BACKGROUND:Satisfactory clinical results have been achieved in the treatment of Sanders Ⅲ calcaneal fractures by percutaneous compression fixation with three-dimensional frame screws.However,whether the stability of minimally invasive plate internal fixation can be achieved in terms of biomechanics,and the advantages and disadvantages after comparison are still unknown. OBJECTIVE:To investigate the fixation effect of different internal fixation devices on Sanders Ⅲ calcaneal fractures by finite element analysis. METHODS:A finite element model of Sanders Ⅲ calcaneal fracture was made based on CT data of a 26-year-old healthy male volunteer.The calcaneal fracture models were fixed by minimally invasive three-dimensional frame screws and minimally invasive Y-plate.The longitudinal loads of 350 and 700 N were applied respectively.The displacement and stress distribution of the two models were analyzed,and the stability of each model was compared. RESULTS AND CONCLUSION:(1)The peak stress of bone block and implant in the minimally invasive three-dimensional frame screw model was significantly lower than that in the minimally invasive minimally invasive plate model.The average stress of bone block and implant in the three-dimensional frame screw model was also significantly lower than that in the minimally invasive plate model.(2)The maximum displacement of the two models was located at the medial side of the articular surface of the posterior talus,and the maximum displacement of the three-dimensional frame screw model was smaller than that of the minimally invasive plate model.(3)The longitudinal displacement between the anterior fragment and the medial fragment of the minimally invasive plate model was smaller,and the transverse and vertical displacement between the medial fragment and the middle fragment of the three-dimensional group screw model was smaller.(4)It is concluded that both of the two internal fixation models can provide satisfactory fixation effect.The three-dimensional frame screw model can provide better transverse and vertical stability with more uniform stress distribution and smaller comprehensive displacement of bone fragments,while the minimally invasive plate has more advantages in maintaining longitudinal stability.

Aim To explore the effect of circ_0038467 on nerve cell damage induced by hypoxia-glucose dep-rivation(OGD)and its possible mechanism.Methods Rat cortical nerve cells were isolated and cultured,and then induced by OGD to establish a cell injury model.si-NC,si-circ_0038467,miR-NC,and miR-940 mimics were transfected into rat cortical nerve cells and treated with OGD for 6 h.si-circ_0038467 and an-ti-miR-NC or anti-miR-940 were co-transfected into rat cortical neurons,followed by OGD treatment for 6 h.qRT-PCR was used to detect the expression levels of circ_0038467 and miR-940.CCK-8 method and flow cytometry were used to examine cell proliferation and apoptosis.LDH method was used to detect cell dam-age.The dual luciferase reporter experiment was used to detect the targeting relationship between circ_0038467 and miR-940.Western blot was employed to detect cleaved caspase-3 and cleaved caspase-9 protein levels.Results Circ_0038467 expression increased and miR-940 expression decreased in OGD-induced nerve cells(P＜0.01).After transfection with si-circ_0038467 or miR-940 mimics,cell survival rate in-creased(P＜0.01),while LDH release rate,apopto-sis rate,and the protein levels of cleaved caspase-3 and cleaved caspase-9 decreased(P＜0.01).Circ_0038467 could target miR-940.Compared with the OGD+si-circ_0038467+anti-miR-NC group,cell survival rate in OGD+si-circ_0038467+anti-miR-940 group was down-regulated(P＜0.01),while LDH re-lease rate,apoptosis rate and cleaved caspase-3,cleaved caspase-9 levels were up-regulated(P＜0.01).Conclusion Interference of circ_003 8467 and could protect nerve cells from OGD-induced oxidative stress and apoptosis by up-regulating miR-940.

Objective To screen and analyze the influencing factors of severity in the patients with type 2 diabetes mellitus (T2DM) complicating cerebral small vessel disease (CSVD).Methods A total of 519 pa-tients with T2DM complicating CSVD admitted and treated in Nanjing Municipal Hospital of Traditional Chi-nese Medicine from June 2018 to May 2023 were selected and divided into the mild group (n=214) and the se-vere group (n=305) according to the CSVD imageological score.The relevant demographic,laboratory and imageological indicators were collected.The influencing factors of T2DM complicating CSVD were screened out by the LASSO and Logistic regression analysis and the predictive model was established.The receiver op-erating characteristic (ROC) curve,goodness of fit evaluation and restricted cubic spline (RCS) fitting curve were drawn to analyze the dose-response relationship between Cys C,albumin/globulin (A/G) ratio with the disease severity.Results The male proportion and age in the severe group were greater than those in the mild group,neutrophil,systemic immune-inflammation index (SII),creatinine (Crea),uric acid (UA),Urea (Ure-a),D-dimer (D-D),lactate dehydrogenase (LDH),adenosine deaminase (ADA),globulin (GLB) and Cys C were higher than those in the mild group,lymphocyte,ALT,High density Lipoprotein-cholesterol (HDL-C),serum cholinesterase (CHE),prealbumin (PAB),and A/G were lower than those in the mild group,and the differences were statistically significant (P<0.05).LASSO and logistic regression analysis showed that the gender,age,A/G and Cys C were the independent influencing factors in the patients with T2DM complicating CSVD.The area under the curve (AUC) of this model was 0.658 (95%CI:0.610-0.706) with goodness of fit (P=0.520).The RCS fitting curves showed that serum Cys C≥0.618 mg/L had a linear relationship with CSVD imageological score (P=0.035),and A/G≥1.268 had a nonlinear relationship with CSVD imageologi-cal score (P=0.007).Conclusion The advanced age,male,increased Cys C level and decreased A/G in the pa-tients with T2DM complicating CSVD are the independent risk factors for the severity of whole brain damage.

Objective To screen the characteristic factors of renal impairment occurrence in the patients with hyperuricemia,and to analyze its diagnostic value and establish a diagnostic model.Methods A total of 2405 inpatients with diagnosed hyperuricemia in the Nanjing Municipal Hospital of Traditional Chinese Medi-cine,Nanjing University of Traditional Chinese Medicine from December 2018 to December 2022 were selected and divided into the kidney lesion group (n=1343) and the non-kidney lesion group (n=1062) according to eGFR.The characteristic factors of hyperuricemia caused renal impairment were screened and analyzed by Lasso and logistic regression and the diagnostic model was constructed.The diagnostic value of characteristic factors and diagnostic model were evaluated by the receiver operating characteristic (ROC) curve,and the change rule between the characteristic factors and the results was found by the restricted cubic splines (RCS) fitting.Results The age,uric acid (UA),cystatin-C (Cys-C) and retinol-binding protein (RBP) were the characteristic factors of hyperuricemia caused renal impairment.The combined diagnostic model:logit (P)=-8.70+0.602×age (10 years old)+0.033×UA (10 μmol/L)+0.277×Cys-C (0.1 mg/L)+0.189×RBP (10 mg/L),the area under the ROC curve (AUC) of the combined diagnosis model was 0.893 (95％CI:0.880-0.905).For every 10 μmol/L increase in blood UA,the risk of renal impairment occurrence in hyperurice-mia was increased by 3％;for every 10 years increase in age,the risk of renal impairment occurrence in hyperu-ricemia was increased by 83％;for every 10 mg/L increase in RBP,the risk of kidney damage occurrence of re-nal impairment in hyperuricemia was increased by 21％;for every 0.1 mg/L increase in Cys-C,the risk of re-nal impairment occurrence in hyperuricemia was increased by 32％.Conclusion The combined diagnostic model for whether the renal impairment in the patients with hyperuricemia occurring has good diagnostic val-ue,and Cys-C deserves more attention.

According to the theory of 'Xingben Dazao' of Psoralea corylifolia Linn. (BL), the susceptible syndromes and biomarkers of liver injury caused by BL were searched. Rat models of kidney-yin deficiency syndrome (M_yin) and kidney-yang deficiency syndrome (M_yang) were established, and all animal experimental operations and welfare following the provisions of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Traditional Chinese Medicine (No. YFYDW2020017). The results showed that BL significantly decreased the body weight, water intake, and urine weight of M_yin rats and increase the organ indexes of the liver, testis, adrenal gland, and spleen and the expression of alanine aminotransferase (ALT). Meantime, BL significantly increased the urine weight of M_yang rats and decreased the expression of ALT and aspartate aminotransferase (AST). Hematoxylin and eosin (HE) staining showed that BL could aggravate inflammatory infiltration of hepatocytes in rats with M_yin and alleviate liver injury in rats with M_yang. Metabolomics identified 17 BL co-regulated significant differential metabolic markers in M_yin and M_yang rats. Among them, 8 metabolites such as glutamine, quinolinate, biliverdin, and lactosylceramide showed opposite trends, mainly involving cysteine and methionine metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, sphingolipid metabolism, glycerol phospholipid metabolism, glutamine metabolism, and other pathways. M_yin/M_yang may be the susceptible constitution of BL for liver damage or protection, which may be related to the regulation of amino acid metabolism and sphingolipid metabolism. The study can provide some experimental data support for the safe and accurate use of BL in the clinical practice of traditional Chinese medicine.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Objective:To evaluate the role of deubiquitinase OTUD1 in acute lung injury in septic mice and the relationship with transforming growth factor-beta activated kinase 1(TAK1)-mitogen-activated protein kinase (MAPK) signaling pathway.Methods:Twenty male wild-type (WT) and 20 OTUD1 gene knockout (KO) C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=10 each) using a random number table method: wild-type+ sham operation group (WT-Sham group), wild-type+ sepsis group (WT-SEP group), OTUD1-KO+ sham operation group (KO-Sham group) and OTUD1-KO+ SEP group (KO-SEP group). The acute lung injury was induced by cecal ligation and perforation (CLP) in anesthetized septic mice. Mice were sacrificed at 24 h after operation, blood samples were collected from the abdominal aorta, and lung tissues were collected. Blood gas analysis was performed using the i-STAT blood gas analyzer, PaO 2 and FiO 2 were recorded, and the oxygenation index (OI) was calculated. The morphology of lung tissues was examined with a light microscope for evaluation of lung injury, and lung injury scores were calculated. The wet to dry lung weight (W/D) ratio was measured, and the activities of MPO were measured. The concentrations of TNF-α and IL-6 in plasma were detected by enzyme-linked immunosorbent assay, and the expression of OTUD1, phosphorylated TAK1 (p-TAK1), phosphorylated p38 (p-p38), phosphorylated c-Jun amino-terminal kinase (p-JNK) and phosphorylated extracellular signal-regulated kinase (p-ERK) was detected using Western blot. Results:Compared with WT-Sham group, the PaO 2 and OI were significantly decreased, the lung injury score, W/D ratio, MPO activity, and plasma TNF-α and IL-6 concentrations were increased, and the expression of OTUD1, p-TAK1, p-p38, p-JNK and p-ERK protein in lung tissues was up-regulated in WT-SEP group ( P<0.05). Compared with WT-SEP group, the PaO 2 and OI were significantly decreased, the lung injury score, W/D ratio, MPO activity, and plasma TNF-α and IL-6 concentrations were increased, and the expression of OTUD1, p-TAK1, p-p38, p-JNK and p-ERK protein in lung tissues was up-regulated in KO-SEP group ( P<0.05). Conclusions:OTUD1 is involved in the endogenous protective mechanism against acute lung injury in septic mice, which may be related to the inhibition of TAK1-MAPK signaling pathway activation and decreased inflammatory responses.

Objective:To evaluate the role of tumor necrosis factor-alpha-induced protein-8 like-2(TIPE2) in sepsis-induced myocardial injury and the relationship with serine-threonine kinase(AKT)/glycogen synthase kinase-3β(GSK-3β)/β-catenin signaling pathway in mice.Methods:Sixteen male wild-type C57BL/6N mice and 16 TIPE2-gene knockout C57BL/6N mice, aged 6-8 weeks, with a body mass index of 20-25 g, were divided into 4 groups using a random number table method: wild-type+ sham operation group(group WT-sham), wild-type+ cecal ligation and perforation(CLP) group(group WT-CLP), TIPE2-gene knockout sham operation group(group KO-sham) and TIPE2-gene knockout CLP group(group KO-CLP), with 8 mice in each group. The model of myocardial injury induced by sepsis was developed by CLP in anesthetized animals. Blood samples from the inferior vena cava were collected at 24 h after surgery for determination of the concentrations of cardiac troponin I(cTnI) in serum by enzyme-linked immunosorbent assay. Then the mice were sacrificed and myocardial tissues were collected for determination of the pathological changes(by hematoxylin and eosin staining), expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6 mRNA(by quantitative polymerase chain reaction), and expression of TIPE2, phosphorylated AKT(p-AKT), phosphorylated GSK-3β(p-GSK-3β) and β-catenin(by Western blot).Results:Compared with the corresponding Sham groups, the serum cTnI concentration was significantly increased, the expression of TNF-α, IL-1β and IL-6 mRNA and expression of p-AKT, p-GSK-3β and β-catenin in myocardial tissues were up-regulated, the expression of TIPE2 was down-regulated( P<0.05), and the pathological changes of myocardium were found in corresponding CLP groups. Compared with group WT-CLP, the serum cTnI concentration was significantly increased, the expression of TNF-α, IL-1β and IL-6 mRNA and expression of p-AKT, p-GSK-3β and β-catenin in myocardial tissues were up-regulated, the expression of TIPE2 was down-regulated( P<0.05), and the pathological changes of myocardium were aggravated in group KO-CLP( P<0.05). Conclusions:TIPE2 reduces the myocardial injury probably through inhibiting the AKT/GSK-3β/β-catenin signaling pathway in septic mice.

Objective:To investigate the effect and role of the hepatitis B virus (HBV) on the expression of inhibin (PHB) in the proliferation and survival of hepatocellular carcinoma (HCC) cells.Methods:The expression of PHB in 13 pairs of HBV-infected livers, normal livers and HepG2.2.15 and HepG2 cells was detected by real-time fluorescent quantitative PCR and Western blot. Liver tissues were collected from seven patients with chronic hepatitis B before and after antiviral (tenofovir) treatment, and the expression of PHB was detected by RT-PCR and Western blot. HepG2.2.15 cells were transfected with Pcmv6-AC-GFP-PHB, and control vectors were collected. DNA content was analyzed by flow cytometry. The proliferation level of each cell group was detected using the EdU cell proliferation assay. HepG2.2.15 cells transfected with Pcmv6-AC-GFP-PHB and the control vector were cultured in serum-free medium for 6 days. Apoptosis was measured at the indicated time points using fluorescence-activated cell sorting (FACS)-based Annexin-V/PI double staining.Results:Compared with normal liver tissue, the expression of PHB in HBV-infected liver tissue was down-regulated ( P < 0.01). Compared with HepG2 cells, the expression of PHB in HepG2.2.15 cells was significantly decreased ( P < 0.01). The expression level of PHB in liver tissue after antiviral treatment (tenofovir) was significantly higher than that before treatment ( P < 0.01). Compared with the control vector, the proliferation rate of HepG2.2.15 cells transfected with Pcmv6-AC-GFP-PHB was significantly lower than that of the control vector, and the apoptosis rate of HepG2.2.15 cells transfected with the Pcmv6-AC-GFP-PHB vector was significantly higher than the control vector ( P < 0.01). Conclusion:HBV down-regulates the expression of inhibin to promote the proliferation and survival of hepatocellular carcinoma cells.

Background: Insulin-treated patients with long duration of type 2 diabetes mellitus (T2DM) are at increased risk of ketoacidosis related to sodium-glucose co-transporter 2 inhibitor (SGLT2i). The extent of circulating ketone elevation in these patients remains unknown. We conducted this study to compare the serum ketone response between dapagliflozin, an SGLT2i, and sitagliptin, a dipeptidyl peptidase-4 inhibitor, among insulin-treated T2DM patients. Methods: This was a randomized, open-label, active comparator-controlled study involving 60 insulin-treated T2DM patients. Participants were randomized 1:1 for 24-week of dapagliflozin 10 mg daily or sitagliptin 100 mg daily. Serum β-hydroxybutyrate (BHB) levels were measured at baseline, 12 and 24 weeks after intervention. Comprehensive cardiometabolic assessments were performed with measurements of high-density lipoprotein cholesterol (HDL-C) cholesterol efflux capacity (CEC), vibration-controlled transient elastography and echocardiography. Results: Among these 60 insulin-treated participants (mean age 58.8 years, diabetes duration 18.2 years, glycosylated hemoglobin 8.87%), as compared with sitagliptin, serum BHB levels increased significantly after 24 weeks of dapagliflozin (P=0.045), with a median of 27% increase from baseline. Change in serum BHB levels correlated significantly with change in free fatty acid levels. Despite similar glucose lowering, dapagliflozin led to significant improvements in body weight (P=0.006), waist circumference (P=0.028), HDL-C (P=0.041), CEC (P=0.045), controlled attenuation parameter (P=0.007), and liver stiffness (P=0.022). Average E/e’, an echocardiographic index of left ventricular diastolic dysfunction, was also significantly lower at 24 weeks in participants treated with dapagliflozin (P=0.037). Conclusion Among insulin-treated T2DM patients with long diabetes duration, compared to sitagliptin, dapagliflozin modestly increased ketone levels and was associated with cardiometabolic benefits.