Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective To construct a symptom network in patients with acute type A aortic dissection(ATAAD),so as to provide theoretical basis for the screening of dissection ATAAD during emergency pre-screening triage.Methods There were 433 patients diagnosed with ATAAD during 2019 to 2023 in an emergency department of a tertiary hospital in Wuhan.Their basic information and medical records were reviewed by self-designed data questionnaire.UCINET6.0 software was used to construct a symptom network,analyze the centrality index and determine the core symptoms.Symptom distribution of patients with positive and negative blood pressure in extremities was analyzed in the further.Results The most common symptoms in patients with type A aortic dissection were chest pain(77.37％),back pain(42.96％),and sweating(29.79％).In the symptom network,chest pain had the highest degree(rs=659).The closeness of chest pain,chest tightness,shortness of breath,back pain,nausea and vomiting,limb numbness and fatigue were same(rc=93.33).Fatigue has the highest betweenness(rb=13.69).Patients with positive limbs blood pressure mainly reported chest pain(70.17％),back pain(44.96％),and nausea and vomiting(19.33％),while those with negative limb blood pressure mainly reported chest pain(63.64％),back pain(63.64％),and orosphyalgia(39.40％).Orosphyalgia had the highest degree(rs=20).Conclusion The symptoms of ATAAD are complex and varied in patients.During triage,nurses should measure the limb blood pressure when patients complained chest pain alone or when combined with other hypoperfusion symptoms,such as back pain,chest tightness,sweating,near-death sensation,and shortness of breath.Aortic dissection cannot be ruled out in patients with negative blood pressure when they had chest pain,back pain or orosphyalgia.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Objective To evaluate postoperative recovery and health-related quality of life in patients undergoing robotic,laparoscopic,or open total hysterectomy.Methods A total of 152 patients who underwent total hysterectomy at the Department of Obstetrics and Gynecology of The Second Affiliated Hospital of Naval Medical University from May 2022 to May 2024 were enrolled and assigned to robot-assisted laparoscopic surgery group(robotic surgery group,44 cases),traditional laparoscopic surgery group(laparoscopic surgery group,62 cases),or open surgery group(46 cases)based on the surgical approach.General information,perioperative indexes,and discomfort symptoms 1 month after discharge were collected.Health-related quality of life was evaluated using 36-item short-form health survey(SF-36)at 1-month postoperative follow-up.Results There were no significant differences in age,body mass index,education level,work status,or diagnosis of benign or malignant diseases(all P＞0.05).The postoperative hospital stay,time of first ambulation,time of first oral intake,and 24-h pain score in the robotic surgery group were significantly lower than those in the laparoscopic and open surgery groups(all P＜0.01).The incidence of urinary system and digestive system discomfort within 1 month after discharge was significantly lower in the robotic surgery group than in the laparoscopic and open surgery groups,and the incidence of lower abdominal pain was significantly lower in the robotic surgery group than in the open surgery group(all P＜0.01).The scores of SF-36 in each dimension were significantly higher in the robotic surgery group than those in the laparoscopic and open surgery groups 1 month after discharge(all P＜0.01).Conclusion Compared with those undergoing traditional laparoscopic or open total hysterectomy,patients who underwent robot-assisted laparoscopic total hysterectomy demonstrate faster postoperative recovery and better health-related quality of life.

Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective·To evaluate the detection efficacy and clinical value of non-invasive prenatal testing(NIPT)for identifying copy number variations(CNVs)in the recurrent 17p12 region,including the peripheral myelin protein 22(PMP22)gene.Methods·Pregnant women who underwent NIPT in the International Peace Maternity & Child Health Hospital,Shanghai Jiao Tong University School of Medicine between July 2020 and April 2024 were enrolled.Clinical data of individuals indicated as high-risk for microdeletions/duplications in the 17p12 region based on NIPT results were collected.Follow-up was conducted to assess the results of subsequent prenatal diagnosis and chromosomal microarray analysis(CMA)performed on peripheral blood from both the pregnant women and their husband.The positive predictive value(PPV)of NIPT for detecting microdeletions/duplications in the 17p 12 region,as well as the underlying causes of false positives,was analyzed.Pregnancy outcomes and related clinical phenotypes of fetuses and pregnant women diagnosed with 17p12 CNVs were followed up.Results·A total of 61 858 pregnant women underwent NIPT testing.NIPT identified 24 cases(0.04％)as high-risk for CNVs in the 17p12 region,including six cases of high-risk 17p12 microduplication and 18 cases of high-risk 17p12 microdeletion.All 24 pregnant women received genetic counseling,and 21(87.50％)underwent invasive prenatal diagnosis.Invasive prenatal diagnostic confirmed four fetuses with 17p12 microduplications,nine fetuses with 17p12 microdeletions,and eight fetuses with no abnormalities,yielding a PPV of 61.90％(13/21).CMA analysis of maternal peripheral blood in the eight false-positive cases revealed that all mothers carried 17p12 CNVs.Further analysis of pregnant women with NIPT-indicated maternal CNVs revealed that all of them carried relevant CNVs.Among the 20 women with successful follow-up,the majority had normal deliveries,with only one case choosing to terminate the pregnancy due to a de-novo fetal 17p12 microduplication.Normally delivered fetuses(average age:1.5 years)were followed up without reporting any significant abnormalities.Of the 16 pregnant women carrying 17p12 CNVs,only two exhibited clinical phenotypes associated with these CNVs,while the others remained asymptomatic.Conclusion·NIPT demonstrates favorable detection efficacy for CNVs in the 17p12 region.Maternal CNVs are the primary cause of false-positive NIPT results for this region.

Objective:To discuss the correlation of International Society of Urological Pathology (ISUP) pathological grading with 18F-prostate specific membrane antigen (PSMA)-1007 positron emission tomography-computed tomography (PET/CT) parameters and serum total prostate specific antigen (tPSA) in prostate cancer, and assess the clinical value of PET/CT combined with tPSA in predicting the ISUP pathological grade of prostate cancer. Methods:The correlation of ISUP pathological grade with primary parameters of PET/CT images and serum tPSA of 117 patients diagnosed with prostate cancer at Shanxi Cancer Hospital from August 2018 to February 2023 and taken 18F-PSMA-1007 PET/CT imaging were retrospectively analyzed. Univariate and multivariate logistic regressions were used to identify the independent influencing factors for ISUP pathological grading of prostate cancer. The receiver operating characteristic (ROC) curves were used to predict the efficacy between the high and low ISUP grades for prostate cancer. Results:Of the 117 patients, 20 were in ISUP Group 1, 25 in Group 2, 18 in Group 3, 32 in Group 4, and 22 in Group 5. Of these, 63 were in the low-grade group (Groups 1-3) and 54 were in the high-grade group (Groups 4-5). The tumor long diameter was 3.10 (2.05, 4.25) cm, the prostate volume was 40.11 (33.13, 51.85) cm 3, the serum tPSA was 19.71 (12.25, 42.83) ng/ml, the prostate specific antigen density (PSAD) was 0.51 (0.31, 1.01) ng·ml -1·cm -3, the maximum standard uptake value of the lesion (SUVmax) was 15.24 (10.87, 22.03), and the tumor/spleen uptake ratio (TSR) was 1.61 (1.08, 2.15) in the 117 patients. The correlation analysis displayed that the SUVmax, TSR, and tPSA were positively correlated with ISUP groups ( r=0.640, 0.619, and 0.500, P＜0.01). The differences among SUVmax, TSR, long diameter, tPSA, and PSAD were statistically significant when compared among the five ISUP groups ( H=48.98, 45.63, 26.82, 33.95, and 23.81, P＜0.001). The differencesin serum tPSA ( z=5.19), PSAD ( z=4.64), long diameter ( z=3.19), SUVmax ( z=5.57), and TSR ( z=5.53) of the patients between the low-grade group and the high-grade group were statistically significant ( P＜0.01). In multivariate analysis, TSR ( OR=4.172, 95% CI: 2.095-8.308, P＜0.001) and the serum tPSA ( OR=1.042, 95% CI: 1.014-1.070, P＜0.01) were independent influencing factors for ISUP grades. ROC analysis revealed that the area under the curve for the 18F-PSMA-1007 PET/CT parameters SUVmax and TSR to predict low- or high-grade ISUP for prostate cancer was 0.800 (95% CI: 0.717-0.883) and 0.797 (95% CI: 0.713-0.881), respectively. Among the 70 patients who underwent radical prostatectomy, the postoperative recurrence rate of high-grade ISUP patients was higher than that of low-grade patients (54.8% and 25.6%, χ 2=6.21, P＜0.05). Conclusions:18F-PSMA-1007 PET/CT has good application in predicting ISUP grading of prostate cancer. TSR and the serum tPSA are independent predictors for the pathological grade.

Objective:To evaluate the role of necroptosis in paclitaxel-induced cognitive dysfunction in mice.Methods:Thirty SPF healthy male C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=10 each) using a random number table method: vehicle control group (Veh group), paclitaxel group (PTX group), and paclitaxel+ a specific inhibitor of necroptosis Necrostatin-1 group (P+ N group). In PTX group and P+ N group, paclitaxel 10 mg/kg (diluted to 5 mg/ml in anhydrous ethanol and castor oil [1∶1], and further diluted to 1 mg/ml in 0.9% normal saline before use) was intraperitoneally injected daily for 7 consecutive days to induce cognitive dysfunction. P+ N group received an intraperitoneal injection of Necrostatin-1 6.5 mg/kg (diluted to 10 mg/ml in dimethyl sulfoxide, and further diluted to 1 mg/ml in 0.9% normal saline before use) at 2 h before paclitaxel administration every other day, 4 times in total. Veh group received the equal volume of solvent at the matched time points as previously described in P+ N group. After establishment of the model, spontaneous locomotor activity was assessed using the open field test, followed by the novel object recognition test and the Morris water maze to evaluate the cognitive function. The animals were sacrificed after the end of the Morris water maze test, and the hippocampal tissues were collected for determination of the expression of necroptosis-related proteins receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3, mixed lineage kinase domain-like protein (MLKL), and phospho-MLKL (p-MLKL) (by Western blot analysis) and contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) (double immunofluorescence staining) and for observation of the localization of programmed necrosis cells (using enzyme-linked immunosorbent assay). Results:There were no significant differences in the total distance traveled and mean movement speed in the open field test or swimming speed in the Morris water maze test among the three groups ( P>0.05). Compared to Veh group, the time spent in the central zone in the open field and time spent in the original platform quadrant were significantly shortened, the discrimination index was decreased, the escape latency was prolonged, the number of crossing the original platform was reduced, the expression of RIPK1, RIPK3, MLKL and p-MLKL was up-regulated, the contents of TNF-α and IL-1β were increased, and the number of RIPK1-positive neurons was increased in PTX group ( P<0.05). Compared to PTX group, the time spent in the central zone in the open field test and time spent in the original platform quadrant were significantly prolonged, the discrimination index was increased, the escape latency was shortened, the number of crossing the original platform was increased, the expression of RIPK1, RIPK3, MLKL and p-MLKL was down-regulated, the contents of TNF-α and IL-1β were decreased, and the number of RIPK1-positive neurons was decreased in P+ N group ( P<0.05). Conclusions:Necroptosis in hippocampal neurons can lead to neuroinflammation, thus contributeing to paclitaxel-induced cognitive dysfunction in mice.

Objective : To analyze the mediating effect of psychological resilience between occupational stress and job burnout of medical staff, so as to provide the reference for improving job burnout of medical staff. Methods: The front-line medical staff from four tertiary general hospitals in a joint logistics support center were selected as the research objects from April to June 2022 using the convenience sampling method. The data on gender, age, professional title, and working years were collected by a questionnaire survey. Occupational stress, psychological resilience, and job burnout were evaluated using the Job Stressors Scale, the Connor-Davidson Resilience Scale, and the Maslach Burnout Inventory, respectively. The mediating effect of psychological resilience between occupational stress and job burnout was analyzed using the Process procedure, and the significance of the mediating effect was analyzed using the Bootstrap method. Results: A total of 383 people were investigated, among whom 370 were females (96.61%), and 13 were males (3.39%), with a mean age of (28.97±6.56) years. The scores of occupational stress, psychological resilience, and job burnout were (347.17±157.98), (87.18±13.17), and (56.07±17.09) points, respectively. The results of mediating effect analysis showed that occupational stress could directly positively affect job burnout with a direct effect value of 0.061 (95%CI: 0.004-0.119), and it could also indirectly positively affect job burnout through psychological resilience with a mediating effect value of 0.035 (95%CI: 0.002-0.122), and the mediating effect accounted for 57.38% of the total effect. Conclusions Occupational stress can directly or indirectly affect job burnout through psychological resilience. It is suggested to strengthen the mental health training of medical staff to improve psychological resilience and reduce job burnout.

OBJECTIVE To compare the anti-hepatitis mechanisms of Abrus pulchellus subsp. cantoniensis （Hance） Verdc. （AC） and Abrus pulchellus subsp. mollis（Hance） Verdc. （AM）. METHODS SD rats were randomly divided into blank group， AC- treated group， and AM-treated group， with each group consisting of 10 rats. The rats’ orbital venous blood was collected at 5， 15， 30 minutes， and 1， 1.5， 2， 4， 6， 8， 12 hours after gavage administration of 24 g/kg of the corresponding drug （calculated by crude drug） or water， respectively. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry technology was utilized to identify the prototype components present in the serum. The network pharmacology method was adopted to predict the anti-hepatitis active components， key targets， and signaling pathways of AC and AM. Additionally， molecular docking technology was utilized to verify the binding activity of the core active components with key targets. RESULTS A total of 35 prototype components migrating to the blood of AC and AM were identified in the serum of administered rats， among which 24 were common components. The active components in AC， such as acetylanguidine， physcion， soyasaponin A3 and soyasaponin Ⅰ， as well as those in AM， including vicenin 3， acetylanguidine，soyasaponin Ⅰ and schaftoside， all acted on key targets such as steroid receptor coactivator， phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit alpha， epidermal growth factor receptor （EGFR）， and protein kinase B1（Akt1）. These components modulated pathways in cancer， EGFR tyrosine kinase inhibitor resistance， and the phosphoinositide 3-kinase （PI3K） -Akt pathway， thereby exerting anti-hepatitis effects. Furthermore， the binding energies between these active components and their key targets were all less than －5 kJ/mol. CONCLUSIONS There are differences in the active components of AC and AM against hepatitis， but their mechanisms of action are similar. Both may exert their anti-hepatitis effects through pathways in cancer， EGFR tyrosine kinase inhibitor resistance， and the PI3K-Akt pathway.