Metformin in elderly type 2 diabetes mellitus: dose-dependent dementia risk reduction.

This study aimed to investigate the controversial association between metformin use and diabetes-associated dementia in elderly patients with type 2 diabetes mellitus (T2DM) and evaluate the potential protective effects of metformin, as well as its intensity of use and dose-dependency, against dementia in this population. The study used a time-dependent Cox hazards model to evaluate the effect of metformin use on the incidence of dementia. The case group included elderly patients with T2DM (≥60 years old) who received metformin, while the control group consisted of elderly patients with T2DM who did not receive metformin during the follow-up period. Our analysis revealed a significant reduction in the risk of dementia among elderly individuals using metformin, with an adjusted hazard ratio of 0.34 (95% confidence interval: 0.33 to 0.36). Notably, metformin users with a daily intensity of 1 defined daily dose (DDD) or higher had a lower risk of dementia, with an adjusted hazard ratio (95% confidence interval) of 0.46 (0.22 to 0.6), compared to those with a daily intensity of <1 DDD. Additionally, the analysis of cumulative DDDs of metformin showed a dose-response relationship, with progressively lower adjusted hazard ratio across quartiles (0.15, 0.21, 0.28, and 0.53 for quartiles 4, 3, 2 and 1, respectively), compared to never metformin users (P for trend < 0.0001). Metformin use in elderly patients with T2DM is significantly associated with a substantial reduction in the risk of dementia. Notably, the protective effect of metformin demonstrates a dose-dependent relationship, with higher daily and cumulative dosages of metformin showing a greater risk reduction.

Early childhood general anesthesia and risk of Attention Deficit Hyperactivity Disorder.

BACKGROUND: The relationship between early childhood exposure to general anesthesia (GA) and the risk of developing Attention Deficit Hyperactivity Disorder (ADHD) is still uncertain and previous studies have presented conflicting results. This population-based cohort study aimed to investigate the potential relationship between GA exposure and ADHD risk using propensity score matching (PSM) in a large sample size. METHODS: The study included 15,072 children aged 0-3 years who received GA and were hospitalized for more than 1 day in Taiwan from 2004 to 2014. The nonexposed group was randomly selected through 1:1 PSM from the Taiwan Maternal and Child Health Database (TMCHD). The primary objectives of this study were to determine the incidence rates (IR) and incidence rate ratios (IRR) of ADHD in the two cohorts, employing Poisson regression models. RESULTS: The GA group and non-GA group each comprised 7,536 patients. The IR of ADHD was higher in the GA group (122.45 per 10,000 person-years) than in the non-GA group (64.15 per 10,000 person-years), and the IRR of ADHD in the GA group was 1.39 (95% CI: 1.26, 1.55). The study found that the number of times of exposure to GA, duration of exposure, male gender, and central nervous system surgery were significant risk factors for ADHD in the future. CONCLUSIONS: This study's findings suggest that there is a significant correlation between early childhood exposure to GA and the risk of developing ADHD, and GA may be an important risk factor for ADHD in children undergoing surgery. The study also identified several risk factors for ADHD, including the number of times of exposure to GA, duration of exposure, male gender, and central nervous system surgery.

Metformin monotherapy versus predominantly older non-metformin antidiabetic medications for cerebrovascular risk in early type 2 diabetes management.

AIM: Choosing the initial treatment for type 2 diabetes (T2D) is pivotal, requiring consideration of solid clinical evidence and patient characteristics. Despite metformin's historical preference, its efficacy in preventing cerebrovascular events lacked empirical validation. This study aimed to evaluate the associations between first-line monotherapy (metformin or non-metformin antidiabetic medications) and cerebrovascular complications in patients with T2D without diabetic complications. METHODS: We analysed 9090 patients with T2D without complications who were prescribed either metformin or non-metformin medications as initial therapy. Propensity score matching ensured group comparability. Cox regression analyses, stratified by initial metformin use, assessed cerebrovascular disease risk, adjusting for multiple covariates and using competing risk analysis. Metformin exposure was measured using cumulative defined daily doses. RESULTS: Metformin users had a significantly lower crude incidence of cerebrovascular diseases compared with non-users (p < .0001). Adjusted hazard ratios (aHRs) consistently showed an association between metformin use and a lower risk of overall cerebrovascular diseases (aHRs: 0.67-0.69) and severe events (aHRs: 0.67-0.69). The association with reduced risk of mild cerebrovascular diseases was significant across all models (aHRs: 0.73-0.74). Higher cumulative defined daily doses of metformin correlated with reduced cerebrovascular risk (incidence rate ratio: 0.62-0.94, p < .0001), indicating a dose-dependent effect. CONCLUSION: Metformin monotherapy is associated with a reduced risk of cerebrovascular diseases in early-stage T2D, highlighting its dose-dependent efficacy. However, the observed benefits might also be influenced by baseline differences and the increased risks associated with other medications, such as sulphonylureas. These findings emphasize the need for personalized diabetes management, particularly in mitigating cerebrovascular risk in early T2D stages.

Improved postoperative outcomes in pediatric major surgery: evidence from hospital volume analysis.

This study aimed to examine the association between hospital volume and postoperative outcomes in pediatric major surgery using a nationwide database. The study included pediatric patients who underwent first major elective inpatient surgery and hospitalization for more than 1 day. The results showed no significant difference in the risk of 30-day postoperative mortality based on hospital volume. However, patients in the middle- and high-volume groups had significantly lower rates of 30-day major complications, particularly deep wound infection. In terms of 90-day postoperative outcomes, patients in the high-volume group had a significantly lower risk of mortality and lower rates of major complications, particularly deep wound infection, pneumonia, and septicemia.  Conclusions: The study suggests that pediatric patients undergoing major surgery in high and middle-volume groups have better outcomes in terms of major complications compared to the low-volume group. What is Known: • Limited evidence exists on the connection between hospital volume and pediatric surgery outcomes. What is New: • A Taiwan-based study, using national data, found that high and middle hospital-volume groups experienced significantly lower rates of major complications within 30 and 90 days after surgery. • High-volume hospitals demonstrated a substantial decrease in the risk of 90-day postoperative mortality. • The study underscores the importance of specialized pediatric surgical centers and advocates for clear guidelines for hospital selection, potentially improving outcomes and informing future health policies.

Adverse postoperative outcomes in elderly patients with sarcopenia.

PURPOSE: No study has compared 30-day and 90-day adverse postoperative outcomes between old-age patients with and those without sarcopenia. PATIENTS AND METHODS: We categorize elderly patients receiving major surgery into two groups according to the presence or absence of preoperative sarcopenia that were matched at a 1:4 ratio through propensity score matching (PSM). We analyzed 30-day or 90-day adverse postoperative outcomes and mortality in patients with and without sarcopenia receiving major surgery. RESULTS: Multivariate logistic regression analyses revealed that the patients with preoperative sarcopenia were at significantly higher risk of 30-day postoperative mortality (adjusted odds ratio [aOR]. = 1.25; 95% confidence interval [CI]. = 1.03-1.52) and 30-day major complications such as postoperative pneumonia (aOR = 1.15; 95% CI = 1.00-1.40), postoperative bleeding (aOR = 2.18; 95% CI = 1.04-4.57), septicemia (aOR = 1.31; 95% CI = 1.03-1.66), and overall complications (aOR = 1.13; 95% CI = 1.00-1.46). In addition, surgical patients with sarcopenia were at significantly higher risk of 90-day postoperative mortality (aOR = 1.50; 95% CI = 1.29-1.74) and 90-day major complications such as pneumonia (aOR = 1.27; 95% CI = 1.10-1.47), postoperative bleeding (aOR = 1.90; 95% CI = 1.04-3.48), septicemia (aOR = 1.52; 95% CI = 1.28-1.82), and overall complications (aOR = 1.24; 95% CI = 1.08-1.42). CONCLUSIONS: Sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes such as pneumonia, postoperative bleeding, and septicemia and increases 30-day and 90-day postoperative mortality among patients receiving major surgery. No study has compared 30-day and 90-day adverse postoperative outcomes between patients with and those without sarcopenia. We conducted a propensity score?matched (PSM) population-based cohort study to investigate the adverse postoperative outcomes and mortality in patients undergoing major elective surgery with preoperative sarcopenia versus those without preoperative sarcopenia. We demonstrated that sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes, such as postoperative pneumonia, bleeding, septicemia, and mortality after major surgery. Therefore, surgeons and anesthesiologists should attempt to correct preoperative sarcopenia, swallowing function, and respiratory muscle training before elective surgery to reduce postoperative complications that contribute to the decrease in surgical mortality.

Novel insights into the classification of Shamblin III carotid body tumors from a neurosurgical perspective.

BACKGROUND AND PURPOSE: The classic Shamblin system fails to provide valuable guidance in many Shamblin's III carotid body tumors (III-CBTs) due to the variable forms of carotid arteries and the complex anatomic relationships in parapharyngeal space. We proposed a modified classification to separately divide III-CBTs into different subgroups on the basis of arterial relevant features and anatomical relevant features. MATERIALS AND METHODS: From 2020 to 2023, a total of 129 III-CBTs at a single institution were retrospectively analyzed. All cases were independently classified as arterial-relevant and anatomical-relevant subgroups. The pre-, peri- and postoperative data were summarized and compared accordingly. RESULTS: Among the 129 cases, 69 cases were identified as "Classical type", 23 cases as "Medial type", 27 cases as "Lateral type" and 10 cases as "Enveloped type" according to arterial morphologies. Besides, 76 cases were identified as "Common type", 15 cases as "Pharynx- invasion type", 18 cases as "Skull base-invasion type" and 20 cases as "Mixed type" according to anatomical relationships. "Enveloped type" of tumors in arterial-relevant classification and "Mixed type" of tumors in anatomical-relevant classification are the most challenging cases for surgeons with the lowest resection rate, highest incidence of carotid arteries injury and postoperative stroke. CONCLUSION: The modified classifications provide comprehensive understanding of different III-CBTs which are applicable for individualized treatment in clinical practice.

A new strategy for utilization of gasification ash: Manganese oxides-modified activated carbon for efficient copper citrate removal.

To address the challenges posed by solid waste generated from coal gasification ash, a pyrolysis self-activation method was employed to prepare activated carbon by gasification ash, followed by the modification with manganese oxide to enhance its adsorption performance. Subsequently, the removal efficiency and mechanism for copper citrate were investigated. The results demonstrated the successful preparation of manganese oxides modified gasification ash-derived activated carbon (GAC-MnOx), exhibiting a specific surface area of 158.3 m2/g and a pore volume of 0.1948 cm³/g. The kinetic process could be described by the pseudo-second-order kinetic model (R2 = 0.958). High removal efficiency and low concentration of dissolved Mn were observed within the pH range of 3-10, where the adsorption capacity of GAC-MnOx for copper citrate exhibited an inverse relationship with pH. Notably, the fitting results of the Langmuir model demonstrated that the maximum adsorption capacity of GAC-MnOx for copper citrate is determined to be 7.196 mg/g at pH 3. The adsorption capacity of GAC-MnOx was found to be significantly reduced to 0.26 mg/g as the pH decreased below 2, potentially attributed to the dissolution of Mn. The findings of the Dual-Mode model demonstrated that the copper citrate removal mechanism by GAC-MnOx involved both surface adsorption and precipitation processes as follows: the porous structure of activated carbon enables physical adsorption of copper citrate, the MnOx or oxygen-containing functional groups establish chemical bonds with copper citrate and subsequently precipitate onto the surface of the adsorbent. The physical adsorption remains predominant in the removal of copper citrate, despite a gradual decrease in its proportion with increasing pH and equilibrium concentrations. Moreover, the X-ray photoelectron spectroscopy results indicated that copper citrate might be oxidized by MnOx to release copper ions and be retained on the surface of the adsorbent, meaning the adsorption efficiency of Cu(II)-Cit by GAC was enhanced through MnOx oxidation. This study could provide a new strategy for the high-value resource utilization of gasification ash.

Hazel Leaf Polyphenol Extract Alleviated Cisplatin-Induced Acute Kidney Injury by Reducing Ferroptosis through Inhibiting Hippo Signaling.

Derived from hazelnuts, hazel leaf has been utilized in traditional folk medicine for centuries in countries such as Portugal, Sweden, and Iran. In our previous investigations, we conducted a preliminary assessment of the hazel leaf polyphenol extract (referred to as ZP) and identified nine compounds, such as kaempferol and chlorogenic acid, in its composition. ZP has shown promising properties as an antioxidant and anti-inflammatory agent. Our research has revealed that ZP has protective effects against cisplatin-induced acute kidney injury (AKI). We conducted a comprehensive examination of both the pathological and ultrastructural aspects and found that ZP effectively ameliorated renal tissue lesions and mitigated mitochondrial damage. Moreover, ZP significantly suppressed malondialdehyde levels while increasing glutathione and catalase concentrations in the kidneys of AKI-induced mice. ZP decreased the number of apoptotic cells and decreased pro-apoptotic protein expression in the kidneys of mice and human renal tubular epithelial cells (HK-2). Furthermore, treatment with ZP increased the levels of proteins marking anti-ferroptosis, such as GPX4, FTH1, and FSP1, in experiments both in vivo and in vitro. We elucidated the underlying mechanisms of ZP's actions, revealing its inhibitory effect on Yap phosphorylation and its regulation of Lats expression, which exert a protective influence on the kidneys. Furthermore, we found that inhibiting the Hippo pathway compromised ZP's nephroprotective effects in both in vitro and in vivo studies. In summary, this research shows that ZP exhibits renoprotective properties, effectively reducing oxidative damage, apoptosis, and ferroptosis in the kidneys by targeting the Hippo pathway.

Genomic-wide identification and expression analysis of R2R3-MYB transcription factors related to flavonol biosynthesis in Morinda officinalis.

BACKGROUND: The R2R3-MYB transcription factors are a crucial and extensive gene family in plants, which participate in diverse processes, including development, metabolism, defense, differentiation, and stress response. In the Lingnan region of China, Morinda officinalis is extensively grown and is renowned for its use as both a medicinal herb and food source. However, there are relatively few reports on the R2R3-MYB transcription factor family in M.officinalis. RESULTS: In this study, we identified 97 R2R3-MYB genes in the genome of Morinda officinalis and classified them into 32 subgroups based on phylogenetic comparison with Arabidopsis thaliana. The lack of recent whole-genome duplication events in M.officinalis may be the reason for the relatively few members of the R2R3-MYB family. We also further analyzed the physical and chemical characteristics, conserved motifs, gene structure, and chromosomal location. Gene duplication events found 21 fragment duplication pairs and five tandem duplication event R2R3-MYB genes in M.officinalis may also affect gene family expansion. Based on phylogenetic analysis, cis-element analysis, co-expression analysis and RT-qPCR, we concluded that MoMYB33 might modulate flavonol levels by regulating the expression of 4-coumarate-CoA ligase Mo4CL2, chalcone isomerase MoCHI3, and flavonol synthase MoFLS4/11/12. MoMYB33 and AtMYB111 showed the highest similarity of 79% and may be involved in flavonol synthase networks by the STRING database. Moreover, we also identified MoMYB genes that respond to methyl Jasmonate (MeJA) and abscisic acid (ABA) stress by RT-qPCR. CONCLUSIONS: This study offers a thorough comprehension of R2R3-MYB in M.officinalis, which lays the foundation for the regulation of flavonol synthesis and the response of MoMYB genes to phytohormones in M.officinalis.

Changes in sex hormones and their interactions are related to pain perception between different menstrual subphases.

Whether sex hormones are related to pain perception across the menstrual cycle is unclear. We examined changes in experimental pain perception in healthy young females between the early to midfollicular subphase (emF) and the midluteal subphase (mL) and explored the role of sex hormones. Sixty-six participants were involved in the study. We tested pressure pain, cold pain, ischemic pain, and needle pain, while at the same time we measured sex hormones levels in two menstrual subphases. Only the right ulna pressure test showed a significant reduction in pain threshold (PPTh3) during the mL. The absolute change of PPTh3 (PPTh3mL - PPTh3emF) was related to the absolute change of prolactin. The relative change of the range of pain tolerance for pressure pain of the right ulna (RPT3rc) was related to the relative change of progesterone (Prc) and estradiol (E2rc) levels, and the interaction effects showed that at Prc ≤ 30, E2rc was positively correlated with RPT3rc. The same, the relative change of pressure pain tolerance of the pulp of the middle finger on the right hand (PPTo4rc) was related to E2rc and Prc, and the results of the interaction between E2rc and Prc suggest that when E2rc is ≤0.8, Prc is positively correlated with PPTo4rc. Two different formulas were applied in this study and showed inconsistent results. Most pain tests showed no difference between the two subphases of the menstrual cycle. Only the relative changes of the PPTo4 and RPT3 are related to the E2rc and Prc, respectively, between menstrual subphases in an interactive way in healthy young women.

Intelligent water perimeter security event recognition based on NAM-MAE and distributed optic fiber acoustic sensing system.

Distributed optical acoustic sensing (DAS) based on phase-sensitive optical time-domain reflectometry can realize the distributed monitoring of multi-point disturbances along an optical fiber, thus making it suitable for water perimeter security applications. However, owing to the complex environment and the production of various noises by the system, continuous and effective recognition of disturbance signals becomes difficult. In this study, we propose a Noise Adaptive Mask-Masked Autoencoders (NAM-MAE) algorithm based on the novel mask mode of a Masked Autoencoders (MAE) and applies it to the intelligent event recognition in DAS. In this method, fewer but more accurate features are fed into the deep learning model for recognition by directly shielding the noise. Taking the fading noise generated by the system as an example, data on water perimeter security events collected in DAS underwater acoustic experiments are used. The NAM-MAE is compared with other models. The results indicate higher training accuracy and higher convergence speed of NAM-MAE than other models. Further, the final test accuracy reaches 96.6134%. It can be demonstrated that the proposed method has feasibility and superiority.

Ultramicro and ultrasensitive detection of lipopolysaccharides based on triple-signal amplification via ultrafast ATRP and an ultramicroelectrode.

Highly sensitive testing of trace lipopolysaccharides (LPS) is very important due to their high toxicity to the human body. Here, an ultrasensitive electrochemical sensor requiring only 5 µL solution was developed for LPS detection via triple-signal amplification based on ultrafast atom transfer radical polymerization (UATRP) and a Au ultramicroelectrode (UME). Firstly, the Au UME was modified with gold nanoparticles (nAu) and an LPS aptamer (Apt) in turn. When the Apt recognized LPS, the ATRP initiator of 4-(bromomethyl)phenylboronic acid (BPA) could be tethered to the electrode by covalent cross-linking between the phenylboronic acid moiety and the cis-diol site of LPS. Then UATRP was conducted for 2.5 min with nitrogen-doped carbon quantum dots (N-CQDs) as the photocatalyst and methylacrolein (MLA) as the monomer. After the electroactive probes of Ag nanoparticles (AgNPs) were formed on the surface of poly(MLA) by the silver mirror reaction, the electrochemical sensor was successfully prepared. Under the optimal conditions, the sensor exhibited a lower detection limit and a wider linear range when it was compared with a similar assay for LPS. In particular, the LOD of 7.99 × 10-2 pg mL-1 was better than that of the limulus amoebocyte lysate (LAL)-based technique, which is the gold standard for LPS detection. In the end, the sensor reported in this paper showed good selectivity and satisfactory feasibility for LPS detection in real biological samples and food products. The results obtained from the drug, blood and potable water samples laid a strong foundation for its clinical applications and application in other fields.

An ultrasensitive electrochemical sensor for phospholipase C via signal amplification based on breathing ATRP and its application.

Phospholipase C (PLC) has important biological functions in specific cancer types, immune disorders and neurodegeneration. Here, an ultrasensitive electrochemical sensor for PLC was developed via signal amplification based on breathing atom transfer radical polymerization (ATRP). First, phosphatidylethanolamine (PE) was immobilized on the surface of a gold electrode by L-cysteine and cross-linker. Then, PE was specially hydrolyzed by PLC to obtain the phosphate groups and tethered with the ATRP initiator α-bromophenacetic acid (BPAA) by the coordination action of Zr4+. After the breathing ATRP, a large number of electroactive monomers (ferrocenylmethyl methacrylate, FcMMA) were successfully grafted from BPAA. The experimental results indicated that the detection signal of the obtained electrode (sensor) was proportional to the concentration of PLC. The sensor showed a low detection limit of 0.270 U L-1 and a wide linear range of 1-40 U L-1 (R2 = 0.997). Most importantly, the sensor was successfully applied to detect PLC in breast cancer cells (MCF-7, MDA-MB-231) and nontumor cells (MCF-10A). The value obtained by our electrochemical sensor had no obvious difference from that determined by the commercial ELISA kit. These results showed that the fabricated PLC sensor had acceptable potential in clinical applications.

Dementia risk amongst older adults with hip fracture receiving general anaesthesia or regional anaesthesia: a propensity-score-matched population-based cohort study.

BACKGROUND: Preclinical studies have indicated that anaesthesia is an independent risk factor for dementia, but the clinical associations between dementia and different types of general anaesthesia or regional anaesthesia remain unclear. We conducted a population-based cohort study using propensity-score matching to compare dementia incidence in patients included in the Taiwanese National Health Insurance Research Database who received various anaesthetic types for hip fracture surgery. METHODS: Patients aged ≥65 yr who received elective hip fracture surgery from 2002 to 2019 were divided into three groups receiving either inhalational anaesthesia (GA), total intravenous anaesthesia-general anaesthesia (TIVA-GA), or regional anaesthesia (RA), and matched in a 1:1 ratio. The incidence rates of dementia were then determined. RESULTS: Propensity-score matching yielded 89 338 patients in each group (N=268 014). Dementia incidence rates in the inhalational GA, TIVA-GA, and RA groups were 4821, 3400, and 2692 per 100 000 person-years, respectively. The dementia incidence rate ratio (95% confidence interval [CI]) for inhalational GA to TIVA-GA was 1.19 (1.14-1.25), for inhalational GA to RA was 1.51 (1.15-1.66), and for TIVA-GA to RA was 1.28 (1.09-1.51). CONCLUSIONS: The incidence rate ratios of dementia amongst older adults undergoing hip fracture surgery were higher for those receiving general anaesthesia than for those receiving regional anaesthesia, with inhalational anaesthesia associated with a higher incidence rate ratio for dementia than total intravenous anaesthesia (TIVA).

Preventive and therapeutic effects of natural products and herbal extracts on nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is a common condition that is prevalent in patients who consume little or no alcohol, and is characterized by excessive fat accumulation in the liver. The disease is becoming increasingly common with the rapid economic development of countries. Long-term accumulation of excess fat can lead to NAFLD, which represents a global health problem with no effective therapeutic approach. NAFLD is a complex, multifaceted pathological process that has been the subject of extensive research over the past few decades. Herbal medicines have gained attention as potential therapeutic agents to prevent and treat NAFLD due to their high efficacy and low risk of side effects. Our overview is based on a PubMed and Web of Science database search as of Dec 22 with the keywords: NAFLD/NASH Natural products and NAFLD/NASH Herbal extract. In this review, we evaluate the use of herbal medicines in the treatment of NAFLD. These natural resources have the potential to inform innovative drug research and the development of treatments for NAFLD in the future.

Anti-Colorectal Cancer Activity of Solasonin from Solanum nigrum L. via Histone Deacetylases-Mediated p53 Acetylation Pathway.

(1) Background: Solanum nigrum L. is a plant of the genus Solanum in the family Solanaceae and is commonly used to treat tumors. Solasonin (SS) is a steroidal alkaloid extracted from Solanum nigrum L. that has anti-colorectal cancer (CRC) activity. (2) Methods: Column chromatography, semi-preparative HPLC and cellular activity screening were used to isolate potential anti-CRC active compounds in Solanum nigrum L., and structure identification using 1H-NMR and 13C-NMR techniques. Expression levels of HDAC in CRC were mined in the UALCAN database. The in vitro effects of SS on SW620 cell line and its mechanism were examined via Western blot, EdU staining, flow cytometry and immunofluorescence. CRC xenograft model and IHC staining were mainly used to evaluate the role of SS in vivo. (3) Results: The results showed that SS was the most potent anti-CRC component in Solanum nigrum L., which induced apoptosis and cell cycle arrest in the SW620 cell line. HDAC was highly expressed in CRC. The treatment of SW620 cell line with SS resulted in a significant downregulation of HDAC, an increase in the level of P53 acetylation and a subsequent increase in the level of P21. The in vivo validation results showed that SS could effectively inhibit CRC growth, which was associated with the downregulation of HDAC. (4) Conclusions: SS treatment for CRC mainly works through the induction of apoptosis and cycle arrest, and its mechanism of action is mainly related to HDAC-induced P53 acetylation, and the HDAC/P53 signaling pathway may be a potential pathway for the treatment of CRC.

Chronic pain following elective surgery under general anesthesia in older adults.

BACKGROUND: The purpose of this study was to investigate the association between age and chronic postsurgical pain (CPSP) in patients who underwent elective surgery under general anesthesia, with a focus on long-term postsurgical analgesic use. To our knowledge, no previous study has examined this relationship in detail between older and younger patients. METHODS: We conducted a propensity score-matched (PSM) study to compare the rates of long-term (3 or 6 months) postoperative analgesic use between older adult (≥ 65 years) and younger (< 65 years) patients. Multivariate logistic regression was used to assess the use of analgesics as a surrogate indicator of CPSP. RESULTS: The PSM analysis included 62,784 surgical patients (31,392 in each group). Three months after surgery, the rates of analgesic use were significantly higher in the older age group (adjusted odds ratio [aOR], 1.45; 95% confidence interval [CI], 1.41-1.49) as well as for opioid use specifically (aOR, 1.34; 95% CI, 1.29-1.39). Six months after surgery, the rates of analgesic use remained higher in the older age group (aOR, 1.52; 95% CI, 1.47-1.58), and similarly for opioid use specifically (aOR, 1.42; 95% CI, 1.36-1.48). CONCLUSIONS: Our findings suggest that older adults have higher rates of long-term analgesic use for CPSP after elective surgery under general anesthesia. This study highlights the importance of addressing CPSP in older adult patients and considering age-related factors when managing postoperative pain.

The positive feedback loop of NHE1-ERK phosphorylation mediated by BRAFV600E mutation contributes to tumorigenesis and development of glioblastoma.

The v-raf murine sarcoma viral oncogene homolog B1 (BRAF) activating mutation V600E (BRAFV600E) is involved in glioblastoma multiforme (GBM). Na/H exchanger 1 (NHE1), a main pH regulator affecting cell microenvironment, is hyper-expressed in GBM. However, the relationship between BRAFV600E signal pathway and NHE1 in GMB cells remains unclear. This study found that NHE1 was a downstream target of BRAFV600E and an upstream factor of extracellular signal-regulated kinase (ERK). In addition, there was a positive feedback loop between NHE1-ERK phosphorylation under regulation of BRAFV600E mutation contributing to the proliferation and invasion of GBM cells. Moreover, the proliferation and invasion abilities of BRAFV600E-mutant and BRAF wild type GBM cells were all suppressed by the NHE1 inhibitor, BRAFV600E inhibitor and combination of them. The inhibitory effect of combination of the two inhibitors was better than each single drug both in vitro and in vivo. Combination of BRAFV600E and NHE1 inhibitors could be considered as a new therapeutic regimen for GBM, especially for GBM with BRAFV600E.

Association between long-term opioid use and cancer risk in patients with chronic pain: a propensity score-matched cohort study.

BACKGROUND: Whether long-term opioid use is an independent risk factor for cancer progression remains unclear. Therefore, we conducted a propensity score-matched population-based cohort study to compare cancer incidence between patients with chronic pain with and without opioid use. METHODS: Data from January 2008 to December 2019 were obtained from the Taiwan National Health Insurance Research Database. Patients were categorised into two groups according to the presence or absence of opioid use, and matched at a 4:1 ratio. The incidence rate ratios for specific cancers were determined. RESULTS: Propensity score-matching yielded 63 610 patients: 50 888 with opioid use (the opioid group) and 12 722 without (the non-opioid group). In a multivariate Cox regression analysis, the adjusted hazard ratio (95% confidence interval) for cancers in the opioid group compared with the non-opioid group was 2.66 (1.44-2.94; P<0.001). The incidence rate ratios (95% confidence interval) for lung, hepatocellular, colorectal, breast, prostate, head and neck, pancreatic, gastric, oesophageal, and ovarian cancers for the opioid group were 1.87 (1.41-2.43), 1.97 (1.56-2.50), 2.39 (1.87-3.03), 2.43 (1.75-3.33), 2.00 (1.35-3.03), 1.79 (1.14-2.86), 1.87 (1.13-2.12), 2.43 (1.52-3.85), 1.82 (0.92-3.70), and 2.33 (1.01-5.55), respectively. CONCLUSION: There was an association between long-term opioid use and development of cancer in patients with chronic pain, which should be confirmed in future studies.

Effect of opioids on cancer survival in patients with chronic pain: a propensity score-matched population-based cohort study.

BACKGROUND: The impact of opioid analgesic use before cancer diagnosis on survival in patients with chronic pain is unclear. Therefore, we designed a propensity score-matched population-based cohort study to compare overall and cancer-related survival of patients with chronic pain who received long-term opioid analgesic treatment with that of those who did not receive such treatment. METHODS: We included patients with chronic pain and categorised them into the following two groups according to their analgesic use: patients with cancer and chronic pain who were prescribed ≥180 defined daily doses of opioid analgesics per year >3 months before cancer diagnosis comprised the case group, and those who were prescribed <28 defined daily doses of opioid analgesics per year before cancer diagnosis comprised the control group. Patients in both groups were matched at a ratio of 1:5. The primary outcome was overall long-term survival. RESULTS: The matching process yielded a final cohort of 1716 patients (286 and 1430 in the case and control groups, respectively) who were eligible for further analysis. The adjusted hazard ratio for overall survival in patients receiving long-term opioids was 3.53 (95% confidence interval: 3.03-4.11; P<0.001). CONCLUSIONS: Long-term opioid analgesic use before cancer diagnosis might be associated with poor overall survival in patients with chronic pain compared with such patients who did not receive long-term opioid analgesics.