Objective: To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice. Methods: Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue. Results: Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group. Conclusion Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.

ObjectiveTo study the mechanism of Shexiang Tongxin Dripping pills-containing serum （STDP） in ameliorating angiotensinⅡ （AngⅡ）-induced cell phenotype transformation， proliferation， migration， and dysfunction of vascular smooth muscle cells. MethodsAn AngⅡ-induced proliferation and migration model of vascular smooth muscle cells was established. The cells were treated with STDP at 5%， 10%， and 20% for 24 h. The immunofluorescence assay was employed to detect the expression of α smooth muscle actin （α-SMA） and matrix metalloproteinase-2 （MMP-2）. The cell-counting kit-8 （CCK-8） assay and 5-ethynyl-2'-deoxyuridine （EdU） staining were employed to detect the proliferation of vascular smooth muscle cells， and the scratch assay was employed to detect the migration of the cells. Western blot was employed to determine the expression levels of pathway proteins such as angiotensin-converting enzyme 2 （ACE2）， angiotensin Ⅱ type 2 （AT2）， angiotensin Ⅱ type 1 （AT1）， as well as proliferation and migration proteins such as typeⅠ collagen （ColⅠ） and osteopontin （OPN）. ResultsCompared with the model group， STDP increased the expression of α-SMA， reduced the expression of MMP-2， and inhibited the proliferation and migration of vascular smooth muscle cells （P<0.05）. Furthermore， STDP up-regulated the expression levels of ACE2， AT2， and MAS1， while down-regulating the expression level of AT1， PCNA， ColⅠ， MMP-9， Rock1， Rock2， and SRF （P<0.05）. Compared with the STDP group， the ACE2 inhibitor reversed the regulatory effects of STDP. ConclusionSTDP inhibits the phenotype transformation， proliferation， and migration of vascular smooth muscle cells and regulates the expression of cell proliferation and migration-related proteins to ameliorate the dysfunction of vascular smooth muscle cells. It exerts the effects by up-regulating the expression of proteins in the ACE2-AT2/MAS pathway and down-regulating the expression of proteins in the AT1-Rock signaling pathway.

Objective To explore the pathogenesis and prognostic factors of liposarcoma in the head and neck region, and simultaneously analyze the efficacy of different treatment regimens. Methods A retrospective analysis was performed on all patients with primary untreated head and neck liposarcoma who were diagnosed and underwent surgical treatment at our hospital from January 2008 to January 2024. All patients were monitored during follow-up, and their prognoses were analyzed using SPSS software. Results A total of 30 patients were included in the study. Liposarcoma accounted for up to 60% of the cases in the orbit, while the remaining liposarcomas were primarily located in various interspaces of the neck. Dedifferentiated liposarcoma was the most common type, comprising 33%, while myxoid pleomorphic liposarcoma was the rarest at 4%. The tumor pathological type (P<0.001) and Ki67 (P=0.014) significantly affected the tumor control rate. However, an analysis of disease-specific survival rates revealed no significant differences across various factors (all P>0.05). Conclusion The prognosis of head and neck liposarcoma is better compared to that of liposarcomas in other parts of the body. However, myxoid pleomorphic liposarcoma, pleomorphic fat sarcoma, and high Ki67 levels are indicators of poor prognosis. Additionally, postoperative adjuvant radiotherapy does not significantly enhance disease-specific survival rates.

ObjectiveTo study the mechanism by which Shexiang Tongxin dropping pills （STDP） ameliorate the dysfunction of coronary microvascular endothelial cells in the rat model of heart failure. MethodsThe heart failure model was established by ligation of the left anterior descending coronary artery in rats， which were then allocated into sham， model， STDP， and telmisartan （TLM） groups and treated for 21 days. The heart function was detected by echocardiography， and the levels of myocardial injury markers， nitric oxide （NO）， endothelin-1 （ET1）， and angiotensinⅡ （AngⅡ） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein levels of endothelial nitric oxide synthase （eNOS） and inducible nitric oxide synthase （iNOS） were determined by Western blot. The model of cardiac microvascular endothelial cell injury was established by AngⅡ induction and then treated with the STDP-containing serum （5%， 10%， and 20%） for 24 h. The levels of NO and ET1 were measured by ELISA. Western blot was employed to determine the protein levels of eNOS， iNOS， angiotensin-converting enzyme 2 （ACE2）， and angiotensinⅡ receptor 2 （AT2）. MLN-4760， an ACE2 inhibitor， was used to explore the mechanism underpinning the regulatory effect of STDP on the ACE2-AT2/MAS pathway. ResultsCompared with the sham group， the model group showed decreases in left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.05）， a decline in serum NO level， elevations in serum AngⅡ and ET1 levels， a reduction in p-eNOS/eNOS ratio， and up-regulation in iNOS expression （P<0.05）. Compared with the model group， STDP increased LVEF， LVFS， and cardiac output （P<0.05）， raised the level of NO and lowered the levels of AngⅡ and ET1 in the serum （P<0.05）， increased the p-eNOS/eNOS value， and inhibited iNOS expression （P<0.05）. Compared with the AngⅡ group， STDP increased the NO content and decreased the ET1 content in endothelial cells （P<0.05）， increased the p-eNOS/eNOS ratio， and inhibited the iNOS expression （P<0.05）. The ACE2 inhibitor MLN-4760 reversed the regulatory effects of STDP on p-eNOS， eNOS， and iNOS. ConclusionSTDP improves the cardiac function in the rat model of heart failure， enhances the synthesis and release of NO in cardiac microvascular endothelial cells， reduces AngⅡ and ET1 levels， and regulates the expression of p-eNOS and eNOS， thereby ameliorating the dysfunction of microvascular endothelial cells in heart failure. This mechanism is related to the upregulation of the expression of proteins in the ACE2-AT2/MAS pathway.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

Objective To examine the significance of susceptible gene detection for hereditary cancer syndrome (HCS) among general population. Methods A total of 2 928 individuals undergoing routine health examinations in Healthcare Center of Zhongshan Hospital, Fudan University, from September 2021 to April 2024 were enrolled retrospectively. Next generation sequencing was employed to identify susceptible genes for HCS. American College of Medical Genetics and Genomics (ACMG) guideline was used to analyze the pathogenicity of variants. Clinical data, imagings, follow-up data were also collected. Results The overall mutation rate of HCS panel was 3.59% (105/2 928), with 0.61% (18/2 928) for MutY DNA glycosylase (MUTYH), 0.27% (8/2 928) for breast cancer susceptibility gene 1/2 (BRCA1/2) and 0.23% (7/2 928) for mismatch repair (MMR) genes. Conclusions Healthy individuals carrying tumor susceptible genes usually lack the relevant clinical phenotypes. Whether comprehensive testing needs to be carried out among healthy people remains to be further explored.

Aim To investigate the involvement of mesencephalic astrocyte-derived neurotrophic factor(MANF)in rifampicin(RFP)-induced cholestatic liv-er injury.Methods We investigated the impact of MANF gene deletion on rifampicin-induced BAT ex-pression in mice by the MANF gene knockout mouse model.We investigated the influence of MANF knock-down on nuclear factor erythroid 2-related factor 2(Nrf2)in HepG2 cells by the MANF knockdown cell model.Results Compared with the wild-type(WT)mice,the mRNA and protein expression levels of bile salt export pump(BSEP)and multidrug-resistant asso-ciated protein4(MRP4)significantly increased in WT mice treated with RFP.However,compared to the WT mice treated with RFP,the mRNA and protein expres-sion levels of BSEP,Multidrug resistance protein 1(MDR1),multidrug resistance associated proteins 2/3/4(MRP2/3/4),and organic solute transport pro-teins α(OST α)were significantly reduced.In cell experiments we found that MANF knockdown weakened the expression of Nrf2 and its nuclear translocation by RFP.Conclusion MANF may regulate adaptive BAT expression by modulating Nrf2 expression,thereby pla-ying a protective role in RFP-induced liver injury.

Objective To establish the finite element model of spinal canal reconstruction and internal fixation,analysis influence of spinal canal reconstruction and internal fixation on spinal stability,and verify the effectiveness and reliability of spinal canal reconstruction and internal fixation in spinal canal surgery.Methods A 30-year-old male healthy volunteer with a height of 172 cm and weight of 75 kg was selected and his lumbar CT data were collected to establish a finite element model of normal lumbar Lo3-L,and the results were compared with in vitro solid results and published finite element analysis results to verify the validity of the model.They were divided into normal group,laminectomy group and spinal canal reconstruction group according to different treatment methods.Under the same boundary fixation and physiological load conditions,six kinds of ac-tivities were performed,including forward bending,backward extension,left bending,right bending,left rotation and right rota-tion,and the changes of range of motion(ROM)of L3-L4,L4-L5 segments and overall maximum ROM of L3-L5 were analyzed under the six conditions.Results The ROM displacement range of each segment of the constructed L3-L5 finite element model was consistent with the in vitro solid results and previous literature data,which confirms the validity of the model.In L3-L4,ROM of spinal canal reconstruction group was slightly increased than that of normal group during posterior extension(＞5％dif-ference),and ROM of other conditions was similar to that of normal group(＜5％difference).ROM in laminectomy group was significantly increase than that in normal group and spinal canal reconstruction group under the condition of flexion,extension,left and right rotation.In L4-L5,ROM in spinal canal reconstruction group was similar to that in normal group(＜5％differ-ence),while ROM in laminectomy group was significantly higher than that in normal group and spinal canal reconstruction group(＞5％difference).In the overall maximum ROM of L3-L5,spinal canal reconstruction group was only slightly higher than normal group under the condition of posterior extension(＞5％difference),while laminectomy was significantly higher than normal group and spinal canal reconstruction group under the condition of anterior flexion,posterior extension,left and right rotation(＞5％difference).The changes of each segment ROM and overall ROM of L3-L5 showed laminectomy group＞spinal canal reconstruction group＞normal group.Conclusion Laminectomy could seriously affect biomechanical stability of the spine,but application of spinal canal reconstruction and internal fixation could effectively reduce ROM displacement of the responsi-ble segment of spine and maintain its biomechanical stability.

Objective To explore clinical efficacy of autologous bone grafts and bone substitute for the treatment of tibial plateau fractures by Meta analysis.Methods Controlled clinical studies on autogenous bone transplantation and bone substitutes in treating tibial plateau fractures published on PubMed,Web of Science,CNKI,Wanfang and other databases from January 2005 to August 2022 were searched by computer.Literature screening and data extraction were performed according to random-ized controlled trial(RCT),and the quality of RCT were evaluated by using intervention meta-analysis criteria in Cochrane man-ual.Meta-analysis of joint depression,secondary collapse rate of articular surface,blood loss,operative time and infection rate between two methods were performed by Rev Man 5.3 software.Results Seven RCT studies(424 patients)were included,296 patients in bone replacement group and 128 patients in autograft group.Operative time[MD=-16.79,95％CI(-25.72,-7.85),P=0.000 2]and blood loss[MD=-70.49,95％CI(-79.34,-61.65),P＜0.000 01]between two groups had statistically differ-ences,while joint depression[MD=-0.17,95％CI(-0.91,0.58),P=0.66],secondary collapse rate of joint surface[RR=-0.74,95％CI(0.35,1.57),P=0.43],infection rate[RR=1.21,95％CI(0.31,4.70),P=0.78]between two groups had no differences.Conclusion The effects of bone substitute and autograft for the treatment of tibial plateau fracture have similar effects in terms of joint depression,secondary articular surface collapse rate and infection rate.However,compared with autologous bone trans-plantation,bone replacement could reduce blood loss and shorten operation time.

Objective To explore planning effect of AI-HIP assisted surgical planning system in primary unilateral total hip arthroplasty(THA)and its influence on clinical outcomes.Methods A retrospective analysis was conducted on clinical data of 36 patients who underwent their first unilateral THA from March 2022 to November 2022 and continuously used AI-HIP system(AI-HIP group),including 16 males and 20 females,aged from 43 to 81 years old with an average of(62.2±10.9)years old.According to the matching principle,36 patients who were planned by the traditional template method at the same period were selected as the control group,including 16 males and 20 females,aged from 40 to 80 years old with an average of(60.9±12.1)years old.The accuracy between two groups of prostheses were compared,as well as the combined eccentricity difference between preoperative planning and postoperative practice,lower limb length difference,osteotomy height from the upper edge of the lesser trochanter and top shoulder distance to evaluate planning effect.Harris score and visual analogue scale(VAS)were used to evaluate clinical efficacy.Results Both groups were followed up for 12 to 18 months with an average of(14.5±2.1)months.The complete accuracy and approximate accuracy of acetabular cup and femoral stalk prosthesis in AI-HIP group were 72.2％,100％,58.3％,88.9％,respectively,which were better than 44.4％,83.3％,33.3％,66.7％in control group(P＜0.05).There was no statistical significance in planning of femoral head prosthesis size(P＞0.05).The actual combined eccentricity difference and combined eccentricity difference(practical-planning)in Al-HIP group were 1.0(0.2,2.4)mm and 1.1(-2.1,3.2)mm,respectively;which were better than 3.0(1.4,4.9)mm and 3.5(-1.6,6.5)mm in control group(P＜0.05).There was no significant difference between two groups in actual osteotomy height of the upper margin of the lesser trochanter(P＞0.05).In AI-HIP group,the actual difference of lower extremity length after surgery,the difference of lower extremity length(practical-planning),osteotomy height from the upper margin of lesser trochanter(practical-planning),actual topshoulder distance after surgery,and topshoulder distance(practical-planning)were 1.5(0.2,2.8),1.1(-0.3,2.2),2.1(-2.3,4.1),(15.3±4.1),2.2(-4.8,0.3)mm,respectively;which were better than control group of 2.6(1.3,4.1),2.5(0.3,3.8),5.8(-2.4,7.7),(13.0±4.3),-5.7(-9.4,-2.2)mm(P＜0.05).At final follow-up,there were no significant differences in Harris scores of pain,function,deformity,total scores and VAS between two groups(P＞0.05).The range of motion score was 4.8±0.6 in AI-HIP group,which was higher than that in control group(4.4±0.8)(P＜0.05).Conclusion Compared with traditional template planning,AI-HIP assisted surgical planning system has good accuracy in predicting the prosthetic size of the acetabular cup and femoral stalk,restor-ing joint eccentricity,planning lower limb length,osteotomy height and top shoulder distance on the first unilateral THA,and the clinical follow-up effect is satisfactory.