hunan, China: a cross-sectional study.

OBJECTIVE: To compare the prevalence of overweight or obesity (ow/ob) with WHO BMI cut-off points, International Obesity Task Force (IOTF) cut-off points and Chinese BMI criteria and examine its potential factors among preschool children in Hunan Province. DESIGN: A cross-sectional survey including anthropometric measurements and questionnaires about children's information, caregivers' socio-demographic characteristics and maternal characteristics. χ2 tests and univariate and multivariate binary logistic regression were performed to evaluate the possible factors of ow/ob. SETTING: Hunan, China, from September to October 2019. PARTICIPANTS: In total, 7664 children 2 to 6 years of age. RESULTS: According to Chinese BMI criteria, about 1 in 7-8 children aged 2-6 years had ow/ob in Hunan, China. The overall estimated prevalence of ow/ob among 2- to 6-year-old children was significantly higher when based on the Chinese BMI criteria compared with the WHO BMI cut-off points and IOTF cut-off points. According to Chinese BMI criteria, ow/ob was associated with residing in urban areas, older age, male sex, eating snacking food more frequently, macrosomia delivery, caesarean birth, heavier maternal prepregnancy weight and pre-delivery weight. CONCLUSION: The prevalence of ow/ob in preschool children in Hunan Province remains high. More ow/ob children could be screened out according to Chinese BMI cut-offs compared with WHO and IOTF BMI criteria. In the future, targeted intervention studies with matched controls will be needed to assess the long-term effects of intervention measures to provide more information for childhood obesity prevention and treatment.

Calcium, conformational selection, and redox-active tyrosine YZ in the photosynthetic oxygen-evolving cluster.

In Photosystem II (PSII), YZ (Tyr161D1) participates in radical transfer between the chlorophyll donor and the Mn4CaO5 cluster. Under flashing illumination, the metal cluster cycles among five Sn states, and oxygen is evolved from water. The essential YZ is transiently oxidized and reduced on each flash in a proton-coupled electron transfer (PCET) reaction. Calcium is required for function. Of reconstituted divalent ions, only strontium restores oxygen evolution. YZ is predicted to hydrogen bond to calcium-bound water and to His190D1 in PSII structures. Here, we report a vibrational spectroscopic study of YZ radical and singlet in the presence of the metal cluster. The S2 state is trapped by illumination at 190 K; flash illumination then generates the S2YZ radical. Using reaction-induced FTIR spectroscopy and divalent ion depletion/substitution, we identify calcium-sensitive tyrosyl radical and tyrosine singlet bands in the S2 state. In calcium-containing PSII, two CO stretching bands are detected at 1,503 and 1,478 cm-1 These bands are assigned to two different radical conformers in calcium-containing PSII. At pH 6.0, the 1,503-cm-1 band shifts to 1,507 cm-1 in strontium-containing PSII, and the band is reduced in intensity in calcium-depleted PSII. These effects are consistent with a hydrogen-bonding interaction between the calcium site and one conformer of radical YZ. Analysis of the amide I region indicates that calcium selects for a PCET reaction in a subset of the YZ conformers, which are trapped in the S2 state. These results support the interpretation that YZ undergoes a redox-coupled conformational change, which is calcium dependent.

Tracking Reactive Water and Hydrogen-Bonding Networks in Photosynthetic Oxygen Evolution.

In oxygenic photosynthesis, photosystem II (PSII) converts water to molecular oxygen through four photodriven oxidation events at a Mn4CaO5 cluster. A tyrosine, YZ (Y161 in the D1 polypeptide), transfers oxidizing equivalents from an oxidized, primary chlorophyll donor to the metal center. Calcium or its analogue, strontium, is required for activity. The Mn4CaO5 cluster and YZ are predicted to be hydrogen bonded in a water-containing network, which involves amide carbonyl groups, amino acid side chains, and water. This hydrogen-bonded network includes amino acid residues in intrinsic and extrinsic subunits. One of the extrinsic subunits, PsbO, is intrinsically disordered. This extensive (35 Å) network may be essential in facilitating proton release from substrate water. While it is known that some proteins employ internal water molecules to catalyze reactions, there are relatively few methods that can be used to study the role of water. In this Account, we review spectroscopic evidence from our group supporting the conclusion that the PSII hydrogen-bonding network is dynamic and that water in the network plays a direct role in catalysis. Two approaches, transient electron paramagnetic resonance (EPR) and reaction-induced FT-IR (RIFT-IR) spectroscopies, were used. The EPR experiments focused on the decay kinetics of YZ• via recombination at 190 K and the solvent isotope, pH, and calcium dependence of these kinetics. The RIFT-IR experiments focused on shifts in amide carbonyl frequencies, induced by photo-oxidation of the metal cluster, and on the isotope-based assignment of bands to internal, small protonated water clusters at 190, 263, and 283 K. To conduct these experiments, PSII was prepared in selected steps along the catalytic pathway, the Sn state cycle (n = 0-4). This cycle ultimately generates oxygen. In the EPR studies, S-state dependent changes were observed in the YZ• lifetime and in its solvent isotope effect. The YZ• lifetime depended on the presence of calcium at pH 7.5, but not at pH 6.0, suggesting a two-donor model for PCET. At pH 6.0 or 7.5, barium and ammonia both slowed the rate of YZ• recombination, consistent with disruption of the hydrogen-bonding network. In the RIFT-IR studies of the S state transitions, infrared bands associated with the transient protonation and deprotonation of internal waters were identified by D2O and H218O labeling. The infrared bands of these protonated water clusters, Wn+ (or nH2O(H3O)+, n = 5-6), exhibited flash dependence and were produced during the S1 to S2 and S3 to S0 transitions. Calcium dependence was observed at pH 7.5, but not at pH 6.0. S-state induced shifts were observed in amide C═O frequencies during the S1 to S2 transition and attributed to alterations in hydrogen bonding, based on ammonia sensitivity. In addition, isotope editing of the extrinsic subunit, PsbO, established that amide vibrational bands of this lumenal subunit respond to the S state transitions and that PsbO is a structural template for the reaction center. Taken together, these spectroscopic results support the hypothesis that proton transfer networks, extending from YZ to PsbO, play a functional and dynamic role in photosynthetic oxygen evolution.

Identification of sequence polymorphisms in the mitochondrial cytochrome c oxidase genes as risk factors for hepatocellular carcinoma.

BACKGROUND: Single nucleotide polymorphisms (SNPs) accumulated in the mitochondrial DNA (mtDNA) is susceptible to the tumor formation. We discovered previously that SNPs in the mitochondrial displacement loop (D-loop) was associated with the risk of hepatocellular carcinoma (HCC). METHODS: The cytochrome c oxidase (COX) genes of mtDNA were sequenced between 107 HCC patients and 100 matched healthy controls. The χ2 test was used to analyze single SNPs' statistical difference between HCC patients and healthy controls. RESULTS: In this study, cancer risk-associated SNPs in the COX genes of mtDNA coding region were assessed in HCC patients and health controls. The nucleotide position at site 9545A/G (P=.036) was identified its association for HCC with the 9545G allele susceptible to cancer risk. CONCLUSIONS: The SNPs in the COX genes may help us to evaluate the cancer risk of HCC.

Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA is associated with the kidney survival time in chronic kidney disease patients.

BACKGROUND: The mitochondrial displacement loop (D-loop) is known to accumulate mutations and SNPs at a higher frequency than other regions of mitochondrial DNA (mtDNA). We had identified chronic kidney disease (CKD) risk-associated SNPs in the D-loop of CKD patients previously. In this study, we investigated the association of SNPs in the D-loop of mtDNA with the kidney survival of CKD. METHODS: The D-loop region of mtDNA was sequenced for 119 CKD patients from the inpatient of the Fourth Hospital of Hebei Medical University. The Kaplan-Meier method was used to identify disease outcome-associated SNPs in the D-loop of CKD patients. The Cox proportional hazards model was used to identify risk factors for the kidney survival of CKD. RESULTS: In the present study, we identified 20 SNPs with a frequency higher than 5% and assessed the relationship of these SNPs with kidney survival time in CKD patients, a SNP of 146 was identified by log-rank test for statistically significant prediction of the kidney survival time. In an overall multivariate analysis, allele 146 was identified as an independent predictor of kidney survival time in CKD patients. The survival time of kidney in the CKD patients with 146C was significantly shorter than that of kidney in CKD patients with 146T (relative risk, 2.336; 95% CI, 1.319-3.923; p = 0.001). CONCLUSION: SNPs in the D-loop can predict the kidney survival of CKD patients. Analysis of genetic polymorphisms in the mitochondrial D-loop can help to identify CKD patient subgroup at high risk of a poor disease outcome.

X protein mutations in hepatitis B virus DNA predict postoperative survival in hepatocellular carcinoma.

Hepatitis B virus (HBV) DNA is prone to mutations because of the proofreading deficiencies of HBV polymerase. The postoperative prognostic value of HBV mutations in HBV X protein (HBx) gene was assessed in HBV associated hepatocellular carcinoma (HCC) patients. The HBx gene was amplified and sequenced, the HBV mutations was identified according to NCBI database ( http://www.ncbi.nlm.nih.gov/genome/5536 ). The relationship between the HBV mutations and HCC survival was compared. Survival curves were generated using the Kaplan-Meier method, and comparisons between the curves were made using the log-rank test. Multivariate survival analysis was performed using a Cox proportional hazards model. After adjusting for clinical characteristics, the following eight mutational sites were identified as statistically significant independent predictors of HCC survival: 1383, 1461, 1485, 1544, 1613, 1653, 1719, and 1753. In addition, the following four mutational sites were identified for their association with survival at a border-line significance level: 1527, 1637, 1674, and 1762/1764. A total of 12 mutations in HBx gene region were identified as independent predictors of postoperative survival in HCC patients. The analysis of HBV DNA mutations may help identify patient subgroups with poor prognosis and may help refine therapeutic decisions regarding HCC patients.

Identification of sequence polymorphisms in the mitochondrial displacement loop as risk factors for sporadic and familial breast cancer.

The accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been described for different types of cancers, and the association of these SNPs with cancer risk and disease outcome has been exhaustively studied. We sequenced a region of approximately 1 kb flanking the majority of the D-Loop in the DNA from the blood of breast cancer patients and the controls to identify cancer risk-associated D-loop SNPs. The D-loop region of mtDNA was sequenced from 92 sporadic breast cancer patients, 60 familial breast cancer patients and 41 relatives, and 93 healthy controls. Paired and unpaired Student's t tests were used as appropriate to determine the differences in SNP distribution within the D-loop region and in the number of SNPs per patient among the groups. The χ (2) test was used to analyze dichotomous values, such as the presence or absence of an individual SNP among each group, and the clinical characteristics between every two groups. The distribution frequencies of 315C/Cinsert, 524C/del, 16247A/del, 16248C/del, 16249T/C, 16257C/A, 16258A/del, 16259C/del, 16262C/del, 16268C/del, 16279C/del, 16280A/del, 16297T/C, and 16300A/del were significantly different between sporadic breast cancer patients and the normal controls. The SNP sites at nucleotides 310, 315, and 16362 were identified as cancer risk-associated SNPs specific for familial breast cancer. The N haplogroup, defined as 489T, was identified as a specific risk-associated SNP for families of breast cancer patients by comparing familial breast cancer patients with their relatives. The analysis of genetic polymorphisms in the D-loop may help to predict cancer risk for familial breast cancer and thereby help to detect and refine therapeutic decisions earlier.

Mitochondrial DNA haplogroup N is associated good outcome of gastric cancer.

Accumulation of mutations and single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been identified for their association with cancer risk and disease outcome in a variety of cancers. We have identified cancer risk-associated D-loop SNPs in gastric cancer patients. In this study, we evaluated the predictive value of these SNPs for cancer outcome. Two SNP sites of nucleotides 489C/T and 523-524AC/del were identified for statistically significant prediction of postoperative survival in gastric cancer by univariate analysis with log-rank test. In addition, the mitochondrial DNA haplogroup N (489T) contributed to the good survival of gastric cancer patients compared with the mitochondrial DNA haplogroup M (489C) genotype (relative risk, 1.753; 95 %CI, 1.005-3.060; p = 0.048) by multivariate analysis with COX hazards model. In conclusion, analysis of genetic polymorphisms in the mitochondrial D-loop can help identify subgroups of patients who are at a high risk of a poor disease outcome.

Association of sequence polymorphism in the mitochondrial D-loop with chronic kidney disease.

BACKGROUND: The mitochondrial displacement loop (D-loop) is known to accumulate mutations and single nucleotide polymorphisms (SNPs) at a higher frequency than other regions of mitochondrial DNA (mtDNA). METHODS: This is a case-control study. We sequenced SNPs in the D-loop of mtDNA and investigated their association with the risk of chronic kidney disease (CKD). RESULTS: A total of 144 SNPs referring to the positions of the Revised Cambridge Reference Sequence (rCRS) for mitochondrial genome were identified in a case-control study. The minor alleles of nucleotides 73G, 146C, 150T, 194T, 195C and 310C were associated with an increased risk for CKD patients. CONCLUSION: Analysis of genetic polymorphisms in the mitochondrial D-loop can help identify the people who are at a high risk of developing chronic kidney disease. These SNPs can be considered as potential predictors for CKD.

Glutathione ligand self-assembly enables luminescence from Au15 nanoclusters for highly sensitive and selective monitoring of blood Pb(II) ions.

Lead Pb(II) ions is a cumulative toxicant that impacts several biological systems and poses severe harm to young children. Accurate Pb(II) ions monitoring is thus of paramount importance. Here, we present the synthesis and application of glutathione-capped Au15 nanoclusters (Au15(SG)13) as a luminescence probe for the accurate and selective monitoring of blood Pb(II). The introduction of Pb(II) ions triggers orderly self-assembly of Au15 nanoclusters, resulting in the formation of rigid shell around Au nuclei. This limits the localized vibration of the glutathione ligands and their interaction with water molecules, greatly reducing non-radiative energy loss, and thereby enhancing the photoluminescence signal. Consequently, Au15(SG)13 nanoclusters exhibit high sensitivity for Pb(II) detection. The detection signal displays a linear relationship with Pb(II) over a wide detection range (0-800 µg/L), demonstrating a substantial sensitivity of 35.29 µg/L. Moreover, the developed nanoclusters show superior selectivity for Pb(II) ions, distinguishing them from other prevalent heavy metals. This work pave the way for the development of advanced Pb(II) sensors with high sensitivity and selectivity.

Bioinspired Hierarchical Self-Assembled Nanozyme for Efficient Antibacterial Treatment.

Along with the rapid development and ever-deepening understanding of nanoscience and nanotechnology, nanomaterials hold promise to mimic the highly evolved biological exquisite nanostructures and sophisticated functions. Here, inspired by the ubiquitous antibacterial nanostructures on the wing surfaces of some insects, a NiCo2 O4 nanozyme with self-adaptive hierarchical nanostructure is developed that can capture bacteria of various morphotypes via the physico-mechanical interaction between the nanostructure and bacteria. Moreover, the developed biomimetic nanostructure further exhibits superior peroxidase-like catalytic activity, which can catalytically generate highly toxic reactive oxygen species that disrupt bacterial membranes and induce bacterial apoptosis. Therefore, the mechano-catalytic coupling property of this NiCo2 O4 nanozyme allows for an extensive and efficient antibacterial application, with no concerns of antimicrobial resistance. This work suggests a promising strategy for the rational design of advanced antibacterial materials by mimicking biological antibiosis.

Clinical biomarkers for thyroid immune-related adverse events in patients with stage III and IV gastrointestinal tumors.

Background: Thyroid immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) treatment appear to correlate with a better prognosis. We aimed to investigate clinical biomarkers associated with thyroid irAEs. Methods: We retrospectively analyzed data from 129 patients receiving programmed cell death protein 1 (PD-1) inhibitors for stage III and IV gastrointestinal tumors. Patients were divided into two groups: "thyroid irAEs" group and "no thyroid irAEs" group. We compared continuous variables using Mann-Whitney U and Kruskal-Wallis tests and categorical variables using Pearson's chi-square test. Survival curves were generated using the Kaplan-Meier method, and associations between clinical features and thyroid irAEs were assessed using univariate and multivariate logistic regression models. Associations for thyroid irAEs and outcomes [progression-free survival (PFS), overall survival (OS)] of the patients were performed with a Cox proportional hazard model. Results: A total of 129 patients, including 66 gastric cancer, 30 esophageal squamous cell carcinoma, and 33 hepatocellular carcinoma (HCC), were involved in this analysis with 47 cases of thyroid irAEs occurrence. The Cox proportional hazard model analysis confirmed the extended PFS [hazard rate (HR) = 0.447, 95% confidence interval (CI): 0.215 to 0.931, p = 0.031] and OS (HR = 0.424, 95% CI: 0.201 to 0.893, p = 0.024) for thyroid irAEs group when compared with those of the no thyroid irAEs group. Association between thyroid irAEs and clinical characteristics at baseline was analyzed subsequently by univariate analysis. Higher body mass index (p = 0.005), increased eosinophil count (p = 0.014), increased lactate dehydrogenase (p = 0.008), higher baseline thyroid stimulating hormone (TSH) (p = 0.001), HCC (p = 0.001) and increased adenosine deaminase (ADA) (p = 0.001) were linked with thyroid irAEs occurrence. The multivariable logistic regression model indicated that ADA [odds rate (OR) = 4.756, 95% CI: 1.147 to 19.729, p = 0.032] was independently associated with thyroid irAEs occurrence. Conclusions: Increased baseline level of ADA was associated with thyroid irAEs occurrence in patients with advanced gastrointestinal tumors who received ICI treatment. In the case of abnormal ADA, attention should be paid to the risk of thyroid irAEs.

Immune-Related Adverse Event-Related Adrenal Insufficiency Mediates Immune Checkpoint Inhibitors Efficacy in Cancer Treatment.

Purpose: Immune checkpoint inhibitors (ICIs) have significantly improved the outcomes of patients with cancer; however, these agents may initiate immune-related adverse events (irAEs). Previous studies have demonstrated a robust correlation between disease prognosis and the occurrence of irAEs, specifically skin or endocrine irAEs. Herein, we aimed to evaluate the correlation between irAE-related adrenal insufficiency (AI) and ICI treatment efficacy. Patients and methods: Patients diagnosed with gastrointestinal, respiratory, head and neck, urological, skin and gynecologic cancers treated with anti-programmed cell death 1 (PD-1)/anti-programmed cell death ligand 1 (PD-L1) antibody as monotherapy or combined therapy (combined with chemotherapy or targeted therapy) were divided into irAE-A (patients with irAE-related AI), irAE-B (patients with other irAEs) and non-irAE groups. Immunotherapy efficacy was assessed based on the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Survival probabilities were estimated using the Kaplan-Meier method with the log-rank test. Results: Of the 192 patients enrolled in our study, 17 developed irAE-related AI and 83 developed other irAEs. The DCR of the irAE-A and irAE-B groups were higher than that of the non-irAE group (P<0.05). Multiple extended Cox regression analyses showed that irAE status (irAE-A vs non-irAE, P=0.008; irAE-B vs non-irAE, P=0.020), Eastern Cooperative Oncology Group (ECOG) status (P=0.045), tumor-node-metastasis (TNM) stage (P=0.000), and treatment line (P=0.002) were independent predictors of PFS. Contrarily, irAE status (irAE-A vs non-irAE, P=0.009; irAE-B vs non-irAE, P=0.013), ECOG status (P=0.007), TNM stage (P=0.035), treatment line (P=0.001) and treatment modality (P=0.008) were independent predictors for OS. Conclusion: IrAE-related AI was significantly associated with ICI treatment efficacy in patients with cancer, which could be a potentially predictable marker. Due to the destruction of adrenal tissue by T cells with enhanced activity, AI reflects enhanced T cell activity to some extent.

Sirtuin-3 (SIRT3) expression is associated with overall survival in esophageal cancer.

Sirtuin-3 (SIRT3) was immunostained in 94 samples of esophageal cancer tissues and semiquantified using the HSCORE method to evaluate the predictive value of SIRT3 expression levels on esophageal cancer outcome. The relationship between SIRT3 expression and the 5-year survival rate of postoperational esophageal cancer patients was assessed with the Kaplan-Meier method. High expression of SIRT3 is associated with a shorter survival time in esophageal cancer patients, as shown by the log-rank test (P = .007), and the level of SIRT3 expression was identified as an independent predictor for esophageal cancer outcome using Cox proportional hazards model analysis (relative risk, 2.061; 95% confidence interval, 1.050-4.046; P = .036). SIRT3 expression was associated with esophageal cancer outcome. The analysis of SIRT3 levels can help in the identification of patient subgroups that are at high risk for poor disease outcomes.

Recent progress in single-atom nanozymes research.

Single-atom nanozyme (SAzyme) is the hot topic of the current nanozyme research. Its intrinsic properties, such as high activity, stability, and low cost, present great substitutes to natural enzymes. Moreover, its fundamental characteristics, i.e., maximized atom utilizations and well-defined geometric and electronic structures, lead to higher catalytic activities and specificity than traditional nanozymes. SAzymes have been applied in many biomedical areas, such as anti-tumor therapy, biosensing, antibiosis, and anti-oxidation therapy. Here, we will discuss a series of representative examples of SAzymes categorized by their biomedical applications in this review. In the end, we will address the future opportunities and challenges SAzymes facing in their designs and applications.