[Objective] To investigate the functional differences and potential effects of chromatin spatial structure in patients with normal karyotype and complex karyotype multiple myeloma. [Methods] High-throughput chromosome conformational capture (Hi-C) analysis was performed on plasma cells of 1 case with 1q21 complex karyotype and 1 case with normal karyotype multiple myeloma, and the differences in three-dimensional genome structure between the two patients were analyzed, and the transcriptome characteristics of plasma cells were combined to investigate the differential features through gene functional enrichment. [Results] A/B switch occurred in 36% of the chromatin compartments in two cases, and 1 041 genes in patient with complex karyotype had B/A switch. About 3 500 topological association domains (TADs) were identified in each sample, and there was no significant difference. The number of loops identified in complex karyotype sample was 1 069, which was 1/6 of the normal sample, and there were significant differences in the number of three different types of loops, which to some extent reflected the loss of genome stability. Transcriptome analysis showed significant differences in expression profiles between the two patients, and a total of 6 150 differentially expressed genes (3 303 up-regulated genes and 2 847 down-regulated genes) were identified. [Conclusion] Compared with patient with normal karyotype, patient with 1q21 complex karyotype multiple myeloma exhibit significant changes in the spatial structure of plasma cell chromatin at different levels, which leads to changes in gene expression and activation of pathways related to cancer progression.

Jumonji domain-containing protein D3(JMJD3)is a 2-oxoglutarate-dependent dioxygenase that specif-ically removes transcriptional repression marks di-and tri-methylated groups from lysine 27 on histone 3(H3K27me2/3).The erasure of these marks leads to the activation of some associated genes,thereby influencing various biological processes,such as development,differentiation,and immune response.However,comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking.Here,we provide a comprehensive overview of JMJD3,including its structure,functions,and involvement in inflammatory pathways.In addition,we summarize the evidence supporting JMJD3's role in several inflammatory diseases,as well as the potential therapeutic applications of JMJD3 inhibitors.Additionally,we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.

Objective:To investigate the construction and empirical study of the risk predic-tion model of postoperative complications in patients with acute cholecystitis undergoing laparo-scopic cholecystectomy(LC).Method:The clinical data of 101 patients with acute cholecystitis treated by LC from January 2021 to January 2023 were retrospectively analyzed.According to the occurrence of postoperative complications(the following symptoms occurred within 30 days after surgery,such as abdominal hemorrhage,bile leakage,biliary tract injury and wound infection),pa-tients were divided into complication group(26 cases)and non-complication group(75 cases).Uni-variate analysis and multivariate Logistic regression were used to analyze the affecting factors of complications after LC in patients with acute cholecystitis,and the risk prediction model was con-structed,and the predictive value of the model was analyzed by receiver operating characteristic curve(ROC curve).Result:Univariate analysis showed that gender,BMI,cirrhosis,gallstone,gall-bladder atrophy and CCI grade were not correlated with postoperative complications in patients with acute cholecystitis after LC treatment(P＞0.05).Age,gallbladder wall thickness,triangular ana-tomic variation,ASA-PS grade,TG13/TG18 grade were associated with postoperative complica-tions of LC in patients with acute cholecystitis(P＜0.05).Multivariate Logistic regression analysis showed that age＞70 years old,gallbladder wall thickness ≥5mm,triangular anatomical variation,ASA-PS grade Ⅲ～Ⅵ,TG13/TG18 grade Ⅲ were all independent risk factors for postoperative complications(P＜0.05).ROC analysis showed that the AUC of the risk prediction model constructed based on the above five indicators was 0.836,and the sensitivity and specificity were 80.8％and 82.7％,which were all higher than the single indicators in the model,and the degree of fit of the risk prediction model was good(Hosmer-Lemeshow x2=0.998,P=0.986).Conclusion:Age＞70 years old,gallbladder wall thickness ≥5mm,triangular anatomic variation,ASA-PS grade Ⅲ～Ⅵand TG13/TG18 grade Ⅲ were independent risk factors for postoperative complications in patients with acute cholecystitis undergoing LC treatment.The risk prediction model constructed based on the above five indicators has high predictive value for postoperative complications in patients with acute cholecystitis undergoing LC treatment.

AIM To investigate the clinical effects of Xuanfei Jiejing Decoction combined with conventional treatment on patients with asthma of Wind-Phlegm Obstructing Lung Pattern.METHODS One hundred and fifty patients were randomly assigned into control group(75 cases)for 4-week intervention of conventional treatment,and observation group(75 cases)for 4-week intervention of both Xuanfei Jieshi Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,airway inflammatory indices(ECP,IL-4,IgE),lung function indices(FVC,FEV1/FVC,PEF)and putum and mucus indices(4 h sputum volume,sputum viscosity,mucin 5AC)were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,airway inflammatory indices,putum and mucus indices(P＜0.05),and increased lung function indices(P＜0.05),especially for the observation group(P＜0.05).CONCLUSION For the patients with asthma of Wind-Phlegm Obstructing Lung Pattern,Xuanfei Jiejing Decoction combined with conventional treatment can reduce airway inflammatory levels,inhibit airway mucus secretion,improve lung functions,and alleviate clinical symptoms.

Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid decline in renal function. Renal ischemia-reperfusion injury (RIRI) is one of the main causes of AKI with the underlying mechanism incompletely clarified. The liver X receptors (LXRs), including LXRα and LXRβ, are members of the nuclear receptor superfamily. It has been shown that LXRs play an important role in regulating glucose and lipid metabolism, cholesterol efflux, and inflammation. The purpose of this study was to explore the role and mechanism of LXRs in RIRI. We determined the effects of LXR activation on renal function and histological changes in a mouse RIRI model and a cellular model of hypoxia/reoxygenation (H/R). In vivo results showed that LXRs agonist GW3965 significantly inhibited the increase of serum creatinine and urea nitrogen levels induced by RIRI. Both HE and PAS staining of kidney tissues revealed that GW3965 alleviated the morphological damages caused by RIRI. Immunohistochemical staining showed that GW3965 mitigated 4-HNE and GRP78 levels induced by RIRI. Furthermore, TUNEL assay indicated that GW3965 reduced RIRI-induced renal cell apoptosis. Quantitative real-time PCR (qPCR) analysis revealed that GW3965 attenuated RIRI-induced IL-6 and IL-1β mRNA expression. Compared with wild-type group, LXRα gene deficiency had little effect on RIRI-associated renal functional decline and morphological damages. Additionally, in vitro study demonstrated that GW3965 alleviated H/R-induced decrease of HK-2 human renal proximal tubule cell viability and restored the activity of superoxide dismutase (SOD) after H/R. Western blot results showed that GW3965 mitigated the increase of 4-HNE and GRP78 protein expression levels after H/R; However, knockdown of LXRβ using the small interfering RNA (siRNA) technique reduced cell viability compared to GW3965-treated group. Taken together, the LXRs agonist GW3965 significantly alleviates RIRI in mice possibly by reducing apoptosis, oxidative stress, endoplasmic reticulum stress and inflammation. These results also preliminarily confirm that the renal protective effects of LXRs agonists are dependent on LXRβ.
Animals ; Liver X Receptors/genetics* ; Reperfusion Injury/prevention & control* ; Mice ; Benzoates/pharmacology* ; Benzylamines/pharmacology* ; Male ; Endoplasmic Reticulum Chaperone BiP ; Mice, Inbred C57BL ; Apoptosis ; Acute Kidney Injury/prevention & control* ; Kidney/pathology* ; Humans

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Objective: To analyze the treatment and clinical prognosis of lower extremity arterial injury caused by trauma. Methods: The clinical data of 77 patients with traumatic lower extremity arterial injury admitted to Department of Vascular Surgery,Yichang Central People's Hospital from January 2013 to June 2021 were collected retrospectively. There were 65 males and 12 females, with an average age of 47.4 years (range: 7 to 75 years). Among the 77 patients, 56 cases (72.7%) had open injury and 21 cases (27.3%) had closed injury. Iliac artery was injured in 9 cases (11.7%), common femoral artery in 7 cases (9.1%), superficial femoral artery in 1 case (1.3%), popliteal artery in 11 cases (14.3%) and inferior knee artery in 49 cases (63.6%). The treatment methods and clinical effects were analyzed. Results: One case with pelvic fracture combined the internal iliac artery injury and 1 case with multiple injuries involving the common femoral artery died of circulatory failure before surgery. Seventy-five cases received vascular-related operations, including arterial ligation in 24 cases, arterial reconstruction in 40 cases, stent graft implantation in 1 case, primary amputation in 2 cases, and arterial embolization in 8 cases. The overall mortality rate was 6.5% (5/77), all of which were closed injuries. Except for 2 cases who died before surgery, 3 cases with pelvic fracture combined the internal iliac artery injury died of multiple organ failure after internal iliac artery embolization. There were 8 cases received amputation (10.4%, 8/77), 5 cases with closed injury and 3 cases with open injury. In addition to 2 cases with primary amputation, 6 cases underwent secondary amputation due to ischemia-reperfusion injury after revascularization (4 cases with popliteal artery injury and 2 cases with subpatellar artery injury). The average followed-up time was 17 months (range: 2 months to 8 years). One patient with femoral artery injury underwent autologous great saphenous vein bypass, and lower limb artery CT angiography was re-examined 6 months after the operation, and 30% distal anastomotic stenosis was found. Ankle brachial index<0.8 was found in two patients 1 year after popliteal artery repair, but none of the patients had intermittent claudication symptoms, and no further intervention was performed. Five patients suffered delayed healing due to severe lower limb injury, fracture and skin injury. Among them, 2 cases had poor wound healing at the stump of amputation, which gradually healed 3 to 5 months after several debridements. The other 3 vascular injury combined with tibial fracture patients had delayed tibial healing after surgery, but no symptoms of vascular ischemia occurred. All the other patients recovered well and no other serious complications occurred. Conclusions: The proportion of death and disability in patients with lower limb artery injury caused by trauma is high. Active and orderly surgical repair according to the site and type of injury can reduce the mortality, save the function of the affected limb, and promote the healing of injury.
Amputation ; Female ; Femoral Artery ; Humans ; Lower Extremity ; Male ; Middle Aged ; Popliteal Artery/surgery* ; Retrospective Studies ; Treatment Outcome ; Vascular System Injuries/surgery*

Aim To evaluate the protective effect of α-asarone on microglials with cerebral ischemia/reperfusion injury by measuring the expression of polar transformation and related inflammatory proteins in BV2 cells in vitro and its mechanisms.Methods The cerebral ischemia/reperfusion injury BV2 cells were pretreated by α-asarone in vitro and simulated by OGD/R model.The effect of α-asarone on the viability of damaged cells in OGD/R model was determined by CCK-8; the morphological changes of cells were observed to analyze the general morphology of cells; the levels of proinflammatory factor IL-1β, IL-18 and anti-inflammatory factor IL-10, IL-4, and ROS activity secreted by BV2 cells were detected by ELISA; the protein expressions of TGF-β, TNF-α and inflammatory related protein NLRP3, caspase 1, p-NF-κB were detected by Western blot.Results The results of in vitro experiments were as follows: the activity of damaged cells in OGD/R model was significantly increased by α-asarone, with the increase of administration dose, the cells in the low, medium and high dose groups of α-asarone decreased, and the "amoeba-like" cells and the cell body were gradually became stereoscopic and full.From the results of cell morphology, it could be seen that α-asarone had a certain proliferative effect on normal cells; the release was significantly reduced of proinflammatory factor IL-1β, IL-18 and TNF-α in OGD/R injured BV2 cells pretreated with α-asarone, also increased the release of IL-10, IL-4 and TGF-β, with a dose-effect relationship, and the high dose(16 μmol·L-1)was the best; the expressions of inflammatory related protein NLRP3, caspase 1, NF-κB and ROS activity in injured cells of OGD/R model were significantly reduced after pretreatment with α-asarone.Conclusions α-asarone has a significant protective effect on cerebral ischemia/reperfusion injury, mainly by regulating ROS activity and inhibiting phosphorylation of NF-κB, in order to reduce the excessive activation of NLRP3 inflammatory corpuscles reducing the secretion of proinflammatory factor IL-1β and IL-18, promoting the secretion of anti-inflammatory factor IL-10 and IL-4, so as to protect cerebral ischemia/reperfusion injury by anti-inflammatory reaction.

Farnesoid X receptor (FXR) has been identified as an inhibitor of platelet function and an inducer of fibrinogen protein complex. However, the regulatory mechanism of FXR in hemostatic system remains incompletely understood. In this study, we aimed to investigate the functions of FXR in regulating antithrombin III (AT III). C57BL/6 mice and FXR knockout (FXR KO) mice were treated with or without GW4064 (30 mg/kg per day). FXR activation significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), lowered activity of activated factor X (FXa) and concentrations of thrombin-antithrombin complex (TAT) and activated factor II (FIIa), and increased level of AT III, whereas all of these effects were markedly reversed in FXR KO mice. In vivo, hepatic AT III mRNA and protein expression levels were up-regulated in wild-type mice after FXR activation, but down-regulated in FXR KO mice. In vitro study showed that FXR activation induced, while FXR knockdown inhibited, AT III expression in mouse primary hepatocytes. The luciferase assay and ChIP assay revealed that FXR can bind to the promoter region of AT III gene where FXR activation increased AT III transcription. These results suggest FXR activation inhibits coagulation process via inducing hepatic AT III expression in mice. The present study reveals a new role of FXR in hemostatic homeostasis and indicates that FXR might act as a potential therapeutic target for diseases related to hypercoagulation.
Animals ; Antithrombin III ; Blood Coagulation ; Hepatocytes ; Liver ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Cytoplasmic and Nuclear/genetics*

OBJECTIVE: To analyze the clinical data of patients undergoing intravenous sedation in oral and maxillofacial surgery, to understand the epidemiological characteristics, to evaluate the efficacy and safety of intravenous sedation for oral surgery, and to summarize our experience. METHODS: We retrospectively reviewed the clinical data of patients undergoing intravenous sedation between January 2010 and December 2018 in the Department of Oral and Maxillofacial Surgery, Peking University School of Stomatology. The gender, age, source, disease types, the values of perioperative vital signs, the use of sedatives and analgesics, duration of surgery and sedation, effect of sedation during the operation and the postoperative anterograde amnesia were analyzed. RESULTS: A total of 2 582 patients experienced oral surgery by intravenous sedation. The peak age was 3.5 to 10 years and between 21 to 40 years. Supernumerary teeth (38%, 981/2 582) and impacted third molars (30%, 775/2 582) were the major disease types, and other types of disease accounted for 32 percent (826/2 582). The values of heart rate(HR), mean arterial pressure(MAP), respiration rate(RR) and bispectral index(BIS) showed statistically significant differences at the time of before sedation, local anesthesia injection, surgical incision, 10 min after operation and the end of operation. In the study, 69%(1 781/2 582) cases received midazolam alone, 7%(181/2 582) cases received propofol alone, and 24% (620/2 582) cases received midazolam and propofol combined for intravenous sedation. Fentanyl (33%, 852/2 582)was the most common intravenous analgesic we used, followed by flurbiprofen axetil (23%, 594/2 582) and ketorolac tromethamine (6%, 157/2 582). Besides, 35% (907/2 582) patients didn't use any intravenous analgesic during the surgery. The average operation time was (31.2±20.8) min, and the average sedation time was (38.4±19.2) min. During the surgery procedure, most of the patients scored on a scale of 2 to 4 according to the Ramsay sedation score (RSS). The postoperative anterograde amnesia rates of local anesthesia injection, surgical incision and dental drill during surgery were 94% (2 431/2 582), 92% (2 375/2 582) and 75% (1 452/1 936). CONCLUSION Intravenous sedation on the oral and maxillofacial surgery is effective and safe, can make the patients more comfortable, and should be further promoted and applied.
Anesthesia, Dental ; Anesthetics, Intravenous ; Humans ; Hypnotics and Sedatives ; Midazolam ; Propofol ; Retrospective Studies ; Surgery, Oral