ObjectiveTo investigate the mechanism of liver injury induced by tripterygium glycosides tablets （TG） and the molecular mechanism of compound glycyrrhizin tablets （CG） in alleviating the abnormalities of cholesterol metabolism caused by TG via cholesterol metabolism. MethodsAccording to the body weights， male Sprague-Dawley （SD） rats were randomly grouped as follows： control （pure water）， low-dose TG （TG-L， 189.0 mg·kg^-1·d^-1）， high-dose TG （TG-H， 472.5 mg·kg^-1·d^-1）， TG-L+CG （189.0 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， and TG-H+CG （472.5 mg·kg^-1·d^-1 TG + 20.25 mg·kg^-1·d^-1 CG）， with 6 rats in each group. Rats were administrated with corresponding drugs once daily for 3 weeks. At the end of the last administration， the mRNA and protein levels of liver X receptor-alpha （LXR-α）， low-density lipoprotein receptor （LDLR）， adenosine triphosphate-binding cassette transporter A1 （ABCA1）， adenosine triphosphate-binding cassette transporter G1 （ABCG1）， 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMGCR）， cholesterol 7α-hydroxylase （CYP7A1）， cholesterol 12α-hydroxylase （CYP8B1）， and sterol 27-hydroxylase （CYP27A1） in the liver tissue were determined by Real-time PCR and Western blotting， respectively. The level of 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMG-CoAR）， a regulatory enzyme of cholesterol synthesis， was measured by enzyme-linked immunosorbent assay （ELISA）. HepG2 cells were used to observe the effect of TG on the cell proliferation in vitro. Specifically， HepG2 cells were grouped as follows： Low-dose TG （TG-l， 15 mg·L^-1）， medium-dose TG （TG-m， 45 mg·L^-1）， high-dose TG （TG-h， 135 mg·L^-1）， fenofibrate （FB， 10 μmol·L^-1）， CG extract， TG-h+FB （135 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-m+FB （45 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-l+FB （15 mg·L^-1 TG + 10 μmol·L^-1 FB）， TG-h+CG （135 mg·L^-1 TG + 60 μmol·L^-1 CG）， TG-m+CG （45 mg·L^-1 TG + 60 μmol·L^-1 CG）， and TG-l+CG （15 mg·L^-1 TG + 60 μmol·L^-1 CG）. The mRNA and protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells were determined by Real-time PCR and Western blotting， respectively. ResultsThe rat experiment showed that compared with the control group， the TG-H group showed down-regulated mRNA levels of CYP7A1， CYP8B1， and CYP27A1 in the liver tissue （P<0.05， P<0.01）， which were up-regulated by the application of CG （P<0.05， P<0.01）， and the TG-H+CG group showed up-regulated mRNA level of LDLR （P<0.01）. Compared with the control group， the TG-L and TG-H groups showed down-regulated protein levels of LDLR， CYP7A1， and CYP8B1 in the liver tissue （P<0.05， P<0.01）. In addition， the protein levels of ABCG1 and LXR-α were down-regulated in the TG-H and TG-L groups， respectively （P<0.05）. Compared with TG alone， TG+CG up-regulated the protein levels of ABCG1 and LDLR （P<0.05， P<0.01）， and the protein levels of CYP7A1 and CYP8B1 in the TG-H+CG group were up-regulated （P<0.05， P<0.01）. The cell experiment showed that compared with the control group， the TG-h group presented up-regulated mRNA level of LXR-α （P<0.01）， and the TG-m and TG-h groups showcased down-regulated mRNA levels of LDLR and CYP7A1 （P<0.01） and up-regulated mRNA level of CYP27A1 （P<0.01） in HepG2 cells. The combination of CG with TG restored the above changes （P<0.01）. Western blotting results showed that compared with the control group， the TG-m and TG-h groups showed down-regulated protein levels of LXR-α， ABCG1， LDLR， CYP7A1， CYP8B1， and CYP27A1 in HepG2 cells （P<0.01）. Compared with the TG-h group， the TG-h+CG group showed up-regulated protein level of LDLR （P<0.05）. Compared with the TG-m group， the TG-m+CG group showcased up-regulated protein levels of LDLR， ABCG1， CYP7A1， and CYP27A1 （P<0.05， P<0.01）. ConclusionThe administration of TG at 189.0， 472.5 mg·kg^-1 for 3 weeks could modulate the signaling pathways associated with cholesterol efflux， endocytosis， and cholesterol biotransformation in hepatocytes， leading to the accumulation of cholesterol and subsequent liver injury in rats. CG could ameliorate the liver injury induced by lipid metabolism disorders caused by TG by up-regulating the expression of LXR-α， LDLR， ABCG1， CYP7A1， CYP8B1， and CYP27A1 to promote cholesterol biotransformation.

Stroke-associated sarcopenia is a serious post-stroke complication that can have a significant impact on patient’s functional recovery. However， currently available assessment tools for sarcopenia require specialized equipment and personnel， which are difficult to access in resource-limited settings. This article presents the role of biomarkers as an objective method in the pathogenesis， prevention， diagnosis， and prognostic assessment of stroke-associated sarcopenia， with the focus on neuromuscular， inflammatory， metabolic， and nutritional indicators.
Stroke ; Sarcopenia ; Biomarkers

ObjectiveTo investigate the effect and molecular mechanism of exosomes derived from bone marrow mesenchymal stem cells（BMSC-exos） modified with Bushen Yisui capsule（BSYS）-containing serum on promoting the differentiation and maturation of OLN-93 oligodendrocytes by regulating miR-15b/Wnt signaling pathway. MethodsOLN-93 cells were divided into 5 groups， including the normal（NC） group， BMSC-exos group， BSYS-BMSC-exos group， BSYS-BMSC+LV-miR-15b-5p inhibitor-exos group， and BSYS-BMSC+LV-miR-15b-5p NC-exos group. DiR staining was used to observe the uptake of Exos by OLN-93 cells. The effective dosage of BSYS-BMSC-exos on OLN-93 cells was assessed by cell proliferation and activity assay（CCK-8）. Stable BMSCs lentiviral transfection strains were established to inhibit miR-15b-5p expression in both BMSCs and their exos， and transfection efficiency was verified by real-time fluorescent quantitative polymerase chain reaction（Real-time PCR） detection of miR-15b-5p. The expressions of 2′，3′-cyclic nucleotide 3′-phosphodiesterase（CNPase） and myelin proteolipid protein（PLP） in OLN-93 cells were detected by immunocytochemistry（ICC） and Western blot. The mRNA expressions of miR-15b-5p and Wnt3a in OLN-93 cells were detected by Real-time PCR， and the protein expression of Wnt3a was measured by Western blot. The expression levels of key molecules in the Wnt/β-catenin signaling pathway of OLN-93 cells， including glycogen synthase kinase（GSK）-3β， β-catenin， and T-cell specific transcription factor 4/transcription factor 7-like 2（TCF4/TCF7L2）， were measured by Real-time PCR and Western blot. ResultsDiR-labeled Exos were efficiently taken up by OLN-93 cells. The CCK-8 assay results indicated that 20 mg·L^-1 of BSYS-BMSC-exos exhibited the most significant effect in enhancing OLN-93 cell viability（P<0.01） and this dosage was selected for subsequent experiments. Following lentiviral transfection of BMSCs， Real-time PCR results revealed that miR-15b-5p was significantly suppressed in BMSCs（P<0.01）， and miR-15b-5p was also notably inhibited in BSYS-BMSC-exos（P<0.01）. ICC analysis further revealed an increase in the number of differentiated， mature CNPase and PLP-positive cells following BSYS-BMSC-exos treatment（P<0.01）. Western blot results demonstrated that the protein expression of CNPase and PLP was significantly enhanced with BSYS-BMSC-exos treatment（P<0.01）. Additionally， BSYS-BMSC-exos also increased the expression levels of miR-15b-5p and p-β-catenin proteins in OLN-93 cells， while decreased the mRNA and protein expressions of Wnt3a， as well as the mRNA expressions of β-catenin and TCF4/TCF7L2， and the protein expression level of p-GSK-3β（Ser9） was significantly reduced（P<0.05， P<0.01）. After the transfection of miR-15b-5p inhibitor into BSYS-BMSC-exos， the above effects were significantly diminished（P<0.05， P<0.01）. ConclusionBSYS-BMSC-exos facilitate the differentiation and maturation of OLN-93 cells， and its mechanism is related to the upregulation of miR-15b-5p in OLN-93 cells， which inhibits the expression of Wnt3a and thereby suppresses the Wnt signaling pathway.

Background::Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors.Methods::The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020.Results::The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy.Conclusions::We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.

Objective To observe the value of intravascular ultrasound(IVUS)for assisting endovascular therapy for renal artery stenosis(RAS).Methods Thirty patients with RAS who underwent endovascular therapy were retrospectively analyzed.Parameters of renal artery and plaques in RAS segment measured with CT angiography(CTA)and IVUS before treatment were compared.Bland-Altman diagram was performed to evaluate the consistency of lumen cross-sectional stenosis rate and plaque eccentricity index between CTA and IVUS.The stent parameters measured with IVUS were recorded immediately after implantation of balloon-expandable covered stents.Results Before treatment,the minimum lumen diameter,lumen cross-sectional stenosis rate and stenotic segment length of IVUS were all larger,while maximum lumen diameter and lumen eccentricity index of IVUS were both smaller than those of CTA(all P＜0.05).No significant difference of plaque eccentricity index,plaque type nor stenosis distal remodeling was found between CTA and IVUS(all P＞0.05).The average difference between IVUS and CTA for evaluating lumen cross-sectional stenosis rate and plaque eccentricity index was-0.020(-0.096,0.050)and-0.020(-0.130,0.091),respectively.The consistency of IVUS and CTA for evaluating plaque eccentricity index was better than that of lumen cross-sectional stenosis rate.The stent symmetry,stent eccentricity index,stent expansion coefficient and stenosis coverage rate immediately after implantation measured with IVUS was(82.69±14.61)%,(1.54±9.16)%,(99.81±10.70)%and 100%,respectively.Among 30 cases,2 cases(2/30,6.67%)underwent postdilation since poor stent apposition.Conclusion IVUS could assist evaluating lumen and plaque parameters of stenotic renal arteries,guiding stent release and real-timely monitoring the effect of endovascular therapy.

Objective:To synthesize the real experiences of medical staff's organizational silence behavior.Methods:A systematic search was conducted in databases including PubMed, Web of Science, Embase, Cochrane Library, CINAHL, EBSCO, ProQuest, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biology Medicine disc, collecting qualitative studies on medical staff's experiences related to organizational silence behavior. The search period covered the establishment of the databases until June 2024. The quality of the included studies was assessed using the Joanna Briggs Institute's qualitative research quality evaluation standards, and results were integrated using an aggregative synthesis approach.Results:A total of 10 studies were included, with 65 findings summarized into 11 new categories, which were further synthesized into four overarching conclusions: organizational silence is complex, with respect and concern coexisting, many factors contribute to organizational silence, medical staff experience negative emotions as a result of organizational silence, there is a desire for recognition and support.Conclusions:The experience of organizational silence behavior among medical staff is complex. Managers should focus on this issue, encourage individuals to voice their concerns, provide diverse support mechanisms, and enhance positive experiences to reduce the prevalence of organizational silence.

Objective:To investigate the efficacy of color Doppler ultrasound-guided percutaneous nephrostomy in the treatment of anastomotic leakage after laparoscopic pyeloplasty.Methods:A retrospective analysis was performed for the data of 15 children with peritoneal irritation after LP who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2018 to January 2023, of which 10 cases were anastomotic leaks and 5 cases were with renal pelvic blood clots. There were 12 males and 3 females. Age (4.2±2.7) years. The lesions were located on the left side of 11 cases and on the right side of 4 cases. All 15 cases had varying degrees of nausea, vomiting, abdominal pain and other symptoms. Physical examination: the children all showed painful faces and tense abdominal muscles. 15 patients had a preoperative pain score of 9.5 (8, 10). Ultrasound examination showed that the anterior and posterior diameters of renal pelvis separation were (34.93±4.86) mm, the anterior and posterior diameter/renal parenchymal thickness of renal pelvis separation was 15.66±1.02, renal dynamic nuclear imaging shows the renal function of the affected side was (29.69±1.71)%. Thirteen cases had the above symptoms before the abdominal drainage tube was removed, and the time of symptom onset was (3.3±1.1) days after surgery, of which 8 cases had a large increase in abdominal drainage, and color Doppler ultrasonography showed a large amount of fluid in the intra-abdominal intestinal space (about 500 ml). In 5 cases, the intraperitoneal drainage volume did not increase, and color Doppler ultrasonography showed strong echo in the renal pelvis, and blood clots were considered. All 13 patients were placed in the prone position under local anesthesia and underwent color Doppler ultrasound-guided percutaneous nephrostomy. The remaining 2 cases had abdominal drainage tube removed on the 3rd day after surgery, and peritoneal irritation signs appeared on the 4th and 6th days after surgery, respectively. Color Doppler ultrasonography showed that there was a large amount of fluid in the intra-abdominal intestinal space, and color Doppler ultrasound-guided peritoneal puncture and drainage + prone percutaneous nephrostomy was performed in the supine position under local anesthesia, and the biochemical analysis of the peritoneal puncture drainage fluid was confirmed to be anastomotic urine leakage. The drainage volume and urine output of 15 cases of peritoneal puncture drainage and pyelostomy were recorded, and the relief of nausea and vomiting symptoms and the score of postoperative pain after percutaneous nephrostomy were recorded. The changes of hydronephrosis and renal function before and after percutaneous nephrostomy were compared.Results:In this study, 15 patients underwent percutaneous nephrostomy with a duration of (16.8±1.9) min. The symptoms of nausea and vomiting disappeared after operation, and the pain scores were 3.2(2, 4) and 0.4(0, 2) at 2 h and 12 h after operation, respectively, which were statistically significant compared with those before operation ( P<0.01). In 13 children with simple percutaneous nephrostomy, the abdominal drainage tube was removed on (3.6±0.8) days and (8.6±1.0) days after percutaneous nephrostomy. In 2 children with peritoneal puncture and drainage plus percutaneous nephrostomy, the abdominal drainage tube was removed 3 days after the fistula operation, and the pyelostomy tube was removed 8 days after the fistula operation. The anterior and posterior diameters of renal pelvis separation were (10.87±4.05), (10.13±3.50) and (9.13±3.11) mm by color Doppler ultrasound at 3, 6 and 12 months after LP operation, respectively, and there were statistically significant differences compared with preoperative comparisons ( P<0.01).The diameter before and after renal pelvis separation was (7.60±2.86) mm, the diameter before and after renal pelvic separation/renal parenchymal thickness was 1.97±0.22, and the renal function was (39.23±2.66)% at 24 months after operation, which was statistically significant compared with that before operation ( P<0.01). Conclusions:Color Doppler ultrasound-guided percutaneous nephrostomy can effectively alleviate symptoms in the early stage, which could help to the healing of ureteral anastomosis, and has less trauma and short operation course.

Objective:To investigate the feasibility and safety of a treatment system for stentless discharge after flexible ureteroscopic lithotripsy assisted by flexible negative pressure sheath.Methods:The clinical data of 72 patients with upper urinary calculi admitted to the Second Hospital of Tianjin Medical University from November 2022 to February 2023 were retrospectively analyzed. All patients achieved stentless discharge after flexible ureteroscopic lithotripsy assisted by flexible negative pressure sheath. There were 50 males and 22 females. The average age was (54.7±12.1) years. Preoperative urine culture was positive in 14 cases, negative in 3 cases (4.2%)with nitrite positive, and 11 cases were negative for urine culture and nitrites but positive of white blood cells (+ + + ). There were 29 cases of renal calculi, 33 cases of upper ureteral calculi, and 10 cases of upper ureteral calculi combined with renal calculi.The mean stone diameter was 17.0(14.0, 24.0)mm. CT value was (1 049.3±258.6)HU. Twenty-four patients carried ureteral stents before operation. A total of 42 cases used ureteral sheaths with diameters of F11/13, and 30 cases used sheaths with diameters of F12/14.During the operation, an infusion pump was used to provide sufficient irrigation pressure. The negative pressure suction was attached to the distal end of the sheath. The flexible head of the sheath was guided to the target renal calyx, to completely aspirate stone fragments. Stone baskets was used in 11 cases during the procedure. The level of ureteral injury was assessed according to the Traxer grading system at the end of the operation. A ureteral stent with extraction string was retained.On the first day postoperatively, CT scanning was performed to evaluate the residual stone fragments. Patients were discharged on postoperative day 2-3 after the removal of the ureteral stent and catheter. Follow-up was conducted for 30 days postoperatively, during which the Ureteral Stent Symptom Questionnaire (USSQ) was used to assess voiding symptoms and pain. Painkiller usage and emergency revisit situations were recorded. CT scans were performed to evaluate the stone-free rate on postoperative day 30.Results:The average operation time was 30.0 (20.0, 44.5) minutes. A total of 70 cases had no ureteral injuries, and 2 cases had Grade 1 ureteral injuries (minor mucosal damage). Three cases developed fever within 72 hours postoperatively, with no cases of septic shock or fever after stent removal. Eight patients reported waist and abdominal discomfort after discharge and took oral pain medication. Among them, one patient returned to the emergency department for pain treatment. Five patients reported moderate or severe genitourinary symptoms (including voiding frequency, nocturia, urgency/incontinence, dysuria, hematuria, and incomplete emptying) based on subjective evaluation. All patients could work and recovered a normal daily life after discharge and there was no readmission or additional surgical procedures. There were 61 patients achieved immediate stone-free status on the first day after surgery, and 66 patients achieved stone-free status during follow-up at 30 days postoperatively.Conclusions:Stentless discharge after flexible ureteroscopic lithotripsy assisted by flexible negative pressure sheath is safe and feasible.

Objective:To evaluate the effect of patient-controlled intravenous analgesia (PCIA) with esketamine mixed with hydromorphone on the postoperative sleep quality in pediatric patients.Methods:This was a prospective randomised controlled study. One hundred pediatric patients of both sexes, aged 4-12 yr, with a body mass index of 13-26 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective abdominal surgery with general anesthesia, who agreed to use postoperative patient-controlled intravenous analgesia in our hospital from January to November 2023, were divided into esktamine mixed with hydromorphone group (EH group) and hydromorphone group (H group), with 50 patients in each group. PCIA solution contained esketamine 1 mg/kg and hydromorphon 0.1 mg/kg in 100 ml of 0.9% sodium chloride in EH group and hydromorphone 0.2 mg/kg in 100 ml of 0.9% sodium chloride in H group. The Pittsburgh Sleep Quality Index was used to evaluate the preoperative sleep quality by asking pediatric patients themselves or their guardians. On the morning of 1-3 days after surgery, the numeric rating scale (NRS) was used to evaluate the sleep quality of the first 3 nights after surgery. At 24 and 48 h after surgery, the FLACC pain scale was used to evaluate the intensity of pain. The consumption of hydromorphone within 48 h after surgery and the incidence of postoperative adverse reactions such as nausea, vomiting, itching and delirium were recorded. Results:Compared with group H, the NRS score was significantly increased on the 1st postoperative night, the ratio of poor sleep quality was decreased ( P<0.05), and no significant change was found in the NRS score on the 2nd or 3rd postoperative night and ratio of poor sleep quality ( P>0.05), and the FLACC pain scale score at 24 and 48 h after surgery and consumption of hydromorphone within 48 h after surgery were decreased in group EH ( P<0.05). There was no significant difference in the incidence of postoperative adverse reactions between the two groups ( P>0.05). Conclusions:PCIA with esketamine mixed with hydromorphone can improve the postoperative sleep quality in pediatric patients.

Objective:To explore the efficacy and safety of Neuroform Atlas stent-assisted coil embolization in ruptured anterior communicating wide-necked aneurysms.Methods:Thirty-two patients with ruptured anterior communicating wide-necked aneurysms accepted Neuroform Atlas stent assisted coil embolization in Department of Neurosurgery, People's Hospital Affiliated to Shandong First Medical University from January 2022 to June 2023 were chosen. DSA was performed immediately after surgery, and aneurysm embolization was assessed using Raymond grading. Prognoses were assessed by modified Rankin Scale (mRS, mRS scores≤2 as good prognosis and mRS scores>2 as poor prognosis) at last follow-up. DSA was performed again 6 months after surgery to assess the aneurysm healingResults:Neuroform Atlas stents were successfully implanted in all 32 patients; Postoperative DSA showed that aneurysm embolization reached Raymond grading I in all 32 patients(100%). No such complications as in-stent thrombosis, cerebral vasospasm, or poor opening of the stent were noted excepted for one with intraoperative aneurysm rupture hemorrhage. At the last follow-up, 31 patients had good prognosis and 1 had poor prognosis; in 22 patients underwent DSA re-examination, Raymond grading I was noted in 20 patients (90.91%) and grading II in 2 (9.09%).Conclusion:Neuroform Atlas stent-assisted coil embolization for ruptured anterior communicating wide-necked aneurysms seems safe and effective.