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The mutual regulation between hydrogen sulfide (H2S) and microRNA (miRNA) is involved in the development of many diseases, including cancer, cardiovascular disease, inflammatory disease, and high-risk pregnancy. Abnormal expressions of endogenous H2S-producing enzyme and miRNA in tissues and cells often indicate the occurrence of diseases, so the maintenance of their normal levels in the body can mitigate damages caused by various factors. Many studies have found that H2S can promote the migration, invasion, and proliferation of cancer cells by regulating the expression of miRNA, while many H2S donors can inhibit cancer progression by interfering with the proliferation, apoptosis, cell cycle, metastasis, and angiogenesis of cancer cells. Furthermore, the mutual regulation between H2S and miRNA can also prevent cell injury in cardiovascular disease and inflammatory disease through anti-inflammation, anti-oxidation, anti-apoptosis, and pro-autophagy. In addition, H2S can promote angiogenesis and relieve vasoconstriction by regulating the expression of miRNA, thereby improving fetal growth in high-risk pregnancy. In this review, we discuss the mechanism of mutual regulation between H2S and miRNA in various diseases, which may provide reliable therapeutic targets for these diseases.

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In recent years, the impact of age-related diseases on human health has become increasingly severe, and developing effective drugs to deal with these diseases has become an urgent task. Considering the essential regulatory role of hydrogen sulfide (H2S) in these diseases, it is regarded as a promising target for treatment. H2S is a novel gaseous transmitter involved in many critical physiological activities, including anti-oxidation, anti-inflammation, and angiogenesis. H2S also regulates cell activities such as cell proliferation, migration, invasion, apoptosis, and autophagy. These regulatory effects of H2S contribute to relieving and treating age-related diseases. In this review, we mainly focus on the pathogenesis and treatment prospects of H2S in regulating age-related diseases.

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BACKGROUND: Glutathione (GSH), a highly abundant thiol compound within cells, plays a critical role in physiological processes and exhibits close correlation with cancer. Among molecular imaging technologies, most probes have relatively short emission wavelengths and lack photoacoustic imaging (PA) capability, resulting in the inability to obtain tissue images with high penetration depth. The presence of GSH in the tumor microenvironment neutralizes ROS, diminishing the therapeutic effect of PDT, thus resulting in often unsatisfactory therapeutic efficacy. Therefore, it is imperative to develop a dual-modal probe for the detection of GSH and the diagnosis and treatment of cancer. RESULTS: In this study, we synthesized a novel dual-modal probe, Cy-Bio-GSH, utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging techniques for GSH detection. The probe integrates cyanine dye as the fluorophore, nitroazobenzene as the recognition moiety, and biotin as the tumor-targeting moiety. Upon reacting with GSH, the probe emits NIR fluorescence at 820 nm and generates a PA signal. Significantly, this reaction activates the photodynamic and photothermal properties of the probe. By depleting GSH and employing a synergistic photothermal therapy (PTT) treatment, the therapeutic efficacy of photodynamic therapy (PDT) is remarkably enhanced. In-vivo experiments confirm the capability of the probe to detect GSH via NIRF and PA imaging. Notably, the combined tumor-targeting ability and PDT/PTT synergistic therapy enhance therapeutic outcomes for tumors and facilitate their ablation. SIGNIFICANCE: A novel tumor-targeting and dual-modal imaging probe (Cy-Bio-GSH) is synthesized, exhibiting remarkable sensitivity and selectivity to GSH, enabling the visualization of GSH in cells and the differentiation between normal and cancer cells. Cy-Bio-GSH enhances PDT/PTT with effective killing of cancer cells and makes the ablation of tumors in mice. This work represents the first tumor-targeting probe for GSH detection, and provides crucial tool for cancer diagnosis and treatment by dual-modal imaging with improved PDT/PTT synergistic therapy.

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A near-infrared fluorescent probe (TX-P) for detecting peroxynitrite is constructed. The probe has a near-infrared emission (725 nm), large Stokes shift (125 nm) and excellent sensitivity and selectivity. In addition, TX-P can be used to visualize ONOO- in living cells, image ONOO- in paw edema mice and evaluate anti-inflammatory drugs.

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BACKGROUNDS: The efficacy of endoscopic submucosal dissection (ESD) to treat poorly differentiated superficial esophageal squamous cell carcinoma (SESCC) is unclear. AIMS: To exploring the efficacy and prognosis of ESD treatment poorly differentiated SESCC compared with esophagectomy. METHODS: A retrospective cohort study was conducted, the data of poorly differentiated SESCC patients who received ESD or esophagectomy from Jan 2011 to Jan 2021 were analyzed. Overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and procedure-related variables were compared between ESD and esophagectomy group. RESULTS: 95 patients underwent ESD, while 86 underwent esophagectomy. No significant differences were found between the two groups in OS (P = 0.587), DSS (P = 0.172), and RFS (P = 0.111). Oncologic outcomes were also similar between the two groups in propensity score-matched analysis. For T1a ESCC, the rates of R0 resection, LVI or nodal metastasis and additional therapy were similar between ESD and esophagectomy groups. But for T1b ESCC, the rates of positive resection margin and additional therapy were significantly higher in ESD group than those in esophagectomy group. CONCLUSIONS: ESD is a minimally invasive procedure that has comparable oncologic outcomes with esophagectomy for treatment poorly differentiated T1a ESCC. However, ESD is not suitable for poorly differentiated T1b ESCC, additional surgery or radiochemotherapy should be required.

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Fatty liver disease affects at least 25 percent of the population worldwide and is a severe metabolic syndrome. Viscosity is closely related to fatty liver disease, so it is urgent to develop an effective tool for monitoring viscosity. Herein, a NIR fluorescent probe called MBC-V is developed for imaging viscosity, consisting of dimethylaniline and malonitrile-benzopyran. MBC-V is non-fluorescent in low viscosity solutions due to intramolecular rotation. In high viscosity solution, the intramolecular rotation of MBC-V is suppressed and the fluorescence is triggered. MBC-V has long emission wavelength at 720 nm and large Stokes shift about 160 nm. Moreover, MBC-V can detect changes in cell viscosity in fatty liver cells, and can image the therapeutic effects of drug in fatty liver cells. By taking advantage of NIR emission, MBC-V can be used as an imaging tool for fatty liver disease and a way to evaluate the therapeutic effect of drug for fatty liver disease.

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AIMS: To study the effects of a bridging dose of U-100 glargine (U-100G) with the first dose of degludec in type 1 diabetes (T1D) patients transitioning from glargine to degludec, by comparing the glucose metrics 48 h before and after the transition. MATERIALS AND METHODS: Patients with T1D on a stable U-100G regimen and with glycated haemoglobin concentration <75 mmol/mol were randomized (double-blind) to one dose of placebo or U-100G with first dose of degludec, administered at 9:00 pm. Patients on once-daily U-100G at baseline received 50% of total U-100G dose (bridging dose), while patients on twice-daily U-100G received 50% of the evening U-100G dose. Participants wore a continuous glucose monitor during the study. RESULTS: Forty participants were randomized, of whom 37 completed the study. The cohort was 65% male, the mean age was 47 years, duration of T1D 22 years, BMI 26 kg/m2, HbA1c 51 mmol/mol and total daily insulin dose 0.7 units/kg body weight. The bridging group included 19 participants (once-daily U-100G: n = 12; twice-daily U-100G: n = 7) and the placebo group included 18 participants (once-daily U-100G: n = 12; twice-daily U-100G: n = 6). Change in time in range (TIR) was not significantly different between the two treatment groups. In secondary analyses, among twice-daily U-100G users, TIR (3.9-10 mmol/L) increased 8% in the bridging group in the 48 h after first dose of degludec compared to the preceding 48 h, while participants in the placebo group had a 9.5% decrease (p = 0.027). CONCLUSIONS: A subgroup of well-controlled twice-daily U-100G users transitioning to degludec benefited from a 50% bridging dose of evening U-100G with the first dose of degludec in a small pilot study.

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Malglycemia, defined as hyperglycemia, hypoglycemia, or increased glycemic variability, has been associated with increased mortality after allogeneic hematopoietic cell transplantation (HCT). Among critically ill non-HCT recipients with diabetes and poor glycemic control, compared to those without diabetes, stringent blood glucose control has been associated with increased mortality. This study investigated whether a pre-HCT diagnosis of diabetes and the type of pre-HCT diabetes treatment modulate the previously reported negative impact of malglycemia on post-HCT nonrelapse mortality (NRM). We performed a single-institution retrospective analysis of mortality outcomes after allogeneic HCT as a function of post-HCT blood glucose levels, pre-HCT diagnosis of diabetes, and type of pre-HCT diabetes treatment (insulin, no insulin). A total of 1062 patients who underwent allogeneic HCT between 2015 and 2020 were included in this study. Among these patients, 84 (8%) had a pre-HCT diagnosis of diabetes, of whom 38 (4%) used insulin and 46 (4%) used a noninsulin antiglycemic agent. Post-HCT blood glucose values measured within 100 days from HCT, modeled as a continuous nonlinear time-varying covariate, were associated with day-200 NRM, with both lower and higher glycemic values associated with higher NRM compared to normoglycemic values (adjusted P < .0001). The association between post-HCT blood glucose and NRM varied, however, depending on the presence or absence of a pre-HCT diagnosis of diabetes; that is, there was evidence of a statistical interaction between blood glucose levels and diabetes (adjusted P = .008). In particular, the detrimental impact of hyperglycemic values was more pronounced in patients without a pre-HCT diagnosis of diabetes compared to those with a pre-HCT diagnosis of diabetes. As reported previously, higher and lower blood glucose levels measured within 100 days after allogeneic HCT were associated with an increased risk of NRM; however, this association was more pronounced among patients without a pre-HCT diagnosis of diabetes compared to those with a pre-HCT diagnosis of diabetes, suggesting that patients with diabetes are relatively protected from the downstream effects of hyperglycemia. These data support the notion that patients with pre-HCT diabetes may need a different approach to blood glucose management after transplantation compared to those without diabetes. © 2024 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

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As a basic parameter of the intracellular microenvironment, viscosity is closely related to the development of cancer. Thus, it is necessary to utilize a sensitive tool to visualize the viscosity in tumor cells and mice, which is helpful for the diagnosis of cancer. Herein, a novel dual-modal probe (IX-V) that has a near-infrared fluorescence (NIRF) and photoacoustic (PA) response to viscosity is synthesized. In low viscosity media, the probe has no fluorescence. With the increase of viscosity, the fluorescence is produced in the near-infrared region due to the inhibition of the TICT process. At the same time, the probe shows different photoacoustic (PA) signals in different viscosity media. Most notably, the viscosity in tumor cells has been imaged successfully by the application of IX-V, and the probe can effectively distinguish cancer cells from normal cells co-cultured in one dish by the difference of fluorescence intensity. In addition, the probe has been used for dual-modal imaging (NIRF and PA) of viscosity in tumor mice, which provides a tool for exploring the relationship between viscosity and diseases. That is to say, IX-V can achieve complementary imaging effects and has great application prospects in the tumor diagnosis.

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Cysteine is an important biological thiol and is closely related to cancer. It remains a challenge to develop a probe that can provide long-term fluorescence detection and imaging of Cys in cells as well as in living organisms. Here, a solid-state fluorophore HTPQ is combined with an acrylate group to construct a solid-state fluorescent probe HTPQC for Cys recognition. The fluorescence of the probe is quenched when the photoinduced electron transfer (PET) process is turned on and the excited-state intramolecular proton transfer (ESIPT) process is turned off. In the presence of Cys, an obvious solid-state fluorescence signal can be observed. The double quenching mechanism makes the probe HTPQC have the advantages of high sensitivity, good selectivity, and high contrast of biological imaging. Due to low cytotoxicity, the probe HTPQC can be used to detect exogenous and endogenous Cys in living cells and is capable of imaging over long periods of time. By making full use of long wavelengths, the probe can be applied for the detection of Cys levels in tumor mice and equipped with the ability to conduct long-term imaging in vivo.

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As cancer markers, hydrogen peroxide (H2 O2 ) and viscosity play an essential role in the development of tumors. Meanwhile, based on the performance of near-infrared (NIR) fluorescence imaging and the high efficiency of photodynamic therapy (PDT) and photothermal therapy (PTT) synergistic therapy, it is urgent to develop a dual-key (H2 O2 and viscosity) activated fluorescence probe for cancer phototherapy. Herein, a NIR-I/II fluorescence probe named BX-B is reported. In the presence of both H2 O2 and viscosity, the fluorescence signal of NIR-I (810 nm) and NIR-II (945 nm) can be released. In the presence of H2 O2 , the PDT and PTT effects are observed. BX-B is used to monitor its therapeutic effects in cancer cells and tumor-bearing mice due to the increased viscosity caused by PDT and PTT. In addition, the tumors of mice treated with BX-B are almost completely ablated after the laser irradiation based on its PDT and PTT synergistic therapy. This work provides a reliable platform for effective cancer treatment and immediate evaluation of therapeutic effects.

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Cysteine (Cys) is a crucial biological thiol that has a vital function in preserving redox homeostasis in organisms. Studies have shown that Cys is closely related to the development of cancer. Thus, it is necessary to design an efficient method to detect Cys for an effective cancer diagnosis. In this work, a novel tumor-targeting probe (Bio-Cy-S) for dual-modal (NIR fluorescence and photoacoustic) Cys detection is designed. The probe exhibits high selectivity and sensitivity toward Cys. After reaction with Cys, both NIR fluorescence and photoacoustic signals are activated. Bio-Cy-S has been applied for the dual-modal detection of Cys levels in living cells, and it can be used to distinguish normal cells from cancer cells by different Cys levels. In addition, the probe is capable of facilitating dual-modal imaging for monitoring changes in Cys levels in tumor-bearing mice. More importantly, the excellent tumor-targeting ability of the probe greatly improves the signal-to-noise ratio of imaging. To the best of our knowledge, this is the first Cys probe to combine targeting and dual-modal imaging performance for cancer diagnosis.

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A near-infrared fluorescent probe (IC-V) for detecting viscosity is constructed. The probe has a large Stokes shift (170 nm) and an about 180-fold increase in fluorescence intensity at 700 nm. In addition, IC-V can not only distinguish cancer cells from normal cells, but also monitor viscosity in normal mice and tumor-bearing mice.

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BACKGROUND: Whether the safety and efficacy of hepatic resection differ between patients whose hepatocellular carcinoma (HCC) is related to non-alcoholic fatty liver disease (NAFLD) or has other aetiologies is unknown. A systematic review was performed to explore potential differences between such conditions. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for relevant studies that reported hazard ratios (HRs) for overall and recurrence-free survival between patients with NAFLD-related HCC or HCC of other aetiologies. RESULTS: The meta-analysis involved 17 retrospective studies involving 2470 patients (21.5 per cent) with NAFLD-related HCC and 9007 (78.5 per cent) with HCC of other aetiologies. Patients with NAFLD-related HCC were older and had higher body mass index (BMI), but were less likely to have cirrhosis (50.4 per cent versus 64.0 per cent, P < 0.001). The two groups suffered similar rates of perioperative complications and mortality. Patients with NAFLD-related HCC had slightly higher overall survival (HR 0.87, 95 per cent c.i. 0.75 to 1.02) and recurrence-free survival (HR 0.93, 95 per cent c.i. 0.84 to 1.02) than those with HCC of other aetiologies. In the various subgroup analyses, the only significant finding was that Asian patients with NAFLD-related HCC had significantly better overall survival (HR 0.82, 95 per cent c.i. 0.71 to 0.95) and recurrence-free survival (HR 0.88, 95 per cent c.i. 0.79 to 0.98) than Asian patients with HCC of other aetiologies. CONCLUSION: The available evidence suggests that patients with NAFLD-related HCC have similar perioperative complications and mortality, but potentially longer overall and recurrence-free survival, compared with those with HCC of other aetiologies. Tailored surveillance strategies should be developed for patients with NAFLD without cirrhosis.

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Viscosity is an important component of cell microenvironment, and abnormal mitochondrial viscosity is associated with many diseases such as tumor and fatty liver. Herein, a near-infrared fluorescence probe (QX-V) based on quinoline-xanthene dye for detecting viscosity is constructed. In high viscosity medium, the free rotation of single bond is inhibited and the fluorescence is released. The probe shows high sensitivity together with good selectivity. Notably, QX-V has a long excitation wavelength (710 nm) and emission wavelength (786 nm). At the same time, the probe is a positively charged molecule that can target mitochondria. QX-V can not only distinguish cancer cells from normal cells, but also make a distinction between normal cells and fatty hepatocytes. In addition, QX-V is used to image viscosity abnormality in tumor-bearing mice. The probe also has a good ability to image viscosity abnormality caused by liver injury in fatty-liver mice.

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Objective:To explore the risk factors associated with liver metastasis in T 1 stage colorectal neoplasms patients and establish a prognostic model. Methods:Clinicopathological data of T 1 stage colorectal neoplasms patients from the Surveillance, Epidemiology, and End Results (SEER) database between January 1, 2004, and December 31, 2019 were included. The differences in clinicopathological characteristics between patients with and without liver metastasis were compared using Chi-square test, Wilcoxon rank-sum test, and multivariate Logistic regression analysis. Survival curves were plotted using Kaplan-Meier method, and the Log-Rank test was used to compare survival differences between the two groups. Univariate and multivariate analysis of prognostic factors were performed using the proportional Cox regression hazards regression model. Patients were randomly divided into training set and validation set at a ratio of 6∶4 using simple random sampling method. A nomogram model was established based on independent prognostic factors based on the results of the multivariate Cox regression analysis. The predictive ability of the model was evaluated using time-dependent receiver operating characteristic (ROC) curves and calibration curves. Results:A total of 28 258 T 1 stage colorectal neoplasms patients were included in the study. The multivariate Logistic regression analysis for liver metastasis occurrence indicated that the neuroendocrine neoplasms, elevated carcinoembryonic antigen (CEA) levels, larger neoplasms size, positive lymph node metastasis, and presence of cancer nodules were statistically significant differences ( P<0.05). For T 1 stage colorectal neoplasms patients with liver metastasis, the results of the multivariate Cox regression analysis showed that age, primary site, ethnicity, chemotherapy, and surgical treatment were independent prognostic factors ( P<0.05). The nomogram constructed based on these five prognostic factors had time-dependent ROC areas under the curve of 0.758, 0.797 and 0.729 for 1-year, 3-year, and 5-year survival rates, respectively, 0.749, 0.857, 0.871 in the validation set. The calibration curves of the nomogram in the training and validation sets were close to the 45-degree diagonal line. Conclusions:Neuroendocrine neoplasms, elevated CEA levels, larger neoplasms size, positive lymph node metastasis, and presence of cancer nodules are independent risk factors for liver metastasis in T 1 stage colorectal neoplasms. Age, primary site, ethnicity, chemotherapy, and surgical treatment are independent prognostic factors. The nomogram constructed based on these clinical characteristics has good discrimination and calibration abilities.

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The role of hydrogen sulphide (H2 S) in angiogenesis has been widely demonstrated. Vascular endothelial growth factor (VEGF) plays an important role in H2 S-induced angiogenesis. H2 S promotes angiogenesis by upregulating VEGF via pro-angiogenic signal transduction. The involved signalling pathways include the mitogen-activated protein kinase pathway, phosphoinositide-3 kinase pathway, nitric oxide (NO) synthase/NO pathway, signal transducer and activator of transcription 3 (STAT3) pathway, and adenosine triphosphate (ATP)-sensitive potassium (KATP ) channels. H2 S has been shown to contribute to tumour angiogenesis, diabetic wound healing, angiogenesis in cardiac and cerebral ischaemic tissues, and physiological angiogenesis during the menstrual cycle and pregnancy. Furthermore, H2 S can exert an anti-angiogenic effect by inactivating Wnt/ß-catenin signalling or blocking the STAT3 pathway in tumours. Therefore, H2 S plays a double-edged sword role in the process of angiogenesis. The regulation of H2 S production is a promising therapeutic approach for angiogenesis-associated diseases. Novel H2 S donors and/or inhibitors can be developed in the treatment of angiogenesis-dependent diseases.

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Dimesitylboryl-acceptor (A) and diarylamine-donor (D) substituents are introduced at α positions of BN-doped tetrathienonaphthalene in the same and opposite directions of the B-N bond, namely, B-BN-N and N-BN-B, in order to demonstrate how the substitution patterns influence the photophysical properties. The photophysical and electrochemical properties of these D-π-A molecules have been investigated in detail, aided by UV-vis absorption and fluorescence spectroscopy as well as cyclic voltammetry. We find that both B-BN-N and N-BN-B show the typical intramolecular charge transfer emission. N-BN-B exhibits strong fluorescence with a narrower band gap and stronger Lewis acidity than that of B-BN-N. DFT calculations help give a reasonable explanation that subtle differences in the electronic structure of the host skeleton could also influence the substituents and feed back this effect to the entire molecule.

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Panax ginseng (Panax ginseng C. A. Mey.) is a perennial herb of the genus ginseng, which is used as medicine with dried roots and rhizomes. With the deepening of research on ginseng, the chemical components and pharmacological effects of ginseng have gradually been discovered. Endophytes are beneficial to host plants. However, the composition of endophytes in different organs from ginseng is poorly elucidated. The report of ginsenoside production by endophytic microbes isolated from Panax sp., motivated us to explore the endophytic microbial diversity related to the roots, stems, and leaves. In this study, the V5-V7 variable region of endophytic bacteria 16S rRNA gene and V1 variable region of endophytic fungi ITS gene in different organs were analyzed by high-throughput sequencing. The diversity and abundance of endophytic microbes in the three organs are different and are affected by the organs. For example, the most abundant endophytic bacterial genus in roots was Mycobacterium, while, the stems and leaves were Ochrobactrum. Similarly, the fungal endophytes, Coniothyrium and Cladosporium, were also found in high abundance in stems, in comparison to roots and leaves. The Shannon index shows that the diversity of endophytic bacteria in roots is the highest, and the richness of endophytic bacterial was root > stem (p < 0.05). Principal coordinate analysis showed that there were obvious microbial differences among the three groups, and the endophytic bacterial composition of the leaves was closer to that of the roots. This study provides an important reference for the study of endophytic microorganisms in ginseng.

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Objective:To assess the efficacy and safety of the combination therapy of camrelizumab, apatinib, nab-paclitaxel, and S-1 for patients with locally unresectable advanced gastric cancer.Methods:From September 1, 2019 to August 1, 2021, in Beijing Friendship Hospital Affiliated to Capital Medical University, 17 patients with advanced gastric cancer were enrolled in this prospective, single-arm study. All the enrolled patients received camrelizumab, nab-paclitaxel, apatinib and S-1 combination therapy (in each 21 days cycle, camrelizumab 200 mg intravenously, D1; nab-paclitaxel 240 mg/m 2 intravenously, D2; apatinib 500 mg orally, once a day, D1-D21; S-1 40-60 mg twice a day, D1-D14). Patients who have been evaluated by multidisciplinary team to be eligible for radical surgery should stop treatment for at least 2 weeks. Patients were discontinued from the study when disease progression or unbearable toxicity, or withdrew consent. We analyzed the conversion rate, objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety.Statistical data were show by numbers and persentages(%), and comparisons between subgroups were assessed by Fisher′s exact probability method. Patients survival was analyzed using Kaplan-Meier curves and compared between groups using Log-rank. Results:At the data of cutoff (December 15, 2021), the median follow-up duration was 19.6 months. Eight of 17 patients underwent gastrectomy, and all of them were R0 resection (47.1%, 95% CI: 0.262-0.690). ORR was 47.1%, DCR was 82.4%, the median overall survival was 23.63 months. Grade 3 and 4 adverse events occurred in 3 patients (17.6%), including neutropenia, thrombocytopenia, anemia and upper gastrointestinal hemorrhage. There were no serious treatment-related adverse events or treatment-related deaths. Conclusion:In this trial, the combination of camrelizumab, apatinib, nab-paclitaxel and S-1 as the conversion therapy showed significant anti-tumor activity and manageable adverse events, providing a new option for locally unresectable advanced gastric cancer.