Renal ischemia-reperfusion injury （RIRI） is a major cause of acute kidney injury during kidney transplantation and peri-operative settings， and there is still a lack of safe and effective targeted preventive and therapeutic drugs in clinical practice. Specifically， xanthohumol， luteolin， dracorhodin C， naringin， senkyunolide Ⅰ， verbascoside， and shikonin enhance antioxidant defenses， and inhibit lipid peroxidation and ferroptosis via the nuclear factor-erythroid 2-related factor 2/heme oxygenase-1 pathway. Apigenin， nobiletin， tanshinone Ⅱ A ， and salidroside activate the phosphatidylinositol 3-kinase/protein kinase B pathway to inhibit mitochondria- dependent apoptosis and facilitate renal repair. Quercetin， methyleugenol， cyanidin-3-glucoside， and platycodin D promote autophagy and improve mitochondrial homeostasis through the adenosine monophosphate-activated protein kinase（AMPK）/mTOR or AMPK/phosphatase and tensin homolog-induced kinase 1/Parkin pathways. In addition， hesperidin， curcumin， ganoderic acid， pulsatilla saponin B4， capsaicin， and diosgenin mitigate inflammatory responses and decrease renal tubular injury markers by inhibiting the Toll-like receptor 4/nuclear factor κB， high mobility group box 1， Janus kinase/signal transducer and activator of transcription pathways， thereby exerting multi-target， multi-stage renoprotective effects.

BACKGROUND: Angiotensin receptor neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) are the cornerstones in treating heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are included in HFrEF treatment guidelines. However, the effect of SGLT-2i and the five drugs on HFrEF have not yet been systematically evaluated. METHODS: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) from inception dates to September 23, 2022. Additional trials from previous relevant reviews and references were also included. The primary outcomes were changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter/dimension (LVEDD), left ventricular end-systolic diameter/dimension (LVESD), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI). Secondary outcomes were New York Heart Association (NYHA) class, 6-min walking distance (6MWD), B-type natriuretic peptide (BNP) level, and N-terminal pro-BNP (NT-proBNP) level. The effect sizes were presented as the mean difference (MD) with 95% confidence interval (CI). RESULTS: We included 68 RCTs involving 16,425 patients. Compared with placebo, ARNI + BB + MRA + SGLT-2i was the most effective combination to improve LVEF (15.63%, 95% CI: 9.91% to 21.68%). ARNI + BB + MRA + SGLT-2i (5.83%, 95% CI: 0.53% to 11.14%) and ARNI + BB + MRA (3.83%, 95% CI: 0.72% to 6.90%) were superior to the traditional golden triangle ACEI + BB + MRA in improving LVEF. ACEI + BB + MRA + SGLT-2i was better than ACEI + BB + MRA (-8.05 mL/m 2 , 95% CI: -14.88 to -1.23 mL/m 2 ) and ACEI + BB + SGLT-2i (-18.94 mL/m 2 , 95% CI: -36.97 to -0.61 mL/m 2 ) in improving LVEDVI. ACEI + BB + MRA + SGLT-2i (-3254.21 pg/mL, 95% CI: -6242.19 to -560.47 pg/mL) was superior to ARB + BB + MRA in reducing NT-proBNP. CONCLUSIONS: Adding SGLT-2i to ARNI/ACEI + BB + MRA is beneficial for reversing cardiac remodeling. The new quadruple drug "ARNI + BB + MRA + SGLT-2i" is superior to the golden triangle "ACEI + BB + MRA" in improving LVEF. REGISTRATION PROSPERO; No. CRD42022354792.
Humans ; Heart Failure/physiopathology* ; Stroke Volume/physiology* ; Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use* ; Randomized Controlled Trials as Topic ; Mineralocorticoid Receptor Antagonists/therapeutic use* ; Adrenergic beta-Antagonists/therapeutic use*

The interplay between psychological pain and physical pain is one of the key issues in the research of non-suicidal self-injury (NSSI). Psychological pain, driven by negative self-perception and difficulties in emotional regulation, activates specific brain regions, such as the anterior cingulate gyrus and insula, areas that overlap with neural networks involved in physical pain. Physical pain can, in turn, activate distinct neural pathways that temporarily alleviate psychological pain. However, repeated self-injury may lead to increased pain tolerance over time, contributing to a vicious cycle. This paper reviews the potential neural network connections and interactions between psychological and physical pain in the context of NSSI behavior. It also summarizes current clinical interventions and their effectiveness in treating NSSI, aiming to offer new insights for future research and clinical practice in preventing and treating NSSI.

Hepatic osteodystrophy is a common complication in patients with chronic liver disease and is influenced by various risk factors， and it has become one of the important influencing factors for the prognosis of liver transplantation. By analyzing the influencing factors for bone health and bone metabolism during the perioperative period of liver transplantation， this article emphasizes the importance of a comprehensive assessment of bone health and necessary interventions at this stage， with an aim to reduce the risk of postoperative complications and improve the long-term prognosis of patients. A deeper exploration of the association between hepatic osteodystrophy and the prognosis of liver transplantation can help to reveal the key influencing factors for postoperative outcomes， thus providing a theoretical basis for optimizing postoperative management strategies. Furthermore， advances in this research field will offer new insights into the treatment of patients receiving liver transplantation， and it is expected to further improve quality of life and long-term survival rate.

Objective To investigate the effects of artesunate(Art)on the proliferation,apoptosis,and autophagy of nephroblastoma cell line(SK-NEP-1).Methods SK-NEP-1 cells were intervened with different concentrations of Art(0,10,20,40 and 80 μmol/L),and MTT method was applied to calculate the cell proliferation inhibition rate to screen the optimal intervention concentration;SK-NEP-1 cells were separated into control group,Art group,3-MA group(Art+autophagy inhibitor,3-methyladenine),and Rapa group(Art+autophagy activator rapamycin).EdU and flow cytometry were applied to detect cell proliferation and apoptosis,respectively;MDC staining was applied to detect autophagy in cells;the level of reactive oxygen species(ROS)in cells was detected by DCFH-DA fluorescent probe;the expression of proliferating cell nuclear antigen(PCNA),anti apoptotic factor B cell lym-phomatoma-2(Bcl-2),Bcl-2 associated X protein(Bax),microtubule junction protein 1 light chain 3 Ⅱ/3 Ⅰ(LC3 Ⅱ/LC3 Ⅰ),selective autophagy junction protein 1(p62),and benzyl chloride 1(Beclin-1)proteins in cells were detected by Western blot.Results Compared with 0 μmol/L Art,the proliferation inhibition rate of SK-NEP-1 cells was gradually increased after 10,20,40 and 80 μmol/L Art treatment(P＜0.05),and the IC50 value was 46.881 μmol/L,so 40 μmol/L Art was selected for follow-up experiments.Compared with the control group,the apoptosis rate,relative autophagy fluorescence intensity,ROS level,Bax,LC3 Ⅱ/LC3 Ⅰ,Beclin-1,PINK1,and Parkin protein expression levels of SK-NEP-1 cells in the Art group were obviously increased,the EdU positive cell rate,PCNA,Bcl-2,and P62 protein expression levels were obviously reduced(P＜0.05);The auto-phagy inhibitor 3-MA inhibited the promoting effect of Art on apoptosis and autophagy of nephroblastoma cells and inhibit proliferation(P＜0.05).Conclusions Art inhibits the proliferation of nephroblastoma cell line SK-NEP-1,and promotes autophagy and apoptosis.

Objective:To explore differences in the clinical and pathological features and postoperative survival after radical resection of biliary tract cancer in different locations such as intrahepatic cholangiocarcinoma,perihilar cholangiocarcinoma,distal cholangiocarcinoma,and gallbladder cancer.Methods:This is a retrospective case series study. The clinical and pathological data of 4 852 patients with biliary tract cancer admitted to the Department of Hepatobiliary Surgery,the First Affiliated Hospital of Xi ′an Jiaotong University from January 2013 to December 2022 were retrospectively analyzed. Among them, 2 110(43.49%%) patients were male and 2 742(56.51%) patients were female,aged from 26 to 88 years with age of (61.3±10.8) years. Observation indicators: (1) The distribution,diagnosis and treatment of patients with biliary tract cancer; (2) Comparison of clinical and pathological features of patients with biliary tract cancer after curative-intent resection; (3) Survival analysis of patients with biliary tract cancer after curative-intent resection; (4) Analysis of effect on adjuvant therapy for patients with biliary tract cancer after curative-intent resection. One-way analysis of variance,Kruskal-Wallis H test and χ 2 test were used for among-group comparisons,respectively. Survival univariate analysis was performed using the Kaplan-Meier method and Log-rank test. Results:Among the 4 852 patients with biliary tract cancer,there were 2 303 cases (47.46%) of gallbladder cancer,952 cases (19.62%) of intrahepatic cholangiocarcinoma,892 cases (18.38%) of perihilar cholangiocarcinoma,and 705 cases(14.53%) of distal cholangiocarcinoma. From the perspective of the year of diagnosis and treatment,the overall number of patients diagnosed and treated for biliary tract cancer has shown an upward trend. From the perspective of diagnosis and treatment,the curative-intent resection rate was 33.37%(1 619/4 852),and the curative-intent resection rate of distal cholangiocarcinoma was higher than that of other biliary tract cancer ( χ2=23.897, P<0.01). Univariate analysis showed that there were statistical differences in gender,age,bile duct stones,total bilirubin at admission,carcinoembryonic antigen,CA19-9,CA125,the degree of pathological differentiation,vascular invasion,microvascular invasion,perineural invasion,surgical margins,pT staging,and pN staging among patients for biliary tract cancer in different locations (all P<0.05). Survival comparison analysis showed that recurrence-free survival and overall survival of patients with gallbladder cancer after curative-intent resection were significantly better than those of intrahepatic cholangiocarcinoma,perihilar cholangiocarcinoma,and distal cholangiocarcinoma ( χ 2=87.780,83.717,both P<0.01). Comparing the postoperative prognosis of patients with biliary tract cancer between the two periods of 2013 to 2017 and 2018 to 2022, the results showed that recurrence-free survival and overall survival of patients with biliary tract cancer from 2018 to 2022 were significantly better than those from 2013 to 2017 ( χ 2=31.202,25.615, both P<0.01),and the proportion of early recurrence and short-term death after curative-intent resection was significantly reduced ( χ 2=21.588,9.623, both P<0.01),with gallbladder cancer being the most significant ( P<0.01). Postoperative adjuvant therapy for patients with biliary tract cancer can effectively prolong recurrence-free survival and overall survival ( χ 2=5.033,11.273,both P<0.05). Conclusions:Gallbladder cancer remains the most common biliary tract cancer with a relatively favorable prognosis after radical resection. There are significant differences in the clinical and pathological features of biliary tract cancer in different locations,and patients with adjuvant therapy effectively improving prognosis.

BACKGROUND:Long non-coding RNA(LncRNA)plays an important role in nervous system development and neurological diseases.Previous studies by the research team have demonstrated that human umbilical cord mesenchymal stem cells overexpressing erythropoietin(EPO-MSCs)under ischemic and hypoxic conditions have better neuroprotective functions and significantly activate the expression of LncRNA XIST.Research suggests that XIST is related to the pathogenesis of hypoxic-ischemic encephalopathy,but the role and mechanism of its regulation by EPO-MSCs in protecting ischemic-hypoxic neurons remain unclear.OBJECTIVE:To explore the new mechanism by which LncRNA XIST,in response to EPO-MSC signaling,affects the apoptosis of ischemic-hypoxic SH-SY5Y cells.METHODS:(1)SH-SY5Y cell lines with knockdown of LncRNA XIST(sh-XIST)and negative control(NC-XIST)were constructed through lentiviral transfection.Oxygen-glucose deprivation was used to induce ischemic-hypoxic injury in the cells.Transwell chambers were used to create a non-contact co-culture system with EPO-MSCs,sh-XIST,and NC-XIST ischemic-hypoxic SH-SY5Y cells.Cell proliferation ability was detected using the CCK-8 assay.Cell migration ability was assessed using the scratch assay,and cell apoptosis was measured by flow cytometry.(2)RNA-seq bioinformatics analysis was performed to screen for differentially expressed genes and pathways between sh-XIST and NC-XIST cell lines.Dual-luciferase experiments were used to verify the relationship between miR-124-3p and the target genes XIST and GRIN1.qRT-PCR was conducted to validate the expression levels of downstream miR-124-3p and GRIN1 genes.(3)miR-124-3p inhibitors and mimics were added to verify phenotypic changes in SH-SY5Y cells after ischemic-hypoxic injury and co-culture with EPO-MSCs.RESULTS AND CONCLUSION:(1)Compared with the NC-XIST group,SH-SY5Y cells in the sh-XIST group showed reduced proliferation and migration abilities and increased apoptosis after ischemic-hypoxic injury and co-culture with EPO-MSCs.(2)Dual-luciferase experiments showed that miR-124-3p interacted with the target gene XIST.SH-SY5Y cells transfected with miR-124-3p mimics and co-cultured with EPO-MSCs showed decreased apoptosis after ischemic-hypoxic injury,while SH-SY5Y cells transfected with miR-124-3p inhibitors showed increased apoptosis after co-culture with EPO-MSCs.(3)Transcriptomic sequencing and bioinformatics analysis of sh-XIST revealed significant downregulation of the neuroactive ligand-receptor pathway and the key receptor gene GRIN1 for central nervous system development.(4)Dual-luciferase experiments showed that miR-124-3p interacted with GRIN1.GRIN1 expression was significantly downregulated in the sh-XIST group after ischemic-hypoxic injury compared with the NC-XIST group.These findings indicate that LncRNA XIST promotes GRIN1 expression by upregulating miR-124-3p,thereby reducing cell apoptosis after ischemic-hypoxic injury and co-culture with EPO-MSCs and enhancing proliferation and migration.sh-XIST can block this protective function.

A 42-year-old male patient developed mild allergic symptoms after the use of cisatracurium besylate in laparoscopic left renal tumor resection,which was relieved by symptomatic treatment.When the drug was added again intraoperatively,the patient's blood pressure decreased sharply from 120/71 mmHg to 50/30 mmHg,and the airway resistance increased from 16 cmH2O to 38 cmH2O,and the patient developed typical signs of anaphylactic shock.After immediate intravenous injection of epinephrine,calcium chloride and other drugs,the patient's blood pressure rose to 95/57 mmHg,airway resistance decreased to 20 cmH2O,and vital signs tended to be stable.The Naranjo's Assessment Scale was used to evaluate and analyze the correlation of suspected drugs.The score was 9 points,indicating that the association between anaphylactic shock and cisatracurium besylate in this patient was judged to be"definitely related".This article suggests that cisatracurium besylate carries an allergic risk and should be used with caution,and the monitoring of vital signs and allergic reactions should be strengthened for early identification and timely treatment to ensure the safety of patients during the perioperative period.

Objective:To identify prognostic factors associated with survival rates in patients with distal cholangiocarcinoma after radical surgery, and to construct a Nomogram prediction model based on these factors, as well as to perform internal validation of the model.Methods:A retrospective study was conducted on the clinical data of 162 patients (76 males and 86 females) with distal cholangiocarcinoma who underwent radical surgery at the Department of Hepatobiliary Surgery, Ningxia Medical University General Hospital from January 2011 to July 2019. The study used univariate and multivariate Cox regression analysis to identify independent risk factors and constructed a Nomogram prediction model using R software version 4.4.1. Additionally, the predictive accuracy of the model was evaluated through the C-index, the area under the receiver operating characteristic curve, and the calibration curve.Results:The median overall survival for the 162 patients was 18.4 months. The final multivariate Cox regression analysis revealed that the following factors were independent risk factors for poor postoperative prognosis in patients with distal cholangiocarcinoma: patient age [> 60 years, P = 0.004, hazard ratios ( HR) = 1.876], tumor diameter (> 2.0 cm, P < 0.001, HR = 0.174), tumor differentiation degree [moderately differentiated/moderately to highly differentiated/highly differentiated, P = 0.017, HR = 1.407], lymph node metastasis (Yes, P = 0.002, HR = 0.551), and vascular invasion (Yes, P = 0.025, HR = 1.329) (all P < 0.05). Based on these independent risk factors identified through statistical analysis, the C-index of the constructed nomogram prediction model was 0.793. The area under the receiver operating characteristic curve values for the model predicting postoperative 1-year, 3-year, and 5-year overall survival rates were 0.932, 0.771, and 0.758,respectively. Conclusions:Patient age, tumor diameter, tumor differentiation degree, lymph node metastasis, and vascular invasion are independent risk factors for poor postoperative prognosis in patients with distal cholangiocarcinoma. The final Nomogram prediction model demonstrates good predictive ability and has certain practical application potential.