The impact of skeletal muscle index at the third lumbar spine on nosocomial deterioration and short-term prognosis in acute pancreatitis: a retrospective observational study.

Objective: To investigate the impact of the third lumbar skeletal muscle index (L3-SMI) assessed by CT on the in-hospital severity and short-term prognosis of acute pancreatitis. Methods: A total of 224 patients with severe acute pancreatitis admitted to Yantaishan Hospital from January 2021 to June 2022 were selected as the subjects. Based on the in-hospital treatment outcomes, they were divided into a mortality group of 59 cases as well as a survival group of 165 cases. Upon admission, general information such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, along with the abdominal CT images of each patient, were analyzed. The L3-SMI was calculated, and the Modified CT Severity Index (MCTSI) and Balthazar CT grade were used to assess the severity of in-hospital complications of acute pancreatitis. The evaluation value of L3-SMI for the prognosis of severe acute pancreatitis was analyzed, as well as the factors influencing the prognosis of severe acute pancreatitis. Results: No statistically significant differences in gender, age, BMI, etiology, duration of anti-inflammatory drug use, and proportion of surgical patients between the survival and mortality groups were observed. But the mortality group showed higher proportions of patients with an elevated APACHE II score upon admission, mechanical ventilation, and renal replacement therapy, compared to the survival group, with statistically significant differences (P < 0.001). Furthermore, the mortality group had higher MCTSI scores (6.42 ± 0.69) and Balthazar CT grades (3.78 ± 0.45) than the survival group, with statistically significant differences (P < 0.001). The mortality group also had a lower L3-SMI (39.68 ± 3.25) compared to the survival group (42.71 ± 4.28), with statistically significant differences (P < 0.001). L3-SMI exhibited a negative correlation with MCTSI scores and Balthazar CT grades (r = -0.889, -0.790, P < 0.001). Logistic regression analysis, with mortality of acute pancreatitis patients as the dependent variable and MCTSI scores, Balthazar CT grades, L3-SMI, APACHE II score upon admission, mechanical ventilation, and renal replacement therapy as independent variables, revealed that MCTSI scores and L3-SMI were risk factors for mortality in acute pancreatitis patients (P < 0.001). Logistic regression analysis using the same variables confirmed that all these factors were risk factors for mortality in acute pancreatitis patients. Conclusion: This study confirmed that diagnosing muscle depletion using L3-SMI is a valuable radiological parameter for predicting in-hospital severity and short-term prognosis in patients with acute pancreatitis.

Design, Synthesis, and Antitumor Efficacy of Substituted 2-Amino[1,2,4]triazolopyrimidines and Related Heterocycles as Dual Inhibitors for Microtubule Polymerization and Janus Kinase 2.

Preclinical and clinical studies have demonstrated the synergistic effect of microtubule-targeting agents in combination with Janus kinase 2 (JAK2) inhibitors, prompting the development of single agents with enhanced therapeutic efficacy by dually inhibiting tubulin polymerization and JAK2. Herein, we designed and synthesized a series of substituted 2-amino[1,2,4]triazolopyrimidines and related heterocycles as dual inhibitors for tubulin polymerization and JAK2. Most of these compounds exhibited potent antiproliferative activity against the selected cancer cells, with compound 7g being the most active. This compound effectively inhibits both tubulin assembly and JAK2 activity. Furthermore, phosphorylated compound 7g (i.e., compound 7g-P) could efficiently convert to compound 7g in vivo. Compound 7g, whether it was administered directly or in the form of a phosphorylated prodrug (i.e., compound 7g-P), significantly inhibited the growth of A549 xenografts in nude mice. The present findings strongly suggest that compound 7g represents a promising chemotherapeutic agent with high antitumor efficacy.

Comparison of ultrasonic shear wave elastography, AngioPLUS planewave ultrasensitive imaging, and optimized high-resolution magnetic resonance imaging in evaluating carotid plaque stability.

Objective: This study aimed to compare the efficiency of evaluating carotid plaque stability using ultrasonic shear wave elastography (SWE), AngioPLUS planewave ultrasensitive imaging (AP), and optimized high-resolution magnetic resonance imaging (MRI). Methods: A total of 100 patients who underwent carotid endarterectomy at our hospital from October 2019 to August 2022 were enrolled. Based on the final clinical diagnosis, these patients were divided into vulnerable (n = 62) and stable (n = 38) plaque groups. All patients were examined using ultrasound SWE, AP, and optimized high-resolution MRI before surgery. The clinical data and ultrasound characteristics of patients of the two groups were compared. Considering the final clinical diagnosis as the gold standard, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of SWE, AP, high-resolution MRI, and the final clinical diagnosis of vulnerable plaque were calculated. Pearson's correlation test was used to analyze the correlations of AP, SWE, and MRI results with the grading results of carotid artery stenosis. Results: Statistically significant differences were noticed in terms of the history of smoking and coronary heart disease, plaque thickness, surface rules, calcified nodules, low echo area, and the degree of carotid artery stenosis between the two groups (P < 0.05). Considering the final clinical diagnosis as the gold standard, the sensitivity, specificity, PPV, and NPV of SWE-based detection of carotid artery vulnerability were 87.10% (54/62), 76.32% (29/38), 85.71% (54/63) and 78.38% (29/37), respectively, showing a general consistency with the final clinical results (Kappa = 0.637, P < 0.05). Considering the final clinical diagnosis as the gold standard, the sensitivity, specificity, PPV and NPV of AP-based detection of carotid artery vulnerability were 93.55% (58/62), 84.21% (32/38), 90.63% (58/64), and 88.89% (32/36), respectively, which agreed with the final clinical detection results (Kappa = 0.786, P < 0.05). Considering the final clinical diagnosis as the gold standard, the sensitivity, specificity, PPV and NPV of high-resolution MRI-based detection of carotid artery vulnerability were 88.71% (55/62), 78.95% (30/38), 87.30% (55/63), and 81.08% (30/37), respectively, showing consistency with the final clinical results (Kappa = 0.680, P < 0.05). AP, SWE, and MRI results were positively correlated with the results of carotid artery stenosis grading (P < 0.05). Conclusion: AP technology is a non-invasive, inexpensive, and highly sensitive method to evaluate the stability of carotid artery plaques. This method can dynamically display the flow of blood in new vessels of plaque in real time and provide a reference for clinical diagnosis and treatment.

Mild moxibustion for Irritable Bowel Syndrome with Diarrhea (IBS-D): A randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Moxibustion therapy is a traditional Chinese medicine external treatment method, which involves crushing dried herb Artemisia argyi H. Lév. & Vanio and rolling it into a long cigarette-like strip, igniting it and using its warmth to stimulate specific acupuncture points for a certain period of time. It is often used in Asia to treat various diseases, especially abdominal pain. Clinical reports suggest that acupuncture and moxibustion are the effective treatment for Irritable Bowel Syndrome with Diarrhea (IBS-D). However, there is no placebo-controlled study to prove its safety and efficacy. OBJECTIVE: To evaluate the effects of mild moxibustion (MM) for the treatment of irritable bowel syndrome with diarrhea (IBS-D) through comparisons with those of placebo moxibustion. PATIENTS AND METHODS: This was a single-site, randomized controlled trial was conducted at Shanghai Research Institute of Acupuncture and Meridian in China and enrolled 76 participants who met the Rome IV diagnostic criteria for IBS-D between May 2017 and December 2019. 76 participants were randomized to either mild moxibustion (MM) or placebo moxibustion group (PM) in a 1:1 ratio. 18 sessions of MM or PM were implemented over the course of 6 weeks (3 times per week). The primary outcome was adequate relief after 6 weeks of treatment. RESULTS: Of 76 patients with IBS-D who were randomized (38 in the MM group and 38 in the PM group) were included in the intention-to-treat (ITT) analysis set. After treatment at week 6, the response rate was significantly higher in the MM group than the PM group (81.58% vs. 36.84%) with an estimated difference of 44.74 (95% CI, 23.46 to 66.02, P < 0.001). No participant reported severe adverse effects. CONCLUSION: The findings suggest that mild moxibustion may be more effective than placebo moxibustion for the treatment of IBS-D, with effects lasting up to 12 weeks. TRIAL REGISTRATION: ChiCTR, ChiCTR2100046852. Registered 29 May 2021 - Retrospectively registered, URL: http://www.chictr.org.cn/showproj.aspx?proj=127000.

Case Report: Treatment of Oral Lichen Planus With a Focus on Psychological Methods.

Oral lichen planus (OLP) is one of the most common chronic diseases; however, its etiology remains unknown. More and more studies have revealed that emotional instability is one of the risk factors for the onset and expansion of OLP, especially in patients suffering from depression, anxiety disorder, and acute stress. In this case report, we had a 32-year-old female OLP patient who had no obvious response to conventional OLP drugs. Then we switched to a combination of psychotropic drugs and psychotherapies. By regulating mood through drugs and psychological counseling, the patient's oral disease was alleviated. Our case shows that clinicians should consider the mental problems of OLP patients. It also emphasizes the importance of medications and psychological counseling in the treatment of somatic diseases.

Effect of mild moxibustion on intestinal microbiota and NLRP6 inflammasome signaling in rats with post-inflammatory irritable bowel syndrome.

BACKGROUND: About one-third of refractory irritable bowel syndrome (IBS) cases are caused by gastrointestinal (GI) infection/inflammation, known as post-infectious/post-inflammatory IBS (PI-IBS). Although it is known that intestinal microbiota and host NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammsome signaling are closely related to PI-IBS and moxibustion has a therapeutic effect on PI-IBS, whether moxibustion regulates the intestinal flora and host NLRP6 events in PI-IBS remains unclear. AIM: To examine the regulatory effect of moxibustion on intestinal microbiota and host NLRP6 inflammatory signaling in PI-IBS. METHODS: Sprague-Dawley rats were divided into a normal control group, a model control group, a mild moxibustion group, and a sham mild moxibustion group. PI-IBS rats in the mild moxibustion group were treated with moxibusiton at bilateral Tianshu (ST 25) and Zusanli (ST36) for 7 consecutive days for 10 min each time. The sham group rats were given the same treatment as the mild moxibustion group except the moxa stick was not ignited. Abdominal withdrawal reflex (AWR) score was measured to assess the visceral sensitivity, and colon histopathology and ultrastructure, colonic myeloperoxidase (MPO) activity, and serum C-reactive protein (CRP) level were measured to evaluate low-grade colonic inflammation in rats. The relative abundance of selected intestinal bacteria in rat feces was detected by 16S rDNA PCR and the NLRP6 inflammsome signaling in the colon was detected by immunofluorescence, qRT-PCR, and Western blot. RESULTS: The AWR score was significantly decreased and the low-grade intestinal inflammation reflected by serum CRP and colonic MPO levels was inhibited in the mild moxibustion group compared with the sham group. Mild moxibustion remarkably increased the relative DNA abundances of Lactobacillus, Bifidobacterium, and Faecalibacterium prausnitzii but decreased that of Escherichia coli in the gut of PI-IBS rats. Additionally, mild moxibustion induced mRNA and protein expression of intestine lectin 1 but inhibited the expression of IL-1ß, IL-18, and resistance-like molecule ß by promoting the NLRP6 and reducing the mRNA and protein expression of apoptosis-associated speck-like protein containing CARD (ASC) and cysteinyl-aspartate-specific proteinase 1 (Caspase-1). The relative DNA abundances of Lactobacillus, Bifidobacteria, Faecalibacterium prausnitzii, and Escherichia coli in each group were correlated with the mRNA and protein expression of NLRP6, ASC, and Caspase-1 in the colon. CONCLUSION: These findings indicated that mild moxibustion can relieve low-grade GI inflammation and alleviate visceral hypersensitivity in PI-IBS by regulating intestinal microbes and controlling NLRP6 inflammasome signaling.

Effects of Xingpi Kaiyu Fang on ATP, Na/K-ATPase, and Respiratory Chain Complexes of Hippocampus and Gastrocnemius Muscle in Depressed Rats.

OBJECTIVE: To clarify the effectiveness and mechanism of the Chinese herbal formula Xingpi Kaiyu Fang (XPKYF) which is composed of American ginseng (Xi-Yang-shen), Radix curcumae (Yu-Jin), Acori tatarinowii rhizoma (Shi-Chang-pu), and Hypericum perforatum (Guan-Ye-lian-qiao) in depressed rats. METHODS: The rat model of depression was established by chronic unpredictable mild stress (CUMS) method for 6 weeks. Rats were randomly divided into six groups: control group, CUMS group, CUMS+XPKYF (3.6g/kg/d, 7.2g/kg/d, 14.4g/kg/d) groups, and CUMS+sertraline (4.5mg/kg/d) group. The sucrose preference test and the forced swimming test were performed to assess the rats' depression behavior. Mitochondrial ultrastructure was observed by transmission electron microscope and adenosine triphosphate (ATP) content, sodium potassium ATPase (Na/K-ATPase) activity, and mitochondrial respiratory chain complexes activities in hippocampus and gastrocnemius muscle were measured at the 14th and 42nd day. RESULTS: Rats subjected to six weeks of CUMS exhibited decreased sucrose preference ratio and prolonged immobility time. CUMS reduced ATP content in hippocampus, decreased Na/K-ATPase activity and respiratory chain complex I, III, and IV activities in hippocampus and gastrocnemius muscle, and damaged mitochondrial ultrastructure of hippocampus and gastrocnemius muscle. XPKYF at 14.4g/kg, the efficacy trend of which was better than the other drug groups, could prevent the stress-induced depressed behavior changes, inhibit the decrease of Na/K-ATPase activity in hippocampus, inhibit the decrease of respiratory chain complex III activities in hippocampus and gastrocnemius muscle, and protect mitochondria from ultrastructural damage. CONCLUSIONS: Energy deficiency and damaged mitochondrial ultrastructure were found in hippocampus and gastrocnemius muscle of depressed rats established by CUMS. XPKYF could partly reverse alterations in ATP, Na/K-ATPase, and respiratory chain complexes of hippocampus and gastrocnemius muscle and protect mitochondria from ultrastructural damage. This provides another experimental evidence for the clinical application of XPKYF in the treatment of depression.

Effect of XingPiJieYu decoction on spatial learning and memory and cAMP-PKA-CREB-BDNF pathway in rat model of depression through chronic unpredictable stress.

BACKGROUND: Depression is a mental disorder characterized by a pervasive low mood and loss of pleasure or interest in usual activities, and often results in cognitive dysfunction. The disturbance of cognitive processes associated with depression, especially the impairment of learning and memory, exacerbates illness and increases recurrence of depression. XingPiJieYu (XPJY) is one of the most widely clinical formulas of traditional Chinese medicine (TCM) and can improve the symptoms of depression, including learning and memory. However, its regulatory effects haven't been comprehensively studied so far. Recently, some animal tests have indicated that the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element-binding protein (CREB)-brain derived neurotrophic factor (BDNF) signaling pathway in hippocampus is closely related to depression and the pathogenesis of cognitive function impairments. The present study was performed to investigate the effect and mechanism of XPJY on depression and learning and memory in animal model. MATERIALS: The rat model of depression was established by chronic unpredictable stress (CUS) for 21 days. The rats were randomly divided into six groups: control group, CUS group, CUS + XPJY (1.4 g/kg, 0.7 g/kg and 0.35 g/kg) groups, and CUS + sertraline (10 mg/kg) group. The sucrose preference, open field exploration and Morris water maze (MWM) were tested. The expression of cAMP, CREB, PKA and BDNF protein in hippocampus was examined with Elisa and Western Blot. The mRNA level of CREB and BDNF in hippocampus was measured with PCR. RESULTS: The results demonstrated that rats subjected to CUS exhibited decreases in sucrose preference, total ambulation, percentage of central ambulation, rearing in the open field test and spatial performance in the MWM. CUS reduced the expression of cAMP, PKA, CREB and BDNF in hippocampus of model rats. These effects could be reversed by XPJY. CONCLUSION: The results indicated that XPJY can improve depression and related learning and memory and the effect of XPJY is partly exerted through the cAMP-PKA-CREB-BDNF signaling pathway.

A Hybrid Approach to Extracting Disorder Mentions from Clinical Notes.

Crucial information on a patient's physical or mental conditions is provided by mentions of disorders, such as disease, syndrome, injury, and abnormality. Identifying disorder mentions is one of the most significant steps in clinical text analysis. However, there are many surface forms of the same concept documented in clinical notes. Some are even recorded disjointedly, briefly, or intuitively. Such difficulties have challenged the information extraction systems that focus on identifying explicit mentions. In this study, we proposed a hybrid approach to disorder extraction, which leverages supervised machine learning, rule-based annotation, and an unsupervised NLP system. To identify different surface forms, we exploited rich features, especially the semantic, syntactic, and sequential features, for better capturing implicit relationships among words. We evaluated our method on the CLEF 2013 eHealth dataset. The experiments showed that our hybrid approach achieves a 0.776 F-score under strict evaluation standards, outperforming any participating systems in the Challenge.

Synthesis and blocking activities of isoindolinone- and isobenzofuranone-containing phenoxylalkylamines as potent α(1)-adrenoceptor antagonists.

This paper describes the synthesis and blocking activities of twelve new isoindolinone- and isobenzofuranone-containing phenoxylalkylamines as potent α(1)-Adrenoceptor antagonists. These compounds were synthesized in moderate to good yields starting from 3,4-dimethylphenol, and characterized with (1)H-NMR, MS, IR and elemental analysis. Their blocking activities toward α(1)-Adrenoceptors were evaluated on isolated rat anococcygeus muscles. The results indicated that these compounds were very strong in blocking α(1)-Adrenoceptors, and most of them exhibited activities that were comparable to that of known potent α(1)-Adrenoceptor antagonist 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane hydrochloride (DDPH).