Objective To investigate the mechanism by which human umbilical cord mesenchymal stem cells-derived exosomes(hucMSCs-exos) improve hepatic insulin resistance(IR) in rats with type 2 diabetes mellitus(T2DM).Methods Male Wistar rats were divided into control, T2DM and hucMSCs-exo groups, with 8 rats in each group. The rats in T2DM group were fed with high-fat diet for 40 days, and then injected with streptozotocin(30 mg/kg) intraperitoneally for modeling. The oral glucose tolerance test(OGTT) was performed 7 days after modeling to verify the model. Treatment regimen: Rats in the control and T2DM groups were injected with 0. 4 mL PBS buffer via the tail vein, and rats in the hucMSCs-exo group were injected with hucMSCs-exo(3 mg/kg, dissolved in 0. 4 mL PBS buffer) via the tail vein for a total of 4 injections at an interval of 1 week. An automatic biochemical analyzer was used to measure the levels of triglyceride(TG), total cholesterol(TC), high density lipoprotein(HDL), low density lipoprotein(LDL) and free fatty acids(FFAs). The pathological changes in the liver were assessed by HE staining. The expression levels of genes and proteins involved in lipid metabolism and insulin signaling,including downstream of tyrosine kinase 1(Dok1), insulin receptor substrate 1/2(Irs1/2), phosphatidylinositol 3-kinase(Pi3k),protein kinase B(Akt) and sterol regulatory element binding protein-1c(Srebp1c) were determined by qPCR and Western blot.Results Compared to the T2DM group, fasting blood glucose was significantly reduced in the hucMSCs-exo group after day 24(day 24: P = 0. 010 9; day 28: P = 0. 005 4). Fasting blood glucose, 90-minute, and 120-minute postprandial glucose levels were significantly reduced after treatment(P = 0. 002 1, 0. 002 9 and < 0. 000 1, respectively). HucMSCs-exo treatment also reduced the levels of LDL and FFAs in T2DM rats(P = 0. 011 3 and 0. 002 5, respectively). The treatment reduced hepatic steatosis in T2DM rats, significantly increased the expression of Dok1 and Akt(each P < 0. 000 1) and reduced the expression of Srebp1c(P = 0. 031 5). The treatment upregulated the expression of DOK1 and p-AKT/AKT(P = 0. 024 1 and <0. 000 1, respectively), and significantly downregulated the expression of SREBPLC(P < 0. 000 1).Conclusion HucMSCsexos reduce hepatic lipid ectopic accumulation by upregulating DOK1, thereby restoring hepatic insulin sensitivity,normalizing hepatic lipid metabolism, and ameliorating the progression of T2DM.

Primary liver cancer is one of the most common malignant tumors of the digestive system， and the “inflammation-to-cancer transformation” （ICT） of chronic hepatitis is the core pathological process of the progression of chronic hepatitis to liver cancer. Persistent and uncontrolled liver inflammation in patients with chronic hepatitis often leads to repeated liver tissue damage and repair， which gradually develops into liver fibrosis and cirrhosis， eventually leading to malignant transformation through the mechanisms such as gene mutation and microenvironment imbalance. ICT in chronic hepatitis is the key link between chronic hepatitis and liver cancer， and its dynamic evolution involves various pathogenic factors such as dampness， heat， deficiency， toxin， and stasis； among which damp-heat and vital energy deficiency are the initiating factors for ICT of chronic hepatitis， while intermingled stasis and toxin are the key pathological products that promote malignant transformation. Based on the concept of preventive treatment， traditional Chinese medicine can effectively delay and even block the ICT of chronic hepatitis by regulating inflammation， metabolism， and abnormal cell proliferation through multiple targets， which provides important strategies and research directions for the prevention and treatment of liver cancer.

Chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) are both chronic progressive respiratory diseases that cannot be completely cured. COPD is characterized by irreversible airflow limitation, chronic airway inflammation, and gradual decline in lung function, whereas PH is characterized by pulmonary vasoconstriction, remodeling, and infiltration of inflammatory cells. These diseases have similar pathological features, such as vascular hyperplasia, arteriolar contraction, and inflammatory infiltration. Despite these well-documented observations, the exact mechanisms underlying the occurrence and development of COPD and PH remain unclear. Evidence that mitochondrial dynamics imbalance is one major factor in the development of COPD and PH. Mitochondrial dynamics is precisely regulated by mitochondrial fusion proteins and fission proteins. When mitochondrial dynamics equilibrium is disrupted, it causes mitochondrial and even cell morphological dysfunction. Mitochondrial dynamics participates in various pathological processes for heart and lung disease. Mitochondrial dynamics may be different in the early and late stages of COPD and PH. In the early stages of the disease, mitochondrial fusion increases, inhibiting fission, and thereby compensatorily increasing adenosine triphosphate (ATP) production. With the development of the disease, mitochondria decompensation causes excessive fission. Mitochondrial dynamics is involved in the development of COPD and PH in a spatiotemporal manner. Based on this understanding, treatment strategies for mitochondrial dynamics abnormalities may be different at different stages of COPD and PH disease. This article will provide new ideas for the potential treatment of related diseases.
Humans ; Mitochondrial Dynamics/physiology* ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Hypertension, Pulmonary/metabolism* ; Mitochondria/metabolism* ; Animals

Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.
Humans ; Uric Acid/metabolism* ; Stroke/drug therapy* ; Animals ; Hyperuricemia/drug therapy* ; Ischemic Stroke/blood* ; Biomarkers/blood*

Objective To discuss the correlation between free prostate specific antigen(fPSA),serum ferritin(SF),blood uric acid(SUA)levels and Gleason grading in patients with prostate cancer(PCa).Methods The clinical data of 61 patients with prostate biopsy treated in 411 Hospital of Shanghai University from January to December of 2023 were retrospectively analyzed.According to the results of puncture,the patients were divided into benign prostatic hyperpla-sia(BPH)group(31 cases)and PCa group(30 cases).The levels of fPSA,SF and SUA in patients and Gleason grade in biopsy cases were analyzed.The correlation between fPSA,SF and SUA levels and Gleason grade was analyzed by the method of Spearman.And the diagnostic efficacy of fPSA,SF and SUA levels on PCa was analyzed by receiver operating characteristic curve(ROC).Results The levels of fPSA,SF and SUA in PCa group were significantly higher than those in BPH group(P＜0.05).There were statistically significant differences in levels of fPSA SF and SUA in PCA patients with different Gleason grades(P＜0.05).With the specificity reaching 96.08％and sensitivity reaching 94.35％,the ar-ea under the curve(AUC)of the combined fPSA,SF and SUA levels in the diagnosis of PCa was 0.982,which was higher than that of the single fPSA,SF and SUA levels(P＜0.05).SF and SUA levels in PCa patients were positively correlated with Gleason grade(P＜0.05),while fPSA levels were not correlated with Gleason grade(P＞0.05).Conclusion The levels of SF and SUA in PCa patients are positively correlated with Gleason grade,which can be used as an important index to predict Gleason grade in PCa patients.

Objective:To explore the differences in resting-state brain functional activity in obsessive-compulsive disorder (OCD) patients with and without sensory phenomena (SP).Methods:Clinical data from 102 OCD patients (60 males, 42 females; age 18-50(27±8) years) who visited the OCD outpatient clinic at the Affiliated Brain Hospital of Nanjing Medical University between August 2021 and December 2022 were prospectively collected. Based on the presence of sensory phenomena, patients were categorized into 70 cases with sensory phenomena (Sensory Phenomena Group) and 32 cases without sensory phenomena (Non-Sensory Phenomena Group). Additionally, 50 age-matched healthy controls (Control Group, 24 males, 26 females; age 18-49(25±6) years) were recruited. Resting-state functional magnetic resonance imaging (rs-fMRI) was analyzed using the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) between differential brain regions. One-way ANOVA and post-hoc tests were used to compare group differences. Spearman correlation and binary logistic stepwise regression were applied to analyze the associations between SP and brain functional activity.Results:Compared to healthy controls, OCD patients showed decreased ALFF in bilateral middle frontal gyri, left superior frontal gyrus, right angular gyrus, and right supramarginal gyrus ( F=17.29-32.99, all P<0.05). The SP group exhibited increased ALFF in the right triangular part of the inferior frontal gyrus ( F=23.47, P<0.05) and decreased ALFF in the left superior parietal gyrus and left postcentral gyrus ( F=18.80, 15.04; both P<0.05). The non-SP group demonstrated increased ALFF in the left supramarginal gyrus and left postcentral gyrus ( F=19.64, 15.04; both P<0.05) and decreased ALFF in the left superior frontal gyrus, right middle frontal gyrus, and left angular gyrus ( F=17.29-35.52, all P<0.05). Reduced FC was observed between the left middle frontal gyrus and left angular gyrus, left middle frontal gyrus and right angular gyrus and left and right angular gyri ( F=17.29-23.47, all P<0.05). The SP group showed lower FC between the left middle frontal and left angular gyrus than the non-SP group ( F=23.47, P<0.05). Positive correlations with SP were found for ALFF in the right triangular part of the inferior frontal gyrus, left superior frontal gyrus, and right middle frontal gyrus (r=0.40, 0.35, 0.31; all P<0.05). Negative correlations were observed for ALFF in the left supramarginal gyrus, left superior parietal gyrus, and left postcentral gyrus (r=-0.38, -0.47, -0.52; all P<0.05) and FC between the left middle frontal gyrus-left angular gyrus and left middle frontal gyrus-right angular gyrus (r=-0.24, -0.21; both P<0.05). OCD patients with increased ALFF in the left superior frontal gyrus and right middle frontal gyrus, along with decreased ALFF in the left supramarginal gyrus, left superior parietal gyrus, left postcentral gyrus, and reduced FC between the left middle frontal gyrus-right angular gyrus, had a higher likelihood of SP (log OR (95% CI)=8.5(4.0-14.2), 8.0(1.7-16.4), -8.9(-15.2--4.4), -5.2 (-9.1--2.3), -4.1(-6.9--1.7), -7.0(-13.2--1.8); all P<0.05). Conclusion:Altered functional activity in the left superior frontal gyrus, right middle frontal gyrus, left supramarginal gyrus, left superior parietal gyrus, left postcentral gyrus, and abnormal FC between the left middle frontal gyrus and right angular gyrus represent key neuroimaging features of OCD patients with SP.

OBJECTIVES: The objective of this study is to measuring the morphology and position of bilateral temporomandibular joints in patients with unilateral and bilateral molar scissor bite and simulating the deformation of the mandible during occlusion, in order to provide thesis for the diagnosis of temporomandibular joint disease in patients with unilateral and bilateral molar scissor bite. METHODS: This study was a retrospective study. A total of 10 patients with unilateral molar scissor bite (the unilateral molar scissor bite group) and 10 patients with bilateral molar scissor bite (the bilateral molar scissor bite group) were selected as the experimental group, and 20 adult patients with classⅠ of angle classification of similar ages were selected as the control group. All patients underwent cone beam computed tomography scans, by measuring the width of the fossa, height of the fossa, articular eminence inclination, long axis of the condyle, minor axis of the condyle, horizontal angle of the condyle and the space of the temporomandibular joint, compare temporomandibular joint morphology and position. The three-dimensional finite element analysis of the mandible morphology was carried out to evaluate the force and deformation of the mandible by using software to simulate the occlusion of the patients. It was further explored the relationship between the force of the mandible morphology and the possible temporomandibular joint disorder symptoms of the patients. RESULTS: Intergroup comparisons for the unilateral molar scissor bite group and left sides of the other groups revealed that the superior articular space in the group with unilateral molar scissor bite was shorter than that in the control group (P<0.05); the long axis of the condyle in the unilateral and bilateral molar scissor bite group were both shorter than that of the control group (P<0.05); among which the unilateral group was larger than the bilateral group, and the minor axis of the condyle in bilateral molar scissor bite group was smaller than in the control group (P<0.05), and the unilateral and bilateral condylar groups were larger than the control group (P<0.05); and the condylar horizontal angle in the unilateral and bilateral groups were larger than that in the control group (P<0.05). The normal sides of the unilateral molar scissor bite group and right sides of the other groups had smaller superior articular space than the control group (P<0.05); and the condylar long-axis in bilateral group was smaller than the control group (P<0.05); and the normal side of the condylar short-axis unilateral group was larger than that of the bilateral condylar group. Three-dimensional finite element analysis: the condyle of patients with molar scissor bite was a concentrated area of deformation during the bite of the mandible, when the first molar occlusion of the scissors bite side was simulated, the maximum deformation was located in the condyle in the X-axis and Z-axis directions. The amount of deformation was greater than that of the scissor bite side in the X-axis direction, while in the Z-axis direction, the normal side was greater than the scissor bite side. The maximum sites of local deformation in the X-axis direction were located in anterior and posterior the transverse crest of scissor bite side, and the minimum sites of local deformation was at 1/3 of the anterior slope of the inner pole of the normal side, the maximum local deformation sites in the Z-axis direction were located in the outer pole and below the outer pole of the normal side. The X-axis deformation value was the largest in the molars occlusion on the normal side, the Y-axis deformation value was in the premolars occlusion on the normal side, and the Z-axis deformation value was the largest in the centric occlusion, the deformation value of the condyle was not most significant in molar scissor bite. CONCLUSIONS Unilateral and bilateral molar scissor bite resulting in a short condyle morphology, and the bilateral group had a shorter condylar morphology than the unilateral group. The condyle of the patient with molar scissor bite is a concentrated area of poor occlusal deformation, and the largest sites of deformation are distributed near the transverse ridge of the inner and outer poles of the condyle. Different occlusion conditions have an effect on condylar deformation values, but do not indicate whether there is a clear association between them.
Humans ; Finite Element Analysis ; Retrospective Studies ; Temporomandibular Joint/pathology* ; Cone-Beam Computed Tomography ; Mandible/pathology* ; Imaging, Three-Dimensional ; Adult ; Temporomandibular Joint Disorders/diagnostic imaging* ; Mandibular Condyle/diagnostic imaging* ; Female ; Male ; Molar

Objective:To compare the curative effect of local anesthesia Lichtenstein, modified Kugel and general anesthetic transabdominal preperitoneal(TAPP) hemioplasty in the treatment of primary unilateral inguinal hernia in elderly patients.Methods:Six hundred and twenty-one patients with unilateral primary inguinal hernia admitted at Second Hospital of Tianjin Medical University from January 2021 to December 2023 were randomly divided into 3 groups before operation: Lichtenstein group, Modified-Kugel group, TAPP group,207 patients in each group. The clinical data were compared.Results:The average operation time of the Lichtenstein and modified Kugel hernia repair groups was significantly shorter than that of TAPP group ( P<0.01), and the hospitalization cost was also significantly lower than that of TAPP group. The postoperative pain score, time spent in the ground and hospital stay in TAPP group were significantly lower than those in Lichtenstein and modified Kugel groups ( P<0.05). There were no serious complications in the 3 groups. Conclusions:Three kinds of hernia repair are all safe and effective in the treatment of elderly patients with unilateral primary inguinal hernia. TAPP has lighter postoperative pain and quicker recovery. Lichtenstein and Modified-Kugel hernia repair under local anesthesia are suitable for those who cannot tolerate general anesthesia.

Background and Aims:Currently,the treatment of hepatocellular carcinoma(HCC)faces significant challenges due to recurrence and metastasis,with tumor immune evasion being one of the key mechanisms underlying these issues.Signal transducer and activator of transcription 3(STAT3),an important transcription factor,is overactivated in many malignancies and is involved in both tumorigenesis and progression,closely associated with immune evasion.Programmed cell death ligand 1(PD-L1),a key immune checkpoint,helps tumor cells evade immune surveillance when its expression is upregulated,thereby suppressing anti-tumor immunity.Studies have shown that STAT3 may activate the MYC signaling pathway through interaction with DNA-activated protein kinase(PRKDC),thereby promoting PD-L1 expression and inducing immune evasion.However,the specific mechanism of the STAT3/PRKDC/MYC axis in HCC remains unclear.This study aims to elucidate the molecular mechanism by which STAT3 regulates PD-L1 expression through the PRKDC/MYC signaling pathway,potentially inducing immune evasion in HCC,with the goal of providing potential targets for HCC immunotherapy.Methods:The expressions of STAT3 in human normal liver cells(HL-7702)and human HCC cells(HuH-7,HepG2)were detected by qRT-PCR and Western blot.Plasmids with STAT3 knockdown(si-STAT3)and PRKDC overexpression(oe-PRKDC),along with their respective negative controls(si-NC,oe-NC),were constructed and transfected into HCC cells(HuH-7)according to the experimental design,with untreated HuH-7 cells as the blank control.Western blot was used to analyze the expression of STAT3,PRKDC,PD-L1,and MYC pathway-related proteins.Cell proliferation,invasion,migration,and apoptosis of HCC cells were assessed by CCK-8,Transwell,wound healing assay,and flow cytometry.After co-culturing HuH-7 cells with human peripheral blood mononuclear cells(hPBMCs),ELISA was used to detect the secretion of the immune regulatory factor interferon γ(IFN-γ).Co-immunoprecipitation and immunofluorescence co-localization were performed to verify the interaction between STAT3 and PRKDC proteins.Results:Results of qRT-PCR and Western blot showed that the mRNA and protein levels of STAT3 were significantly elevated in HCC cells(both P＜0.05).Functional experiments demonstrated that in the si-STAT3 group,HCC cell proliferation,migration,and invasion were significantly weakened,and cell apoptosis was notably increased;the expression of PD-L1 and MYC pathway-related proteins was significantly downregulated;the secretion of IFN-γ was significantly increased after co-culturing with hPBMCs(all P＜0.05).After co-culturing with oe-PRKDC plasmids,the effects of STAT3 knockdown on HCC cells were significantly reversed(all P＜0.05).Scansite 4.0 database analysis revealed that STAT3 and PRKDC have binding sites,and co-immunoprecipitation and immunofluorescence co-localization experiments confirmed the interaction between STAT3 and PRKDC proteins.Conclusion:STAT3 is highly expressed in HCC cells and can promote HCC cell proliferation,migration,invasion,and immune evasion through interaction with PRKDC,suppress cell apoptosis,activate the MYC pathway,and increase PD-L1 expression.The STAT3/PRKDC/MYC axis may serve as a potential target for HCC immunotherapy.

Objective To compare the clinical efficacy of laparoscopic high ligation of the hernia sac combined with intraperitoneal onlay mesh(IPOM)and local anesthesia Lichtenstein repair for the treatment of inguinal hernia after total cystectomy in male patients.Methods A total of 59 male patients who underwent total cystectomy were included in this study and randomly divided into two groups:the laparoscopic high ligation of the hernia sac combined with IPOM group(IPOM group,30 cases)and the local anesthesia Lichtenstein repair group(local anesthesia group,29 cases).The patient age,surgical time,postoperative ambulation time,visual analogue scale score for pain on the 1st to 3rd days and 3 months after operation,time to first mobilization post-operation,pain scores on postoperative day 1,2 and 3,pain scores at 3 months post-operation were observed and compared between the two groups.Data of intraoperative blood loss,hospital stay,time to return to daily activities,total surgery costs,recurrence rates at 1 year after operation and complications were also observed and compared in two groups of patients.The results were analyzed to determine the optimal surgical method.Results The IPOM group demonstrated better outcomes in terms of surgical time,time to first mobilization,pain scores on postoperative days 1,2 and 3,pain scores at 3 months,intraoperative blood loss,hospital stay and time to return to daily activities compared to those of the local anesthesia group(P＜0.01).However,the total cost of the operation was higher in the IPOM group than those of the local anesthesia group(P＜0.01).There were no significant differences in postoperative complications between the two groups(P＞0.05).The recurrence rate of the IPOM group one year after surgery was better than that of the local anesthesia group(P＜0.05).Conclusion Laparoscopic IPOM with high ligation of the hernia sac is superior to the traditional Lichtenstein repair in reducing postoperative pain and recurrence rates.This surgical method should be the first choice when economic conditions permit.