Cat owners do not provide more reliable weight estimates for cats compared with veterinary professionals in an emergency setting.

OBJECTIVES: The aim of the present study was to assess the accuracy of weight estimation in cats provided by pet owners, veterinary technicians, house officers (interns and residents) and attending clinicians in an emergency room (ER). An additional objective was to determine whether carrying the cat contributed to a more accurate weight estimate. METHODS: A total of 72 cats presented to an ER and were enrolled in the study. Pet owners, veterinary technicians, house officers and attending clinicians were asked to record the cats' estimated weights on individual data collection cards. The actual weights of the cats were then obtained and compared with participants' estimations. RESULTS: There were no significant differences between weight estimates provided by pet owners, veterinary technicians, house officers and attending clinicians. Similarly, neither the length of experience of the veterinary staff nor carrying the cat had an effect on the provision of a more accurate weight estimate. CONCLUSIONS AND RELEVANCE: Pet owners are no better at weight estimation of cats in the ER setting compared with veterinary professionals. Carrying the cat did not improve the accuracy of weight estimation among veterinary professionals. The mean cat weight of 4.9 kg could be used as an average cat weight in an emergency situation for an adult cat.

A novel fast hybrid capture sequencing method for high-efficiency common human coronavirus whole-genome acquisition.

Rapid and accurate sequencing of the entire viral genome, coupled with continuous monitoring of genetic changes, is crucial for understanding the epidemiology of coronaviruses. We designed a novel method called micro target hybrid capture system (MT-Capture) to enable whole-genome sequencing in a timely manner. The novel design of probes used in target binding exhibits a unique and synergistic "hand-in-hand" conjugation effect. The entire hybrid capture process is within 2.5 hours, overcoming the time-consuming and complex operation characteristics of the traditional liquid-phase hybrid capture (T-Capture) system. By designing specific probes for these coronaviruses, MT-Capture effectively enriched isolated strains and 112 clinical samples of coronaviruses with cycle threshold values below 37. Compared to multiplex PCR sequencing, it does not require frequent primer updates and has higher compatibility. MT-Capture is highly sensitive and capable of tracking variants.IMPORTANCEMT-Capture is meticulously designed to enable the efficient acquisition of the target genome of the common human coronavirus. Coronavirus is a kind of virus that people are generally susceptible to and is epidemic and infectious, and it is the virus with the longest genome among known RNA viruses. Therefore, common human coronavirus samples are selected to evaluate the accuracy and sensitivity of MT-Capture. This method utilizes innovative probe designs optimized through probe conjugation techniques, greatly shortening the time and simplifying the handwork compared with traditional hybridization capture processes. Our results demonstrate that MT-Capture surpasses multiplex PCR in terms of sensitivity, exhibiting a thousandfold increase. Moreover, MT-Capture excels in the identification of mutation sites. This method not only is used to target the coronaviruses but also may be used to diagnose other diseases, including various infectious diseases, genetic diseases, or tumors.

PRMT5-mediated homologous recombination repair is essential to maintain genomic integrity of neural progenitor cells.

Maintaining genomic stability is a prerequisite for proliferating NPCs to ensure genetic fidelity. Though histone arginine methylation has been shown to play important roles in safeguarding genomic stability, the underlying mechanism during brain development is not fully understood. Protein arginine N-methyltransferase 5 (PRMT5) is a type II protein arginine methyltransferase that plays a role in transcriptional regulation. Here, we identify PRMT5 as a key regulator of DNA repair in response to double-strand breaks (DSBs) during NPC proliferation. Prmt5F/F; Emx1-Cre (cKO-Emx1) mice show a distinctive microcephaly phenotype, with partial loss of the dorsal medial cerebral cortex and complete loss of the corpus callosum and hippocampus. This phenotype is resulted from DSBs accumulation in the medial dorsal cortex followed by cell apoptosis. Both RNA sequencing and in vitro DNA repair analyses reveal that PRMT5 is required for DNA homologous recombination (HR) repair. PRMT5 specifically catalyzes H3R2me2s in proliferating NPCs in the developing mouse brain to enhance HR-related gene expression during DNA repair. Finally, overexpression of BRCA1 significantly rescues DSBs accumulation and cell apoptosis in PRMT5-deficient NSCs. Taken together, our results show that PRMT5 maintains genomic stability by regulating histone arginine methylation in proliferating NPCs.

CLINICAL AND HISTOPATHOLOGIC OCULAR FINDINGS IN AQUARIUM-HOUSED COWNOSE RAYS (RHINOPTERA BONASUS).

Cownose rays (Rhinoptera bonasus) are susceptible to ocular disease with their prominent globes, but despite being popular animals housed in aquaria, there is little published information about their normal ocular anatomy and common pathologic ocular findings. A total of 63 live cownose rays (CNR) from three unrelated, separately housed groups had ocular examinations, and 5 adult rays were selected for ocular ultrasound. All examinations were performed out of the water, and most without anesthesia. Clinical findings were described, categorized, and scored by severity. Sixty-two of 63 rays (123 eyes) had clinical abnormalities, including 110 eyes with corneal pathology (mild = 76, moderate/severe = 34) and 74 eyes with intraocular pathology (mild = 44, moderate/severe = 30). Grey-to-white corneal opacities were the most common pathology (n = 58 rays/100 eyes) followed by cataracts (n = 41 rays/58 eyes), then persistent (or dysplastic) pupillary membranes (n = 14 rays/15 eyes). Most pathologic findings appeared inactive, but one aquarium had several CNR with active ocular pathology. There was a significant association between the diagnosis of moderate/severe corneal and intraocular pathology with age (P = 0.008 and P = 0.014, respectively) and weight (P = 0.001 and P = 0.039, respectively), as well as moderate/severe corneal pathology and group sampled (P = 0.03). There were no other significant variables identified. Additionally, histopathology of 14 eyes (11 rays) from two different facilities were examined, with keratitis (n = 8) and uveitis (n = 2) as the most common lesions. This study shows a high prevalence of pathologic ocular findings in cownose ray eyes with heavier adults more likely to be affected than lighter juveniles. Comprehensive ocular evaluation is important in this species and serial ocular exams and future studies should be pursued to monitor ocular disease progression and better understand possible etiologies.

Establishing an hTERT-driven immortalized umbilical cord-derived mesenchymal stem cell line and its therapeutic application in mice with liver failure.

Acute liver failure (ALF) is characterized by rapid liver cell destruction. It is a multi-etiological and fulminant complication with a clinical mortality of over 80%. Therapy using mesenchymal stem cells (MSCs) or MSCs-derived exosomes can alleviate acute liver injury, which has been demonstrated in animal experiments and clinical application. However, similar to other stem cells, different cell sources, poor stability, cell senescence and other factors limit the clinical application of MSCs. To achieve mass production and quality control on stem cells and their exosomes, transfecting umbilical cord mesenchymal stem cell (UCMSC) with lentivirus overexpressing human telomerase reverse transcriptase (hTERT) gene, the hTERT-UCMSC was constructed as an immortalized MSC cell line. Compared with the primary UCMSC (P3) and immortalized cell line hTERT-UCMSC at early passage (P10), the hTERT-UCMSC retained the key morphological and physiological characteristics of UCMSC at the 35th passage (P35), and showed no signs of carcinogenicity and toxic effect in mice. There was no difference in either exosome production or characteristics of exosomes among cultures from P3 primary cells, P10 and P35 immortalized hTERT-UCMSCs. Inoculation of either hTERT-UCMSC (P35) or its exosomes improved the survival rate and liver function of ALF mice induced by thioacetamide (TAA). Our findings suggest that this immortalized cell line can maintain its characteristics in long-term culture. Inoculation of hTERT-UCMSC and its exosomes could potentially be used in clinics for the treatment of liver failure in the future.

Sesquiterpene lactones improve secretory diarrhea symptoms by inhibiting intestinal Ca2+-activated Cl- channel activities directly and indirectly.

Secretory diarrhea caused by bacteria and viruses is usually accompanied by activation of the cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated Cl- channels (CaCCs) in the intestinal epithelium. Inhibition of CFTR and CaCCs activities significantly reduces fluid losses and intestinal motility in diarrheal diseases. For this reason, CFTR and CaCCs are potential targets of therapeutic drug screening. Here, we reported that the sesquiterpene lactones, alantolactone (AL) and isoalantolactone (iAL), significantly inhibited ATP and Eact-induced short-circuit currents in T84, HT-29 and Fischer rat thyroid (FRT) cells expressing transmembrane protein 16A (TMEM16A) in a concentration-dependent manner. AL and iAL also inhibited the CaCC-mediated short-circuit currents induced by carbachol in the mouse colons. Both compounds inhibited forskolin-induced currents in T84 cells but did not significantly affect mouse colons. In vivo studies indicated that AL and iAL attenuated gastrointestinal motility and decreased watery diarrhea in rotavirus-infected neonatal mice. Preliminary mechanism studies showed that AL and iAL inhibited CaCCs at least partially by inhibiting Ca2+ release and basolateral membrane K+ channels activity. These findings suggest a new pharmacological activity of sesquiterpene lactone compounds that might lead to the development of treatments for rotaviral secretory diarrhea.

Multimorbidity and polypharmacy in hospitalized older patients: a cross-sectional study.

BACKGROUND: The growing trend of ageing population has become a worldwide concern. In comparison with the youth, older people are more likely to suffer from multimorbidity and polypharmacy, both of which are associated with adverse outcomes and increased healthcare costs. This study aimed to investigate the status of multimorbidity and polypharmacy in a large sample of hospitalized older patients aged 60 years and over. METHODS: A retrospective cross-sectional study was conducted among 46,799 eligible patients aged 60 years and over, who were hospitalized from January 1, 2021 to December 31, 2021. Multimorbidity was defined as the presence of 2 or more morbidities in one patient during the stay in hospital, and polypharmacy as prescription of 5 or more different oral medications. Spearman rank correlation analysis was used to assess the relationship of factors with the number of morbidities or oral medications. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated from logistic regression models to determine the predictors for polypharmacy and all-cause death. RESULTS: The prevalence of multimorbidity was 91.07% and increased with age. The prevalence of polypharmacy was 56.32%. Older age, polypharmacy, prolonged length of stay (LOS), higher cost on medications were significantly associated with an increased number of morbidities (all P < 0.01). The number of morbidities (OR = 1.29, 95% CI: 1.208-1.229) and LOS (OR = 1.171, 95% CI: 1.166-1.177) were potential risk factors for polypharmacy. As for all-cause death, age (OR = 1.107, 95% CI: 1.092-1.122), number of morbidities (OR = 1.495, 95% CI: 1.435-1.558) and LOS (OR = 1.020, 95% CI: 1.013-1.027) were the potential risk factors, but the number of medications (OR = 0.930, 95% CI: 0.907-0.952) and polypharmacy (OR = 0.764, 95% CI: 0.608-0.960) were associated with a reduction of mortality. CONCLUSION: Morbidities and LOS might be predictors for polypharmacy and all-cause death. The number of oral medications was inversely associated with the risk of all-cause mortality. Appropriate polypharmacy was beneficial for the clinical outcomes of older patients during hospitalization.

The most common types of uroliths larger than 1 mm are readily visible and accurately measured in an in vitro setting mimicking the canine abdomen using digital radiography.

Abdominal radiography is an important diagnostic to detect uroliths. Cystine and urate uroliths were historically characterized as nonmineral opaque on survey radiographs. However, recent research and clinical observations indicate that pure urate and cystine uroliths may be detected with digital radiography. The primary purpose of this prospective, in vitro, diagnostic accuracy study was to determine the sensitivity of digital radiography in detecting cystoliths of varying size and composition. Forty canine uroliths of pure composition (10 each of calcium oxalate, struvite, cystine, and urate), acquired from Minnesota Urolith Center and ranging from 1 to 10 mm, were placed in phantoms of three various sizes and radiographed. The radiographs, including three sets of each urolith separately, were evaluated by three blinded radiologists on two separate occasions. Evaluation included presence or absence of urolith, number of uroliths, and maximum diameter of the urolith(s). For all four types of uroliths and all readers, the specificity and PPV were 100% with an associated very high sensitivity (94.4%-98.9%) and NPV (94.8%-98.9%). Calcium oxalate uroliths were the most accurately measured and struvite were the least accurately measured when compared with the gross measurement. Smaller uroliths were more accurately measured than larger uroliths. Uroliths placed in smaller bladder phantoms were more accurately measured than in larger bladder phantoms. Though accurate measurement of uroliths is complicated by and dependent on numerous variables, our results reveal that urate and cystine uroliths are visualized on digital radiography making them a relevant differential diagnosis when seen clinically.

Embelin protects against apoptosis and inflammation by regulating PI3K/Akt signaling in IL-1ß-stimulated human nucleus pulposus cells.

Embelin is a natural benzoquinone compound that displays a beneficial effect in various inflammatory-related diseases. However, the effect of embelin on degeneration of intervertebral disc (IDD), a chronic inflammatory disorder, has not been reported. This study was attempted to explore the therapeutic action of embelin on IDD in vitro. Network pharmacology analysis was performed for evaluating the link between embelin and IDD. The human nucleus pulposus cells (NPCs) were stimulated with IL-1ß to induce inflammation. Cell viability of NPCs was assessed by CCK-8 assay. Western blotting was conducted to detect the expression levels of PI3K, p-PI3K, Akt, p-Akt, cleaved caspase-3, caspase-3, Bax, Bcl-2, p65 and p-p65. Apoptotic deaths of NPCs were examined by TUNEL assay. The production of COX-2, IL-6, IL-8, and TNF-α was examined by ELISA. It can be seen that 16 overlapping genes were selected from 109 possible targets of embelin and 342 possible targets of IDD. KEGG pathway enrichment analysis showed that the PI3K/Akt signaling pathway was a close link between embelin and IDD. We found that embelin dose-dependently improved the cell viability in IL-1ß-stimulated NPCs. Embelin elevated the relative levels of p-PI3K/PI3K and p-Akt/Akt in IL-1ß-stimulated NPCs. IL-1ß induced a significant increase in apoptotic deaths of NPCs, which was attenuated by embelin treatment. IL-1ß-induced alternations in expression levels of apoptotic-related proteins including cleaved caspase-3, Bax and Bcl-2 were prevented by embelin treatment. Pretreatment with LY294002 (an inhibitor of PI3K) reversed the inhibitory effect of embelin on IL-1ß-induced apoptosis in NPCs. Embelin treatment caused inhibitory effects on the IL-1ß-stimulated production of COX-2, IL-6, IL-8, and TNF-α, which were abolished by LY294002 treatment. Furthermore, embelin treatment prevented IL-1ß-induced phosphorylation of p65 in NPCs, while LY294002 elevated the embelin-caused decrease in p-p65/p65 level. Overall, embelin protected human NPCs against IL-1ß-stimulated apoptosis and inflammation by regulating the PI3K/Akt signaling pathway. These findings provided new ideas for the clinical usage of embelin in the prevention and treatment of IDD.

All-trans retinoic acid inhibits oxidative stress via ACE2/Ang (1-7)/MasR pathway in renal tubular epithelial cells stimulated with high glucose.

The aim of this study was to investigate the effects of all-trans retinoic acid (atRA) on oxidative stress in renal tubular epithelial cells induced by high glucose (HG) and its potential mechanism. We investigated the effects of atRA in HG-induced renal epithelial cell line HK-2. Seven groups were designed for this experiment: negative control, mannitol, high-glucose (HG), HG combined with a low concentration of atRA, HG combined with a middle concentration of atRA, HG combined with a high concentration of atRA, and HG combined with captopril. After 48 h of incubation, oxidative stress factor expression in the supernatant was detected by enzyme-linked immunosorbent assay. Reactive oxygen species and cell apoptosis expression were assessed by flow cytometry. NADPH oxidase, fibrosis factor, and angiotensin-converting enzyme 2/angiotensin (1-7)/mas receptor (ACE2/Ang (1-7)/MasR) pathway-related protein expressions were determined by western blot analysis. The expressions of oxidative stress factors, NADPH oxidase components, and fibrosis factors were significantly higher after HG treatment. Apoptosis of HK2 cells in the HG group was also significantly higher. AtRA could reverse the above abnormal changes in a concentration-dependent manner. HG significantly promoted the expression of ACE, Ang II, and Ang II type 1 receptor (AT1R), whereas it inhibited the expression of ACE2, Ang (1-7), and MasR. With the elevation of concentration, atRA could gradually suppress the expression of ACE, Ang II, and AT1R, but facilitate ACE2, Ang (1-7), and MasR. These results were statistically significant. AtRA could significantly inhibit oxidative stress and apoptosis of renal tubular epithelial cells induced by HG. The mechanism may inhibit the ACE/Ang II/AT1R pathway and/or activate ACE2/Ang (1-7)/MasR pathway.

Schisandrin B Improves the Hypothermic Preservation of Celsior Solution in Human Umbilical Cord Mesenchymal Stem Cells.

BACKGROUND: Human umbilical cord mesenchymal stem cells (hUCMSCs) have emerged as promising therapy for immune and inflammatory diseases. However, how to maintain the activity and unique properties during cold storage and transportation is one of the key factors affecting the therapeutic efficiency of hUCMSCs. Schisandrin B (SchB) has many functions in cell protection as a natural medicine. In this study, we investigated the protective effects of SchB on the hypothermic preservation of hUCMSCs. METHODS: hUCMSCs were isolated from Wharton's jelly. Subsequently, hUCMSCs were exposed to cold storage (4 °C) and 24-h re-warming. After that, cells viability, surface markers, immunomodulatory effects, reactive oxygen species (ROS), mitochondrial integrity, apoptosis-related and antioxidant proteins expression level were evaluated. RESULTS: SchB significantly alleviated the cells injury and maintained unique properties such as differentiation potential, level of surface markers and immunomodulatory effects of hUCMSCs. The protective effects of SchB on hUCMSCs after hypothermic storage seemed associated with its inhibition of apoptosis and the anti-oxidative stress effect mediated by nuclear factor erythroid 2-related factor 2 signaling. CONCLUSION: These results demonstrate SchB could be used as an agent for hypothermic preservation of hUCMSCs.

Baicalin suppresses interleukin-1ß-induced apoptosis, inflammatory response, oxidative stress, and extracellular matrix degradation in human nucleus pulposus cells.

OBJECTIVE: To explore the effect of baicalin on human nucleus pulposus cells (NPCs) in response to interleukin (IL)-1ß stimulation. METHODS: Viability of NPCs was measured by cell counting kit-8 (CCK-8) assay. TUNEL staining assay and flow cytometry were performed to detect apoptotic cell death of NPCs. Western blot analysis was conducted to detect the expression levels of proteins. Enzyme-linked immunosorbent assay (ELISA) was applied for the determination of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), and IL-6. Oxidative stress indicators including reactive oxygen species (ROS) production, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity were measured. RESULTS: Baicalin attenuated IL-1ß-caused cell viability reduction and apoptosis in NPCs. IL-1ß-induced increase in Bax expression and decrease in Bcl-2 expression were attenuated by baicalin treatment. IL-1ß-induced production of iNOS, COX-2, IL-6, and TNF-α in NPCs was inhibited by baicalin treatment. Baicalin treatment reversed IL-1ß-induced increase in ROS production and MDA level, as well as decrease in SOD activity. Furthermore, baicalin treatment elevated the expression levels of Col II and Aggrecan and downregulated the expression levels of MMP3, MMP13, and ADAMTS5 in IL-1ß-induced NPCs. A total of 402 related targets of baicalin and 134 related targets of intervertebral disk degeneration were found, and nine intersection targets were screened out. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that mitogen-activated protein kinase (MAPK) pathway was found to be involved in the effects of baicalin. CONCLUSIONS: Baicalin exhibited protective effects on IL-1ß-caused cell viability reduction, apoptosis, oxidative stress, inflammation, and extracellular matrix degradation in NPCs. In addition, we found c-Jun N-terminal kinase (JNK) and p38 MAPK pathways as targets of baicalin through bioinformatic analysis.

Emodin protects against apoptosis and inflammation by regulating reactive oxygen species-mediated NF-κB signaling in interleukin-1ß-stimulated human nucleus pulposus cells.

Intervertebral disc degeneration (IDD) is a complex degradative disorder associated with inflammation. Emodin, an anthraquinone derivative, possesses strong anti-inflammatory activity. This study focused on the in vitro therapeutic action of emodin in a cellular model of IDD. Human nucleus pulposus cells (NPCs) were stimulated with interleukin-1ß (IL-1ß) to induce inflammation. Cell Counting Kit-8 and terminal deoxynucleotidyl transferase dUTP nick end labeling staining assays were performed to evaluate the viability and apoptosis of NPCs, respectively. Caspase-3 activity was measured to indirectly assess cell apoptosis. Western blot analysis was performed to detect protein expression levels. Reverse transcription-polymerase chain reaction was performed for the detection of relative mRNA levels of tumor necrosis factor-α (TNF-α) and IL-6. Enzyme-linked immunosorbent assay was performed to analyze TNF-α and IL-6 secretion. Our results showed that emodin treatment mitigated IL-1ß-induced reduction of cell viability in NPCs. Moreover, the increase in reactive oxygen species (ROS) production, apoptotic rate, and caspase-3 activity in IL-1ß-stimulated NPCs was reduced by emodin treatment. Treatment with emodin also abolished IL-1ß-induced inflammation in NPCs, as indicated by reduced secretion of IL-6 and TNF-α. Besides, the increase in expression levels of phosphorylated p65 and nuclear p65 in IL-1ß-stimulated NPCs was suppressed by emodin treatment. Furthermore, inhibition of nuclear factor kappa B (NF-κB) activation with pyrrolidine dithiocarbamate aggravated the protective effects of emodin. These results suggested that emodin protected NPCs against IL-1ß-induced apoptosis and inflammation via inhibiting ROS-mediated activation of NF-κB.

Inducing trained immunity in pro-metastatic macrophages to control tumor metastasis.

Metastasis is the leading cause of cancer-related deaths and myeloid cells are critical in the metastatic microenvironment. Here, we explore the implications of reprogramming pre-metastatic niche myeloid cells by inducing trained immunity with whole beta-glucan particle (WGP). WGP-trained macrophages had increased responsiveness not only to lipopolysaccharide but also to tumor-derived factors. WGP in vivo treatment led to a trained immunity phenotype in lung interstitial macrophages, resulting in inhibition of tumor metastasis and survival prolongation in multiple mouse models of metastasis. WGP-induced trained immunity is mediated by the metabolite sphingosine-1-phosphate. Adoptive transfer of WGP-trained bone marrow-derived macrophages reduced tumor lung metastasis. Blockade of sphingosine-1-phosphate synthesis and mitochondrial fission abrogated WGP-induced trained immunity and its inhibition of lung metastases. WGP also induced trained immunity in human monocytes, resulting in antitumor activity. Our study identifies the metabolic sphingolipid-mitochondrial fission pathway for WGP-induced trained immunity and control over metastasis.

Preventive treatment with sodium para-aminosalicylic acid inhibits manganese-induced apoptosis and inflammation via the MAPK pathway in rat thalamus.

Excessive exposure to manganese (Mn) may lead to neurotoxicity, referred to as manganism. In several studies, sodium para-aminosalicylic acid (PAS-Na) has shown efficacy against Mn-induced neurodegeneration by attenuating the neuroinflammatory response. The present study investigated the effect of Mn on inflammation and apoptosis in the rat thalamus, as well as the underlying mechanism of the PAS-Na protective effect. The study consisted of sub-acute (Mn treatment for 4 weeks) and sub-chronic (Mn and PAS-Na treatment for 8 weeks) experiments. In the sub-chronic experiments, pro-inflammatory cytokines, namely tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and cyclooxygenase 2 (COX-2) were significantly increased in the Mn-exposed group compared to the control II. PAS-Na treatment led to a significant reduction in the Mn-induced neuroinflammation by inhibiting IL-1ß and COX-2 mRNA expression and reducing IL-1ß secretion and JNK/p38 MAPK pathway activity. Furthermore, immunohistochemical analysis showed that the expression of caspase-3 was significantly increased in both the sub-acute and sub-chronic experimental paradigms concomitant with a significant decrease in B-cell lymphoma 2 (Bcl-2) in the thalamus of Mn-treated rats. PAS-Na also decreased the expression levels of several apoptotic markers downstream of the MAPK pathway, including Bcl-2/Bax and caspase-3, while up-regulating anti-apoptotic Bcl-2 proteins. In conclusion, Mn exposure led to inflammation in the rat thalamus concomitant with apoptosis, which was mediated via the MAPK signaling pathway. PAS-Na treatment antagonized effectively Mn-induced neurotoxicity by inhibiting the MAPK activity in the same brain region.

Evaluation of potentially inappropriate medications for the elderly according to beers, STOPP, START, and Chinese criteria.

Objective: Polypharmacy prevalence is increasing worldwide, and it is becoming more popular among the elderly. This study aimed to compare the prevalence of potentially inappropriate medications (PIMs) using the Beers criteria (2019 edition), criteria for potentially inappropriate medications for older adults in China (Chinese criteria), Screening Tool of Older Persons' Prescriptions (STOPP), and Screening Tool to Alert to Right Treatment (START) criteria and to identify risk factors associated with PIM use. Methods: This was a cross-sectional study with a sample of 276 inpatients aged ≥65 years old from January 2020 to June 2020. A cross-sectional study was conducted to analyze PIMs based on the Beers (2019 edition), Chinese, STOPP, and START criteria. PIMs use was analysed based on four different criteria and logistic regression analysis was used to investigate independent factors associated with PIM use. Results: The mean number of medications used by the elderly population was nine (range, 0-28). A total of 252 patients (accounting for 91.30%) took five or more medications and 120 patients (accounting for 43.48%) took 10 or more medications. The prevalence rates of PIMs were 66.30% (183/276), 55.07% (152/276), 26.45% (73/276), and 64.13% (177/276) determined by the Beers, Chinese, STOPP, and START criteria, respectively. The top PIMs screened using the Beers, Chinese, and STOPP criteria were proton pump inhibitors, clopidogrel, and benzodiazepines, respectively. Missed use of ACEI in patients with systolic heart failure and/or coronary artery disease was found to be the most common potential prescription omission (PPOs) analyzed using the START criteria. Logistic regression analysis showed that the strongest predictor of PIMs, as determined by all four criteria, was an increased number of medications (p < 0.001). Age was another risk factor for PIMs based on the STOPP criteria in our study (p < 0.05). Conclusion: Polypharmacy and PIMs were common in our study, and the risk of PIMs correlated with polypharmacy. Application of the Beers, Chinese, STOPP, and START criteria is a useful tool for detecting PIM use.

Evaluation of Concurrent Chemoradiotherapy for Survival Outcomes in Patients With Synchronous Oligometastatic Esophageal Squamous Cell Carcinoma.

Importance: The optimal treatment for and potential benefit populations of synchronous oligometastatic esophageal squamous cell carcinoma (SOESCC) remain unclear. Objectives: To evaluate outcomes of concurrent chemoradiotherapy (CCRT) and to construct decision tree models for predicting the risk of progression and mortality in patients with SOESCC. Design, Setting, and Participants: This prognostic study included 532 patients with SOESCC who were treated at 2 cancer centers in China from January 2012 to December 2018 and consisted of a development cohort (n = 381) and a validation cohort (n = 151). Data were analyzed from March 2019 to December 2021. Exposures: All patients received chemotherapy alone or CCRT. Main Outcomes and Measures: The primary end points of the study were progression-free survival (PFS) and overall survival (OS), and the secondary end points were locoregional control and treatment-related toxic effects. Propensity score matching was performed to control potential confounding factors. Cox regression was used to screen important explanatory variables. Decision trees for optimally partitioning patients were established using recursive partitioning analysis and were then subjected to internal and independent external validation. Results: Among the 532 patients (median [range] age, 63 [32-82] years; 367 men [69.0%]), 292 patients received chemotherapy alone and 240 patients underwent CCRT. With a median (IQR) follow-up time of 37.0 (21.6-55.8) months, CCRT was associated with improved objective response rate (139 of 240 [57.9%] vs 123 of 292 [42.1%]; P < .001), median (IQR) PFS (9.7 [8.5-10.9] months vs 7.6 [6.6-8.6] months; P < .001), and median (IQR) OS (18.5 [16.1-20.9] months vs 15.2 [13.6-16.8] months; P < .001) compared with chemotherapy alone. Propensity score matching analysis verified the results. Cox multivariate analysis indicated that treatment modality (CCRT vs chemotherapy alone) was an independent prognostic factor related to PFS (hazard ratio, 0.69; 95% CI, 0.57-0.83; P < .001) and OS (hazard ratio, 0.75; 95% CI, 0.61-0.93; P = .008). The final decision trees divided patients with SOESCC into low-, intermediate-, and high-risk groups in both the internal and external validations, and the corresponding cumulative risk function curves had significant differences (all P < .001). Time-dependent maximum areas under receiver operating curves of decision trees for progression risk at 3 years and mortality risk at 5 years were 0.820 (95% CI, 0.693-0.948) and 0.894 (95% CI, 0.822-0.966), respectively. Calibration curves also demonstrated that the decision trees had favorable performance of risk stratification. Conclusions and Relevance: In this study, CCRT vs chemotherapy alone as a first-line treatment for patients with SOESCC had superior survival. Patients with low risk had promising long-term survival based on the current treatment modality. The predictive information of the decision tree could provide accurate decision-making for the management of patients with SOESCC.

Effects of endoscopic therapy and surgical resection on long-term survival outcomes in patients with duodenal gastrointestinal stromal tumors: a surveillance, epidemiology, and end result program analysis.

BACKGROUND: With the rapid development of endoscopic technology, endoscopic therapy (ET) has gradually become a new treatment choice for gastrointestinal stromal tumors (GISTs). However, due to the low incidence of duodenal GIST and the difficulty of ET, there is a lack of data to compare the long-term results of ET and surgical resection. METHODS: Duodenal GIST patients from 2004 to 2015 were selected from the surveillance, epidemiology, and end result (SEER) database. We used the Kaplan-Meier method and log-rank test to describe the 5- and 10-year survival differences between the ET and the surgery groups. The multivariate Cox proportional hazard model was used for analyzing the risk factors influencing the prognosis of patients. We used a 1:1 propensity score-matched (PSM) to reduce confounding factors, and then we compared survival differences between the two groups again. RESULTS: A total of 294 patients with duodenal GIST were enrolled, including 41 (13.9%) patients with ET and 253 (86.1%) patients with surgical resection. Before PSM, the long-term survival of patients with duodenal GIST after ET and surgical resection was similar [5-year overall survival (OS) (79.7 vs. 79.3%, p = 0.876), 10-year OS (66.5 vs. 68.1%, p = 0.876)]. After adjusting the relevant variables using multivariate Cox analysis, we found that the ET and surgery groups were comparable in OS and cancer-specific survival (CSS). After PSM, there was also no significant difference between ET and surgical resection for long-term OS and CSS. CONCLUSION: Our study found no significant difference in long-term survival between ET and surgical resection in patients with duodenal GIST. However, to obtain high-quality evidence, more extensive sample size studies are needed in the future to evaluate the long-term effects of ET on patients.

Comparison of steroid and thyroid hormone concentrations in blood serum and plasma of captive tigers.

Analysis of steroid and thyroid hormones is often performed in blood serum. Occasionally though, plasma samples are submitted in lieu of serum for exotic species such as tigers. However, blood tube anticoagulants may affect hormone values. We compared serum and heparin plasma results for 7 hormones in tigers. Serum and plasma samples were collected from 25 tigers and analyzed for progesterone, 17-hydroxyprogesterone, cortisol, androstenedione, testosterone, estradiol, and thyroxine. Using Lin concordance correlation, serum and heparin plasma measures agreed for all hormones except cortisol. However, Passing-Bablok regression only found agreement between serum and heparin plasma measures for androstenedione, testosterone, and estradiol. Median values between the 2 sample types were significantly (p < 0.05) different for progesterone, 17-hydroxyprogesterone, cortisol, and thyroxine. Our results suggest that, for the aforementioned hormones, serum and heparin plasma values may not always be comparable.

Cyanidin attenuates the apoptosis of rat nucleus pulposus cells and the degeneration of intervertebral disc via the JAK2/STAT3 signal pathway in vitro and in vivo.

CONTEXT: Cyanidin has been shown to have therapeutic potential in osteoarthritis. However, it is unclear whether cyanidin prevents the progression of intervertebral disc degeneration (IVDD). OBJECTIVE: This study evaluates the effects of cyanidin on IVDD in vitro and in vivo. MATERIALS AND METHODS: Nucleus pulposus cells (NPCs) isolated from lumbar IVD of 4-week-old male Sprague-Dawley (SD) rats were exposed to 20 ng/mL IL-1ß, and then treated with different doses (0-120 µM) of cyanidin for 24 h. SD rats were classified into three groups (n = 8) and treated as follows: control (normal saline), IVDD (vehicle), IVDD + cyanidin (50 mg/kg). Cyanidin was administered intraperitoneally for 8 weeks. RESULTS: The IC50 of cyanidin for NPCs was 94.78 µM, and cyanidin had no toxicity at concentrations up to 500 mg/kg in SD rats. Cyanidin inhibited the apoptosis of NPCs induced by IL-1ß (12.73 ± 0.61% vs. 18.54 ± 0.60%), promoted collagen II (0.82-fold) and aggrecan (0.81-fold) expression, while reducing MMP-13 (1.02-fold) and ADAMTS-5 (1.40-fold) expression. Cyanidin increased the formation of autophagosomes in IL-1ß-induced NPCs, and promoted LC3II/LC3I (0.83-fold) and beclin-1 (0.85-fold) expression, which could be reversed by chloroquine. Cyanidin inhibited the phosphorylation of JAK2 (0.47-fold) and STAT3 (0.53-fold) in IL-1ß-induced NPCs. The effects of cyanidin could be enhanced by AG490. Furthermore, cyanidin mitigated disc degeneration in IVDD rats in vivo. DISCUSSION AND CONCLUSIONS: Cyanidin improved the function of NPCs in IVDD by regulating the JAK2/STAT3 pathway, which may provide a novel alternative strategy for IVDD. The mechanism of cyanidin improving IVDD still needs further work for in-depth investigation.