Perioperative chemotherapy improves survival of patients with locally advanced diffuse gastric cancer.

BACKGROUND: Whether patients with diffuse gastric cancer, which is insensitive to chemotherapy, can benefit from neoadjuvant or adjuvant chemotherapy has long been controversial. AIM: To investigate whether perioperative chemotherapy can improve survival of patients with locally advanced diffuse gastric cancer. METHODS: A total of 2684 patients with locally advanced diffuse gastric cancer from 18 population-based cancer registries in the United States were analyzed. RESULTS: Compared with surgery alone, perioperative chemotherapy improved the prognosis of patients with locally advanced gastric cancer. Before stabilized inverse probability of treatment weighting (IPTW), the median overall survival (OS) times were 40.0 months and 13.0 months (P < 0.001), respectively. After IPTW, the median OS times were 33.0 months and 17.0 months (P < 0.001), respectively. Neoadjuvant chemotherapy did not improve the prognosis of patients with locally advanced gastric cancer compared with adjuvant chemotherapy after IPTW. After IPTW, the median OS times were 38.0 months in the neoadjuvant chemotherapy group and 42.0 months in the adjuvant chemotherapy group (P = 0.472). CONCLUSION: Patients with diffuse gastric cancer can benefit from perioperative chemotherapy. There was no significant difference in survival between patients who received neoadjuvant chemotherapy and those who received adjuvant chemotherapy.

Reporting quality and risk of bias of randomized controlled trials of Chinese herbal medicine for multiple sclerosis.

Background: Multiple sclerosis (MS) is the most common non-traumatic disabling disease affecting young adults. A definitive curative treatment is currently unavailable. Many randomized controlled trials (RCTs) have reported the efficacy of Chinese herbal medicine (CHM) on MS. Because of the uncertain quality of these RCTs, the recommendations for routine use of CHM for MS remain inconclusive. The comprehensive evaluation of the quality of RCTs of CHM for MS is urgent. Methods: Nine databases, namely, PubMed, Embase, Web of Science, Cochrane Library, EBSCO, Sinomed, Wanfang Database, China National Knowledge Infrastructure, and VIP Database, were searched from inception to September 2023. RCTs comparing CHM with placebo or pharmacological interventions for MS were considered eligible. The Consolidated Standards of Reporting Trials (CONSORT) and its extension for CHM formulas (CONSORT-CHM Formulas) checklists were used to evaluate the reporting quality of RCTs. The risk of bias was assessed using the Cochrane Risk of Bias tool. The selection criteria of high-frequency herbs for MS were those with cumulative frequency over 50% among the top-ranked herbs. Results: A total of 25 RCTs were included. In the included RCTs, 33% of the CONSORT items and 21% of the CONSORT-CHM Formulas items were reported. Eligibility title, sample size calculation, allocation concealment, randomized implementation, and blinded description in CONSORT core items were reported by less than 5% of trials. For the CONSORT-CHM Formulas, the source and authentication method of each CHM ingredient was particularly poorly reported. Most studies classified the risk of bias as "unclear" due to insufficient information. The top five most frequently used herbs were, in order, Radix Rehmanniae Preparata, Radix Rehmanniae Recens, Herba Epimedii, Scorpio, and Poria. No serious adverse effect had been reported. Conclusions: The low reporting of CONSORT items and the unclear risk of bias indicate the inadequate quality of RCTs in terms of reporting completeness and result validity. The CONSORT-CHM Formulas appropriately consider the unique characteristics of CHM, including principles, formulas, and Chinese medicinal substances. To improve the quality of RCTs on CHM for MS, researchers should adhere more closely to CONSORT-CHM Formulas guidelines and ensure comprehensive disclosure of all study design elements.

Relative kinetic stability of defect patterns in two-dimensional nematic liquid crystals with rectangular confinement.

Guiding and dynamically modulating topological defects are critical challenges in defect engineering of liquid crystals. Here, we employ molecular dynamics simulations to investigate the transition dynamics and relative kinetic stability of defect patterns in two-dimensional nematic Gay-Berne liquid crystals confined within rectangular geometries. We observe the formation of various defect patterns including long-axis, diagonal, X-shaped, composite, and bend configurations under different confinement conditions. The competition between boundary effects and the uniformity of nematic orientation induces the continuous realignment of liquid crystal molecules, facilitating the spatially continuous transformation of defect patterns over time. This transition involves changes in both defect types and their locations, typically initiating from defect regions. Furthermore, we demonstrate that the relative stability of these defect patterns can be effectively controlled by adjusting confinement parameters and external field conditions. Our findings provide fundamental insights into the transition kinetics of defect patterns in confined nematic liquid crystals, thereby enhancing our ability to manipulate topological defects for advanced applications.

Pore Environmental Modification by Amino Groups in Robust Microporous MOFs for SF6 Capturing and SF6/N2 Separation.

Capturing and separating the greenhouse gas SF6 from nitrogen N2 have significant greenhouse mitigation potential and economic benefits. We used a pore engineering strategy to manipulate the pore environment of the metal-organic framework (MOF) by incorporating organic functional groups (-NH2). This resulted in an enhanced adsorption of SF6 and separation of the SF6/N2 mixture in the MOF. The introduction of amino (-NH2) groups into YTU-29 resulted in a reduction of the Brunauer-Emmett-Teller surface but an increase in interactions with SF6 within the confined pores. Water-stable YTU-29-NH2 showed a significantly higher SF6 uptake (95.5 cm3/g) than YTU-29 (77.4 cm3/g). The results of the breakthrough experiments show that YTU-29-NH2 has a significantly improved separation performance for SF6/N2 mixtures, with a high SF6 capture of 0.88 mmol/g compared to 0.56 mmol/g by YTU-29. This improvement is due to the suitable pore confinement and accessible -NH2 groups on pore surfaces. Considering its excellent regeneration ability and cycling performance, ultrastable YTU-29-NH2 demonstrates great potential for SF6 capturing and SF6/N2 separation.

Characterization of Gut Microbiota in Rats and Rhesus Monkeys After Methamphetamine Self-administration.

Methamphetamine (MA) is one of the most abused drugs globally, but the mechanism of its addiction remains unclear. Several animal studies have shown that the gut microbiota (GM) influences addictive behaviors, but the pattern of GM changes during addiction in animals of different species remains unclear. The aim of this study was to explore the association between dynamic changes in GM and MA self-administration acquisition among two classical mammals, rhesus monkeys (Macaca mulatta) and rats, MA self-administration models. Male Sprague-Dawley rats and male rhesus monkeys were subjected to classical MA self-administration training, and fecal samples were collected before and after MA self-administration training, respectively. 16S rRNA sequencing was used for GM analyses. We found that GM changes were more pronounced in rats than in rhesus monkeys, as evidenced by more GM taxa producing significant differences before and after MA self-administration training in rats than in monkeys. We also found that the expression of the genus Clostridia_vadinBB60_group significantly decreased after MA self-administration training in both rats and rhesus monkeys. Lactobacillus changes were significantly negatively correlated with total MA uptake in rats (Pearson R = - 0.666, p = 0.035; Spearman R = - 0.721, p = 0.023), whereas its change was also highly negatively correlated with total MA uptake in rhesus monkeys (Pearson R = - 0.882, p = 0.118; Spearman R = - 1.000, p = 0.083), although this was not significant. These findings suggest that MA causes significant alterations in GM in both rhesus monkeys and rats and that the genus Lactobacillus might be a common therapeutic target for MA uptake prevention across the species.

Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

CARD11-BCL10-MALT1 Complex-Dependent MALT1 Activation Facilitates Myocardial Oxidative Stress in Doxorubicin-Treated Mice via Enhancing k48-Linked Ubiquitination of Nrf2.

Aims: Downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) contributes to doxorubicin (DOX)-induced myocardial oxidative stress, and inhibition of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) increased Nrf2 protein level in rat heart suffering ischemia/reperfusion, indicating a connection between MALT1 and Nrf2. This study aims to explore the role of MALT1 in DOX-induced myocardial oxidative stress and the underlying mechanisms. Results: The mice received a single injection of DOX (15 mg/kg, i.p.) to induce myocardial oxidative stress, evidenced by increases in the levels of reactive oxidative species as well as decreases in the activities of antioxidative enzymes, concomitant with a downregulation of Nrf2; these phenomena were reversed by MALT1 inhibitor. Similar phenomena were observed in DOX-induced oxidative stress in cardiomyocytes. Mechanistically, knockdown or inhibition of MALT1 notably attenuated the interaction between Nrf2 and MALT1 and decreased the k48-linked ubiquitination of Nrf2. Furthermore, inhibition or knockdown of calcium/calmodulin-dependent protein kinase II (CaMKII-δ) reduced the phosphorylation of caspase recruitment domain-containing protein 11 (CARD11), subsequently disrupted the assembly of CARD11, B cell lymphoma 10 (BCL10), and MALT1 (CBM) complex, and reduced the MALT1-dependent k48-linked ubiquitination of Nrf2 in DOX-treated mice or cardiomyocytes. Innovation and Conclusion: The E3 ubiquitin ligase function of MALT1 accounts for the downregulation of Nrf2 and aggravation of myocardial oxidative stress in DOX-treated mice, and CaMKII-δ-dependent phosphorylation of CARD11 triggered the assembly of CBM complex and the subsequent activation of MALT1.

Preoperative prognostic nutritional index predicts long-term outcomes of patients with ampullary adenocarcinoma after curative pancreatoduodenectomy.

BACKGROUND: The prognostic nutritional index (PNI), a marker of immune-nutrition balance, has predictive value for the survival and prognosis of patients with various cancers. AIM: To explore the clinical significance of the preoperative PNI on the prognosis of ampullary adenocarcinoma (AC) patients who underwent curative pancreaticoduodenectomy. METHODS: The data concerning 233 patients diagnosed with ACs were extracted and analyzed at our institution from January 1998 to December 2020. All patients were categorized into low and high PNI groups based on the cutoff value determined by receiver operating characteristic curve analysis. We compared disease-free survival (DFS) and overall survival (OS) between these groups and assessed prognostic factors through univariate and multivariate analyses. RESULTS: The optimal cutoff value for the PNI was established at 45.3. Patients with a PNI ≥ 45.3 were categorized into the PNI-high group, while those with a PNI < 45.3 were assigned to the PNI-low group. Patients within the PNI-low group tended to be of advanced age and exhibited higher levels of aspartate transaminase and total bilirubin and a lower creatinine level than were those in the PNI-high group. The 5-year OS rates for patients with a PNI ≥ 45.3 and a PNI < 45.3 were 61.8% and 43.4%, respectively, while the 5-year DFS rates were 53.5% and 38.3%, respectively. Patients in the PNI- low group had shorter OS (P = 0.006) and DFS (P = 0.012). In addition, multivariate analysis revealed that the PNI, pathological T stage and pathological N stage were found to be independent prognostic factors for both OS and DFS. CONCLUSION: The PNI is a straightforward and valuable marker for predicting long-term survival after pancreatoduodenectomy. The PNI should be incorporated into the standard assessment of patients with AC.

C-Phycocyanin improves the quality of goat oocytes after in vitro maturation and vitrification.

In vitro maturation (IVM) and cryopreservation of goat oocytes are important for establishing a valuable genetic bank for domesticated female animals and improving livestock reproductive efficiency. C-Phycocyanin (PC) is a Spirulina extract with antioxidant, antiinflammatory, and radical scavenging properties. However, whether PC has positive effect on goat oocytes IVM or developmental competence after vitrification is still unknown. In this study, we found that first polar body extrusion (n = 293), cumulus expansion index (n = 269), and parthenogenetic blastocyst formation (n = 281) were facilitated by adding 30 µg/mL PC to the oocyte maturation medium when compared with the control groups and that supplemented with 3, 10, 100 or 300 µg/mL PC (P < 0.05). Although PC supplementation did not affect spindle formation or chromosome alignment (n = 115), it facilitated or improved cortical granules migration (n = 46, P < 0.05), mitochondria distribution (n = 39, P < 0.05), and mitochondrial membrane potential (n = 46, P < 10-4). Meanwhile, supplementation with 30 µg/mL PC in the maturation medium could significantly inhibit the reactive oxygen species accumulation (n = 65, P < 10-4), and cell apoptosis (n = 42, P < 0.05). In addition, PC increased the oocyte mRNA levels of GPX4 (P < 0.01), and decreased the mRNA and protein levels of BAX (P < 0.01). Next, we investigated the effect of PC supplementation in the vitrification solution on oocyte cryopreservation. When compared with the those equilibrate in the vitrification solution without PC, recovered oocytes in the 30 µg/mL PC group showed higher ratios of normal morphology (n = 85, P < 0.05), survival (n = 85, P < 0.05), first polar body extrusion (n = 62, P < 0.05), and parthenogenetic blastocyst formation (n = 107, P < 0.05). Meanwhile, PC supplementation of the vitrification solution increased oocyte mitochondrial membrane potential (n = 53, P < 0.05), decreased the reactive oxygen species accumulation (n = 73, P < 0.05), promoted mitochondria distribution (n = 58, P < 0.05), and inhibited apoptosis (n = 46, P < 10-3). Collectively, our findings suggest that PC improves goat oocyte IVM and vitrification by reducing oxidative stress and early apoptosis, which providing a novel strategy for livestock gamete preservation and utilization.

The CBM91 module enhances the activity of ß-xylosidase/α-L-arabinofuranosidase PphXyl43B from Paenibacillus physcomitrellae XB by adopting a unique loop conformation at the top of the active pocket.

Carbohydrate-binding module (CBM) family 91 is a novel module primarily associated with glycoside hydrolase (GH) family 43 enzymes. However, our current understanding of its function remains limited. PphXyl43B is a ß-xylosidase/α-L-arabinofuranosidase bifunctional enzyme from physcomitrellae patens XB belonging to the GH43_11 subfamily and containing CBM91 at its C terminus. To fully elucidate the contributions of the CBM91 module, the truncated proteins consisting only the GH43_11 catalytic module (rPphXyl43B-dCBM91) and only the CBM91 module (rCBM91) of PphXyl43B were constructed, respectively. The result showed that rPphXyl43B-dCBM91 completely lost hydrolysis activity against both p-nitrophenyl-ß-D-xylopyranoside and p-nitrophenyl-α-L-arabinofuranoside; it also exhibited significantly reduced activity towards xylobiose, xylotriose, oat spelt xylan and corncob xylan compared to the control. Thus, the CBM91 module is crucial for the ß-xylosidase/α-L-arabinofuranosidase activities in PphXyl43B. However, rCBM91 did not exhibit any binding capability towards corncob xylan. Structural analysis indicated that CBM91 of PphXyl43B might adopt a loop conformation (residues 496-511: ILSDDYVVQSYGGFFT) to actively contribute to the catalytic pocket formation rather than substrate binding capability. This study provides important insights into understanding the function of CBM91 and can be used as a reference for analyzing the action mechanism of GH43_11 enzymes and their application in biomass energy conversion.

Auto-suppression of Tet dioxygenases protects the mouse oocyte genome from oxidative demethylation.

DNA cytosine methylation plays a vital role in repressing retrotransposons, and such derepression is linked with developmental failure, tumorigenesis and aging. DNA methylation patterns are formed by precisely regulated actions of DNA methylation writers (DNA methyltransferases) and erasers (TET, ten-eleven translocation dioxygenases). However, the mechanisms underlying target-specific oxidation of 5mC by TET dioxygenases remain largely unexplored. Here we show that a large low-complexity domain (LCD), located in the catalytic part of Tet enzymes, negatively regulates the dioxygenase activity. Recombinant Tet3 lacking LCD is shown to be hyperactive in converting 5mC into oxidized species in vitro. Endogenous expression of the hyperactive Tet3 mutant in mouse oocytes results in genome-wide 5mC oxidation. Notably, the occurrence of aberrant 5mC oxidation correlates with a consequent loss of the repressive histone mark H3K9me3 at ERVK retrotransposons. The erosion of both 5mC and H3K9me3 causes ERVK derepression along with upregulation of their neighboring genes, potentially leading to the impairment of oocyte development. These findings suggest that Tet dioxygenases use an intrinsic auto-regulatory mechanism to tightly regulate their enzymatic activity, thus achieving spatiotemporal specificity of methylome reprogramming, and highlight the importance of methylome integrity for development.

Tracing the Change and Contribution of Subcutaneous Adipose to Skin Expansion Using a Luciferase-Transgenic Fat Transplantation Model.

BACKGROUND: During skin expansion, subcutaneous adipose tissue undergoes the greatest change. The adipose layer appears to gradually thin or even disappear in long-term expansion. The response and contribution of adipose tissue to skin expansion remain to be elucidated. METHODS: The authors established a novel expansion model by transplanting luciferase-transgenic adipose tissue into the rat dorsum, followed by integrated expansion, to trace the dynamic changes in subcutaneous adipose tissue during expansion and the migration of adipose tissue-derived cells. In vivo luminescent imaging was performed to continuously track the adipose tissue changes. Histologic analysis and immunohistochemical staining evaluated the regeneration and vascularization of the expanded skin. Growth factor expression in expanded skin with or without adipose tissue was determined to evaluate the paracrine effect of adipose tissue. Adipose tissue-derived cells were traced in vitro by anti-luciferase staining, and their fate was determined by costaining for PDGFRα, DLK1, and CD31. RESULTS: In vivo bioimaging showed that cells in adipose tissue were alive during expansion. After expansion, the adipose tissue exhibited fibrotic-like structures, with more DLK1 + preadipocytes. Skin expanded with adipose tissue was significantly thicker than that without adipose tissue, with more blood vessels and cell proliferation. Vascular endothelial growth factor, epidermal growth factor, and basic fibroblast growth factor expression was higher in adipose tissue than in skin, indicating paracrine support from adipose tissue. Luciferase-positive adipose tissue-derived cells were observed in expanded skin, indicating direct participation in skin regeneration. CONCLUSION: Adipose tissue transplantation can effectively promote long-term skin expansion by contributing to vascularization and cell proliferation by means of various mechanisms. CLINICAL RELEVANCE STATEMENT: The authors' findings suggest that it would be better if the expander pocket is dissected over the superficial fascia to preserve a layer of adipose tissue with skin. In addition, their findings support the treatment of fat grafting when expanded skin presents with thinning.

A preliminary study on the association of single nucleotide polymorphisms and methylation of dopamine system-related genes with psychotic symptoms in patients with methamphetamine use disorder.

Methamphetamine use disorder (MAUD) can substantially jeopardize public security due to its high-risk social psychology and behaviour. Given that the dopamine reward system is intimately correlated with MAUD, we investigated the association of single nucleotide polymorphisms (SNPs), as well as methylation status of dopamine receptor type 4 (DRD4), catechol-O-methyltransferase (COMT) genes, and paranoid and motor-impulsive symptoms in MAUD patients. A total of 189 MAUD patients participated in our study. Peripheral blood samples were used to detect 3 SNPs and 35 CpG units of methylation in the DRD4 gene promoter region and 5 SNPs and 39 CpG units in the COMT gene. MAUD patients with the DRD4 rs1800955 C allele have a lower percentage of paranoid symptoms than those with the rs1800955 TT allele. Individuals with paranoid symptoms exhibited a reduced methylation degree at a particular DRD4 CpG2.3 unit. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4CpG2.3 methylation degree were associated with a lower occurrence of paranoid symptoms. Meanwhile, those with the COMT rs4818 CC allele had lower motor-impulsivity scores in MAUD patients but greater COMT methylation levels in the promoter region and methylation degree at the COMT CpG 51.52 unit. Therefore, based only on the COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor-impulsive scores. Our preliminary results provide a clue that the combination of SNP genotype and methylation status of the DRD4 and COMT genes serve as biological indicators for the prevalence of relatively high-risk psychotic symptoms in MAUD patients.

Analysis of textbook outcomes for ampullary carcinoma patients following pancreaticoduodenectomy.

BACKGROUND: Textbook outcomes (TOs) have been used to assess the quality of surgical treatment for many digestive tumours but not ampullary carcinoma (AC). AIM: To discuss the factors associated with achieving a TO and further explore the prognostic value of a TO for AC patients undergoing curative pancreaticoduodenectomy (PD). METHODS: Patients who underwent PD at the China National Cancer Center between 1998 and 2020 were identified. A TO was defined by R0 resection, examination of ≥ 12 Lymph nodes, no prolonged hospitalization, no intensive care unit treatment, no postoperative complications, and no 30-day readmission or mortality. Cox regression analysis was used to identify the prognostic value of a TO for overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to identify predictors of a TO. The rate of a TO and of each indicator were compared in patients who underwent surgery before and after 2010. RESULTS: Ultimately, only 24.3% of 272 AC patients achieved a TO. A TO was independently associated with improved OS [hazard ratio (HR): 0.443, 95% confidence interval (95%CI): 0.276-0.711, P = 0.001] and RFS (HR: 0.379, 95%CI: 0.228-0.629, P < 0.001) in the Cox regression analysis. Factors independently associated with a TO included a year of surgery between 2010 and 2020 (OR: 4.549, 95%CI: 2.064-10.028, P < 0.001) and N1 stage disease (OR: 2.251, 95%CI: 1.023-4.954, P = 0.044). In addition, the TO rate was significantly higher in patients who underwent surgery after 2010 (P < 0.001) than in those who underwent surgery before 2010. CONCLUSION: Only approximately a quarter (24.3%) of AC patients achieved a TO following PD. A TO was independently related to favourable oncological outcomes in AC and should be considered as an outcome measure for the quality of surgery. Further multicentre research is warranted to better elucidate its impact.

Novel prognostic score based on the preoperative total bilirubin-albumin ratio and fibrinogen-albumin ratio in ampullary adenocarcinoma.

BACKGROUND: The preoperative total bilirubin-albumin ratio (TBAR) and fibrinogen-albumin ratio (FAR) have been proven to be valuable prognostic factors in various cancers. AIM: To detect the prognostic value of TBAR and FAR in ampullary adenocarcinoma (AC) patients who underwent curative pancreaticoduodenectomy. METHODS: AC patients who underwent curative pancreaticoduodenectomy in the National Cancer Center of China between 1998 and 2020 were retrospectively reviewed. The prognostic cutoff values of TBAR and FAR were determined through the best survival separation model. Then, a novel prognostic score combining TBAR and FAR was calculated and validated through the logistic regression analysis and Cox regression analysis. RESULTS: A total of 188 AC patients were enrolled in the current study. The best cutoff values of TBAR and FAR for predicting overall survival were 1.7943 and 0.1329, respectively. AC patients were divided into a TBAR-low group (score = 0) vs a TBAR-high group (score = 1) and a FAR-low group (score = 0) vs a FAR-high group (score = 1). The total score was calculated as a novel prognostic factor. Multivariable logistic regression analysis revealed that a high score was an independent protective factor for recurrence [score = 1 vs score = 0: Odds ratio (OR) = 0.517, P = 0.046; score = 2 vs score = 0 OR = 0.236, P = 0.038]. In addition, multivariable survival analysis also demonstrated that a high score was an independent protective factor in AC patients (score = 2 vs score = 0: Hazard ratio = 0.230, P = 0.046). CONCLUSION: A novel prognostic score based on preoperative TBAR and FAR has been demonstrated to have good predictive power in AC patients who underwent curative pancreaticoduodenectomy. However, more studies with larger samples are needed to validate this conclusion.

The interaction between alpha-synuclein and mitochondrial dysfunction in Parkinson's disease.

Parkinson's disease (PD) is an aging-associated neurodegenerative disorder with the hallmark of abnormal aggregates of alpha-synuclein (α-syn) in Lewy bodies (LBs) and Lewy neurites (LNs). Currently, pathogenic α-syn and mitochondrial dysfunction have been considered as prominent roles that give impetus to the PD onset. This review describes the α-syn pathology and mitochondrial alterations in PD, and focuses on how α-syn interacts with multiple aspects of mitochondrial homeostasis in the pathogenesis of PD.

A prospective study of the association between serum klotho and mortality among adults with rheumatoid arthritis in the USA.

BACKGROUND: While it is known that klotho has negative regulatory effects in a variety of diseases such as metabolic disorders and kidney disease, the specific role of klotho in rheumatoid arthritis (RA) and its effect on mortality are unclear. This study investigated the association between serum klotho levels and mortality in patients with RA. METHODS: This study included 841 adults with RA from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016 to extract the concentrations of serum klotho. The association between klotho and RA was determined using Cox regression, Kaplan-Meier (KM) curves, and restricted cubic spline (RCS) models. RESULTS: A total of 841 patients with RA were included in this study, who were divided into four groups based on the quartiles of serum klotho levels (Q1, Q2, Q3, and Q4). Cox regression analysis with adjustment for covariates revealed that high levels of klotho lowered the risk of both all-cause and cardiovascular mortality compared to the Q1 group. The KM curve analysis suggested that this effect was more pronounced for all-cause mortality. The RCS-fitted Cox regression model indicated a U-shaped correlation between serum klotho levels and RA mortality. The risk of all-cause mortality increased with decreasing serum klotho levels below a threshold of 838.81 pg/mL. Subgroup analysis revealed that the protective effect of klotho was more pronounced in patients with the following characteristics: male, white ethnicity, age ≥ 60 years, body mass index < 25 kg/m2, estimated glomerular filtration rate ≥ 60 mL/ (min × 1.73 m2), and 25-hydroxyvitamin D level ≥ 50 nmol/L. CONCLUSION: Serum klotho levels had a U-shaped correlation with all-cause mortality in patients with RA, indicating that maintain a certain level of serum klotho could prevent premature death.

Analysis of Adverse Drug Reaction Reports from a Public Hospital in Shanxi Province in 2022.

Objective: Through analyzing the characteristics and influencing factors of adverse drug reactions/adverse events (ADR/ADE) in a hospital to promote rational drug use in the clinic. Methods: A total of 1221 ADR/ADE reports collected from a hospital in 2022 were retrieved through the National Adverse Drug Reaction Monitoring Center. The effective reports were screened according to the Guiding Principles for Collection and Reporting of Individual Adverse Drug Reactions, and classified the standardized drugs. The systems/organs and main clinical symptoms affected by ADR/ADE were classified according to the WHO Glossary of Adverse Drug Reaction Terms. The severity, age and gender, occupational distribution, drug category, route of administration, drug dosage form, system/organ involved, and main clinical symptoms of ADR/ADE reports were analyzed. Results: Among 1221 ADR/ADE reports, 890 cases (75.27%) reported by doctors; 144 cases (11.79%) were serious; Precisely 49.22% of ADR/ADE occurred in patients aged 51 to 70 years old; The highest incidence of adverse reactions was 636 cases (52.09%) by intravenous infusion, 406 cases (33.25%) by oral administration. The top categories of reported cases were anti-infective drugs (29.40%) and anti-tumor drugs (27.52%); Systems/organs involved in ADR/ADE were mainly the skin and its accessories (24.96%) and blood system (21.35%). 166 cases were cured, 893 cases were symptomatic, 160 cases were unknown, and 2 cases had sequelae. Conclusion: The occurrence of ADR/ADE is related to many influencing factors such as age, drug categories, and route of administration. Therefore, it is recommended that hospitals strengthen the monitoring of ADR/ADE, especially the elderly, anti-infective drugs and intravenous administration.

Impact of perioperative blood transfusion on oncological outcomes in ampullary carcinoma patients underwent pancreaticoduodenectomy.

BACKGROUND: The effect of perioperative blood transfusion (PBT) on the prognosis of ampullary carcinoma (AC) is still debated. AIM: To explore the impact of PBT on short-term safety and long-term survival in AC patients who underwent pancreaticoduodenectomy. METHODS: A total of 257 patients with AC who underwent pancreaticoduodenectomy between 1998 and 2020 in the Cancer Hospital, Chinese Academy of Medical Sciences, were retrospectively analyzed. We used Cox proportional hazard regression to identify prognostic factors of overall survival (OS) and recurrence-free survival (RFS) and the Kaplan-Meier method to analyze survival information. RESULTS: A total of 144 (56%) of 257 patients received PBT. The PBT group and nonperioperative blood transfusion group showed no significant differences in demographics. Patients who received transfusion had a comparable incidence of postoperative complications with patients who did not. Univariable and multivariable Cox proportional hazard regression analyses indicated that transfusion was not an independent predictor of OS or RFS. We performed Kaplan-Meier analysis according to subgroups of T stage, and subgroup analysis indicated that PBT might be associated with worse OS (P < 0.05) but not RFS in AC of stage T1. CONCLUSION: We found that PBT might be associated with decreased OS in early AC, but more validation is needed. The reasonable use of transfusion might be helpful to improve OS.