OBJECTIVES: Psoriasis is associated with lipid metabolism disorders, but the underlying mechanisms remain unclear. This study aims to investigate the role of trimethylamine N-oxide (TMAO) in lipid metabolism dysregulation in psoriasis. METHODS: An imiquimod (IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters, TMAO levels, and liver flavin monooxygenase 3 (FMO3) mRNA expression. Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles. To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model, exogenous TMAO, choline, or 3,3-dimethyl-1-butanol (DMB) were administered via intraperitoneal injections or diet in IMQ-treated mice. Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways. RESULTS: IMQ-induced psoriatic mice exhibited abnormal glucose, insulin, and lipid levels. IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2 (Glut2) and silence information regulator 1 (Sirt1), while upregulating glucose transporter 4 (Glut4) and peroxisome proliferator-activated receptor gamma (PPARγ). Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice. Additionally, liver FMO3 mRNA expression was increased in the psoriatic mouse model. In patients, TMAO levels positively correlated with Psoriasis Area and Severity Index (PASI) scores, serum triglyceride (TG), and total cholesterol (TC) levels. The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice. A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice, whereas DMB treatment alleviated these effects. RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122 (miR-122), which may suppress the expression of gremlin 2 (GREM2), thus contributing to lipid metabolism disorder. CONCLUSIONS TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.
Animals ; Methylamines/blood* ; Mice ; Psoriasis/chemically induced* ; Lipid Metabolism/drug effects* ; Humans ; Male ; Liver/metabolism* ; Female ; Oxygenases/genetics* ; Disease Models, Animal ; Lipid Metabolism Disorders/etiology* ; Adult ; Mice, Inbred C57BL

The liver performs multiple life-sustaining functions. Hepatic diseases, including hepatitis, cirrhosis, and hepatoma, pose significant health and economic burdens globally. Along with the advances in nanotechnology, mesoporous silica nanoparticles (MSNs) exhibiting diversiform size and shape, distinct morphological properties, and favorable physico-chemical features have become an ideal choice for drug delivery systems and inspire alternative thinking for the management of hepatic diseases. Initially, we introduce the physiological structure of the liver and highlight its intrinsic cell types and correlative functions. Next, we detail the synthesis methods and physicochemical properties of MSNs and their capacity for controlled drug loading and release. Particularly, we discuss the interactions between liver and MSNs with respect to the passive targeting mechanisms of MSNs within the liver by adjusting their particle size, pore diameter, surface charge, hydrophobicity/hydrophilicity, and surface functionalization. Subsequently, we emphasize the role of MSNs in regulating liver pathophysiology, exploring their value in addressing liver pathological states, such as tumors and inflammation, combined with multi-functional designs and intelligent modes to enhance drug targeting and minimize side effects. Lastly, we put forward the problems, challenges, opportunities, as well as clinical translational issues faced by MSNs in the management of liver diseases.

Objective To discuss the factors associated with residual shunt occurring after closure surgery of patent foramen ovale(PFO,and to analyze the relationship between the residual shunt and the relief degree of migraine.Methods A total of 210 patients with PFO,who received closure surgery of PFO due to the occurrence of premonitory migraine at the Jining Municipal First People's Hospital of China from January 2020 to December 2022,were collected.The clinical data,visual analogue scale(VAS)score,and headache impact test-6 questionnaire(HIT-6)score of patients having postoperative residual shunt and patients having no postoperative residual shunt were analyzed.Results A total of 172 patients had no postoperative residual shunt(no-shunt group),and 38 patients had postoperative residual shunt(shunt group).The preoperative PFO width in the shunt group was(1.72±0.34)mm,which was obviously larger than(1.42±0.31)mm in the no-shunt group(P＜0.05).The proportion of patients with right-to-left shunt grades Ⅰ-Ⅱ in resting state in the shunt group was 94.74％,which was higher than 65.21％in the no-shunt group(P＜0.05).No statistically significant differences in gender,age,body mass index(BMI),diabetes,hypertension,hyperlipemia,operation time and occluder type existed between the two groups(P＞0.05).Logistic regression analysis showed that preoperative PFO width and the grade of right-to-left shunt in resting state were the influencing factors for the occurrence of residual shunt(P＜0.05).Based on this model,a column chart model for predicting residual shunt was established,and its predicted area under the ROC curve was 0.882(95％CI:0.731-0.944),the sensitivity was 82.50％,and specificity was 81.00％.The postoperative 12-month VAS score and HIT-6 score in the shunt group were(1.87±0.29)points and(56.02±9.08)points respectively,which were remarkably higher than those in the no-shunt group(P＜0.05).The improvement rates of VAS score and HIT-6 score in the shunt group were(72.59±9.17)％and(22.43±8.11)％respectively,which was lower than those in the no-shunt group(P＜0.05).The postoperative 12-month VAS score and HIT-6 score in the patients having severe residual shunt were(2.21±0.41)points and(61.38±8.45)points respectively,which were higher than those in the patients having mild residual shunt(P＜0.05).The residual shunt volume was negatively correlated with the improvement rates of VAS score and HIT-6 score(r=-0.546 and r=-0.738 respectively,both P＜0.05).Conclusion Residual shunt volume is negatively associated with the relief degree of migraine in patients after receiving closure surgery of PFO due to the occurrence of premonitory migraine.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ+)T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

Objective The aim of this study was to investigate the risk factors for delayed postoperative ileus(PPOI)in colon cancer patients undergoing complete laparoscopic right hemicolectomy combined with intraperitoneal thermal perfusion chemotherapy(HIPEC),and establish a risk prediction model.Methods A retrospective analysis was performed on the case data of 68 colon canc-er patients who underwent complete laparoscopic right hemicolectomy combined with HIPEC at the Department of General Surgery,the First Medical Center of PLA General Hospital from January 2018 to January 2021.The incidence of PPOI was statistically analyzed,and its risk factors were analyzed.A nomogram of risk prediction model was constructed and the effectiveness was verified.Results Among the 83 patients,26 cases(31.3％)developed PPOI.Multivariate logistic regression analysis showed that diabetes(OR=14.820,95％CI:2.819-77.918),previous abdominal surgery(OR=6.514,95％CI:1.433-29.604),preoperative Hb＜9 g/L(OR=5.338,95％CI:1.197-23.809),intraoperative hemorrhage more than 200 mL(OR=4.869,95％CI:1.213-19.544),and not close the mesangial hiatal(OR=5.462,95％CI:1.408-21.186)were the risk factors for PPOI.Based on the results of multiva-riate analysis,a risk prediction model for ROC curve and PPOI nomogram was constructed.The internal validation consistency index(C-index)was 0.85(95％CI:0.735-0.957).Conclusion The risk factors for PPOI after complete laparoscopic right hemicolec-tomy combined with HIPEC are diabetes,previous abdominal surgery,preoperative Hb＜9 g/L,intraoperative hemorrhage more than 200 mL,and failure to close the mesangial hiatal.The constructed nomogram of risk prediction model for PPOI after complete laparo-scopic right hemicolectomy has a good evaluating effect and clinical application value.

ObjectiveTo explore the effect of the serum containing Huanglian Wendantang on pyroptosis in vitro model of insulin resistance and its mechanism. MethodSD rats were randomly divided into two groups， namely Huanglian Wendantang-containing serum group and blank serum group， and given 7.8 g·kg^-1·d^-1 Huanglian Wendantang and equal volume of normal saline by intragastric administration according to body surface area. Blank serum and medicated serum with different concentration were extracted and prepared. HepG2 cells were treated with sodium palmitate to construct the model of insulin resistance （IR）， and they were randomly divided into control group， model group， metformin hydrochloride group， blank serum group， and Huanglian Wendantang-containing serum high-， medium-， and low-dose groups. After 24 h of cultivation， the cells of each group were treated with insulin for 15 min at concentration of 1×10^-7 mol·L^-1， and the cell supernatant was collected. The glucose oxidase （GOD-POD） kit was used to determine the glucose content of each group， and calculate the glucose consumption and inhibition rate. The methyl thiazolyl tetrazolium （MTT） assay was used to detect the cell proliferation， thus screening out the optimal dose of serum containing Huanglian Wendantang. HepG2 cells were randomly divided into control group， model group， and Huanglian Wendantang-containing serum group. The levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in each group were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA and protein expression levels of NOD like receptor protein 3 （NLRP3） in each group were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. In terms of the mechanism， HepG2 cells were randomly divided into control group， empty vector group， NLRP3 overexpression group， empty vector + IR group， empty vector + IR + Huanglian Wendantang-containing serum group， NLRP3 overexpression + IR group， and NLRP3 overexpression + IR + Huanglian Wendantang-contain serum group. GOD-POD method was used to measure the glucose content of each group cells， and calculate the glucose consumption. ELISA was used to determine the release of IL-1β and IL-18 in each group. Real-time PCR and Western blot assay were used to determine the mRNA and protein expressions of cysteinyl aspartate specific proteinase-1 （Caspase-1）， gasdermin D （GSDMD）， and NLRP3. Immunofluorescence assay was used to detect NLRP3， GSDMD， and Caspase -1 expressions. ResultAs compared with the control group， the glucose consumption in the model group was significantly decreased （P<0.01）. As compared with the model group， the increase of the glucose consumption of IR-HepG2 cells was the most significant in the Huanglian Wendantang-containing serum high-dose group （P< 0.01）. As compared with the control group， the IL-1β and IL-18 release levels and the mRNA and protein expressions of NLRP3 in IR-HepG2 cells were significantly increased （P<0.05， P<0.01）. Huanglian Wendantang effectively reduced IR-HepG2 cell supernatant IL-1β， IL-18， and NLRP3 mRNA and protein expressions as compared with the model group （P<0.05， P<0.01）. Overexpression of NLRP3 significantly reduced the cell glucose consumption as compared with the control group and the empty vector group （P<0.01）， and significantly up-regulated the IL-1β and IL-18 levels and the mRNA and protein levels of NLRP3， Caspase-1， and GSDMD as compared with the empty vector + IR group （P<0.05， P<0.01）. Huanglian Wendantang-containing serum effectively reversed the above indicators as compared with the NLRP3 + IR group （P<0.05， P<0.01）. ConclusionHigh fat-induced insulin sensitivity of IR-HepG2 cells is closely related to inflammation and NLRP3 expression. Huanglian Wendantang-containing serum improves IR-HepG2 cell pyroptosis through the targeted inhibition of NLRP3/Caspase-1 signaling pathway， which provides new therapeutic targets for the prevention and treatment of IR and type 2 diabetes mellitus （T2DM）.

Phase separation is an important mechanism that mediates the compartmentalization of proteins in cells. Proteins that can undergo phase separation in cells share certain typical sequence features, like intrinsically disordered regions (IDRs) and multiple modular domains. Sequence-based analysis tools are commonly used in the screening of these proteins. However, current phase separation predictors are mostly designed for IDR-containing proteins, thus inevitably overlook the phase-separating proteins with relatively low IDR content. Features other than amino acid sequence could provide crucial information for identifying possible phase-separating proteins:pro-tein–protein interaction (PPI) networks show multivalent interactions that underlie phase separation process; post-translational modifications (PTMs) are crucial in the regulation of phase separation behavior;spherical structures revealed in immunofluorescence (IF) images indicate condensed dro-plets formed by phase-separating proteins, distinguishing these proteins from non-phase-separating proteins. Here, we summarize the sequence-based tools for predicting phase-separating proteins and highlight the importance of incorporating PPIs, PTMs, and IF images into phase separation prediction in future studies.

OBJECTIVE：To investigate the effects of dexmedetomidine on regional cerebral oxygen saturation and cerebral function in patients undergoing intracranial aneurysm embolization. METHODS ：Totally 44 patients undergoing intracranial aneurysm embolization in the First Affiliated Hospital of Hunan University of TCM during Jun. 2017-Aug. 2019 were collected and randomly divided into group D （22 cases）and group C （22 cases）. Ten minutes before anesthesia induction ，group D was given intravenous injection of Dexmedetomidine hydrochloride injection 1 μg/kg；group C was given buffered normal saline 20 μL. Both groups were induced with Propofol emulsion injection+Midazolam injection+Fentanyl citrate injection+Cisatracurium besylate for injection. During the operation ，group D was given Dexmedetomidine hydrochloride injection 0.5 μg（/ kg·h）+Fentanyl citrate injection+Benzsulfosum atracurium for injection+Propofol emulsion injection to maintain anesthesia ；group C was continuously pumped with buffered normal saline 0.5 μg（/ kg·h）+Fentanyl citrate injection + Benzsulfosum aratracurium for injection Propofol emulsion injection to maintain anesthesia. Before anesthesia induction （T0）， immediately after anesthesia。induction （T1）， 1 min after tracheal intubation （T2）， immediately after operation finished （T3），immediately afte extubation（T4），the mean arterial pressure（MAP），heart rate 中国药房 2021年第32卷第7期 China Pharmacy 2021Vol. 32 No. 7 ·865· （HR），regional cerebral oxygen satur ation（rSO2）were observed in 2 groups. The levels of neuron specific enolase （NSE）and S100 β protein in serum were measured at T1，T3，6 h after operation （T6）. The recovery time ，intraoperative blood loss ， nitroglycerin amount and the occurrence of ADR were recorded. RESULTS ：MAP and HR of group D at T 2-T4 were significantly lower than those at T 0；MAP and HR of group C at T 2-T4 were significantly higher than those at T 0；the group D were significantly lower than the group C at the same period （P＜0.05）；there was no statistical significance in rSO 2 between 2 groups at T 0-T4（P＞ 0.05）. The levels of serum NSE and S 100β protein in 2 groups at T 3 were significantly higher than at T 1；those in 2 groups at T 6 were significantly lower than at T 3，but those of group D were significantly lower than the group C at T 3（P＜0.05）；there was no statistical significance in the levels of serum NSE or S 100β protein between 2 groups at T 1（P＞0.05）. The recovery time of anesthesia，the amount of nitroglycerin ，the incidence of tachycardia ，nausea and vomiting ，restlessness，shivering and cough in group D were significantly shorter or lower than group C （P＜0.05）；there was no statistical significance in the intraoperative blood loss between 2 groups（P＞0.05）. CONCLUSIONS ：Dexmedetomidine can maintain the hemodynamic stability of patients with intracranial aneurysm embolization during the perioperative period ，has little effect on rSO 2 and brain function ，and has good safety.

Objective Through clinical observation and statistics, to get the best curative effect of surgical operation in treating pigment nevus method and provide clinical guidance. Methods We reviewed of face and neck patients (1100 patients) with pigmented nevus in the department in the department of the dermatology,plastic surgery from January 2013 to October 2015, two different methods was designed on each parts and effect of the treatment, especially satisfaction degree was analyzed by statistical methods.Results In 100 cases of patients, only 20 patients had mild scar hyperplasia at the neck incision and the rest of the patients were satisfactory. For special parts such as mouth,nose and eye around,along thedirection of the muscle, arc and along the direction of dermatoglyph incision was designed respectively, patients obtained with higher postoperative satisfaction (P<0.05) . Conclusion In pigmented nevus of face and neck surgery treatment, surgical incision design requires dynamic and static combining method,incision design is important for the postoperative effect and patients' satisfaction.

Objective To compare the clinical effects of intravascular ultrasound (IVUS) and blood flow reserve fraction (FFR) in guiding the treatment of critical disease of coronary artery.Methods Forty nine patients with coronary artery disease who underwent coronary angiography were divided into IVUS group (n=43) and FFR group (n=51).In IVUS group,such as MLA ＜4 mm2 or coronary artery stenosis was insufficient,but IVUS showed unstable plaque,and we went the PCI treatment;in the FFR group,FFR＜0.75 was regarded as coronary stenting sign.The patients were followed up for 6 months.The incidence of cardiovascular adverse events was compared between the two groups.Results (1)There was no significant difference in general information and coronary angiography between the two groups (P＞ 0.05).(2)The proportion of interventional therapy in IVUS group was higher than that in FFR group (P＜0.01).(3)The incidence of adverse events between the two groups was not statistically significant (P＞0.05).Conclusion IVUS and FFR examination can be used to guide the interventional treatment of critical disease of coronary artery.However,the accuracy of IVUS can not replace the status of blood flow reserve.