ObjectiveChemotherapy is one of the important therapeutic approaches for cancer treatment. However, the emergence of multidrug resistance and side effects significantly limit its application. To address these challenges, chemotherapy is often combined with other drugs or therapies. Among the 13 human fucosyltransferases (FUTs) identified, FUT8 (alpha-(1,6)-fucosyltransferase) is the only enzyme responsible for core fucosylation. Core fucosylation plays an important role in cancer occurrence, metastasis and chemotherapy resistance, making the suppression of FUT8 a potential strategy for reversing multidrug resistance. This study aims to evaluate the feasibility of combining the small molecule FUT8 inhibitor 2FF (2-deoxy-2-fluoro-L-fucose) with the clinical chemotherapeutic drug doxorubicin (DOX) for treating malignant tumors. MethodsThe human hepatocellular carcinoma cell line HepG2 and mouse colon cancer cell line CT26 cells were treated with 2FF, DOX or their combination and core fucosylation levels were assessed using Lectin blot. HepG2 and CT26 cells were exposed to 50 μmol/L 2FF for 72 h, followed by treatment with a gradient concentration of DOX for 24 h. Cell viability and IC₅₀ values were determined via the CCK-8 assay. Transwell invasion assays were conducted to evaluate the combined effect of 2FF and DOX on the invasion ability of HepG2 cells. Flow cytometry was performed to analyze the impact of 2FF, DOX and their combination on membrane PD-L1 expression of HepG2 cells. To assess the in vivo effect, 6- to 8-week-old female BALB/c mice (20-25 g), were subcutaneously injected with 1×10⁶ CT26 cells into the right axilla (four groups, six mice in each group). After the average tumor volume reached 100 mm³, mice were treated with DOX, 2FF, their combination, or saline (mock group) every other day. DOX was administrated intraperitoneally (2 mg/kg), 2FF intravenously (5 mg/kg), and the combination group, received the both treatment. Tumor size was measured every other day using a vernier caliper. ResultsThis study demonstrated that DOX upregulates the core fucosylation levels in HepG2 and CT26 cells,while 2FF effectively inhibits this DOX-induced effect. Furthermone, 2FF enhanced the sensitivity of HepG2 and CT26 cells to DOX. The combination of 2FF and DOX synergistically inhibited the invasion ability of HepG2 cells, and enhanced the anti-tumor efficacy of CT26 subcutaneous tumor model in BALB/c mice. However the combination treatment led to weight loss in mice. In addition, DOX increased the cell surface PD-L1 expression in HepG2 cells, which was effectively suppressed by 2FF. ConclusionThe FUT8 inhibitor 2FF effectively suppresses DOX-induced upregulation of core fucosylation and PD-L1 levels in tumor cells, and 2FF synergistically enhances the anticancer efficacy of DOX.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To investigate the effect and mechanism of proteasome inhibitor MG132 on memory impairment induced by chronic hypoxia in mice.Methods(1)A hypoxic model of the mouse midbrain dopaminergic neuron cell line MN9D was established using a hypoxia workstation.To observe the effects of hypoxia on the expression of TH,Ub-K48 and Ub-K63,MN9D cells were divided into normoxia group and hypoxia(12 h,24 h and 48 h)groups.To observe the effects of MG132 on the expression of the above-mentioned proteins,MN9D cells were divided into normoxia group,hypoxia group and hypoxia + MG132(25,50,100,200 μmol/L)group.(2)A mouse model of memory impairment was established using a hypobaric chamber.To observe the effects of hypobaric hypoxia on the expression of TH,Ub-K48 and Ub-K63 in the substantia nigra compacta(SNc)of mice,thirty C57BL/6 mice were randomly and equally divided into normoxia group and hypobaric hypoxia(3 d and 21 d)groups,10 in each group.To observe the effects of MG132 on spatial memory impairment induced by hypobaric hypoxia,twenty-four C57BL/6 mice were randomly and equally divided into normoxia group,hypobaric hypoxia 21 d group and hypobaric hypoxia 21 d+MG132 group,8 in each group.(3)The protein expression levels of TH,Ub-K48,and Ub-K63 in MN9D cells which were either subjected to different durations of hypoxia treatment or pre-treated with MG132 prior to hypoxia treatment were detected using Western blotting(WB).The novel object recognition test was used to detect the memory function of mice.Immunofluorescence was used to detect the proportion of positive immunoreactive area of TH response in the SNc region.The expression levels of TH,Ub-K48,and Ub-K63 in the SNc region were detected by WB.Results(1)Compared with normoxia group,MN9D cells in hypoxia 24 h group showed increasing expression of Ub-K48 and Ub-K63(P<0.05),and decreasing expression of TH(P<0.05),and MN9D cells in all hypoxia groups showed increasing expression of Ub-K48/TH and Ub-K63/TH(P<0.05).Compared with hypoxia group,MN9D cells showed decreasing expression of Ub-K48/TH and Ub-K63/TH in hypoxia + MG132 100 umol/L group and hypoxia + MG132 200 umol/L group(P<0.05).(2)Compared with the mice in normoxia group,mice in 3 d and 21 d hypobaric hypoxia groups showed decreasing expression of TH(P<0.001),and increasing expression of Ub-K48/TH and Ub-K63/TH(P<0.05)in the SNc region.Compared with normoxia group,the mice in 21 d hypobaric hypoxia group showed a lower new object recognition index(P<0.01),and the proportion of positive immunoreactive area of TH response in the SNc region(P<0.05).Compared with 21 d hypobaric hypoxia group,the mice in hypobaric hypoxia 21 d+MG132 group showed a higher new object recognition index(P<0.01).Conclusion The proteasome inhibitor MG132 could alleviate the memory impairment induced by chronic hypoxia in mice,and its mechanism may be related to the inhibition of Ub-K63 and Ub-K48,which in turn upregulates expression of TH in dopaminergic neurons.

Background and aim:Hepatic ischemia-reperfusion injury(IRI)is a significant challenge in liver trans-plantation,trauma,hypovolemic shock,and hepatectomy,with limited effective interventions available.This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2(LECT2)in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA(shRNA)delivered through adeno-associated virus(AAV)vectors. Materials and methods:This study analyzed human liver and serum samples from five patients under-going the Pringle maneuver.Lect2-knockout and C57BL/6J mice were used.Hepatic IRI was induced by clamping the hepatic pedicle.Treatments included recombinant human LECT2(rLECT2)and AAV-Lect2-shRNA.LECT2 expression levels and serum biomarkers including alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine,and blood urea nitrogen(BUN)were measured.Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed. Results:Serum and liver LECT2 levels were elevated during hepatic IRI.Serum LECT2 protein and mRNA levels increased post reperfusion.Lect2-knockout mice had reduced weight loss;hepatic necrosis;and serum ALT,AST,creatinine,and BUN levels.rLECT2 treatment exacerbated weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN).AAV-Lect2-shRNA treatment significantly reduced weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN),indicating thera-peutic potential. Conclusions:Elevated LECT2 levels during hepatic IRI increased liver damage.Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage,indicating its therapeutic potential.AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI,offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To observe the value of semi-quantitative parameters related to gated myocardial perfusion imaging(G-MPI)for predicting occurrence of major adverse cardiovascular events(MACE)in patients with chronic kidney disease(CKD).Methods Totally 148 CKD patients who underwent rest G-MPI(R-GMPI)(R-GMPI group,n=95)or stress/rest G-MPI(S/R-GMPI)(S/R-GMPI group,n=53)were retrospectively included.The patients were categorized into MACE subgroup and non-MACE subgroup according to MACE occurred or not during follow-up.Clinical data and G-MPI parameters were compared between subgroups,and independent predictors of MACE in CKD patients were obtained using multivariate Cox proportional hazards regression analysis.Receiver operating characteristic(ROC)curve was drawn,the area under the curve(AUC)was calculated to assess the efficacy of each independent predictor for predicting MACE.Among patients who underwent only R-GMPI,the optimal cut-off value of each parameter for predicting MACE was obtained by ROC curve analysis,and the risk of MACE was stratified,then Kaplan-Meier curves were drawn and compared with log-rank test.Results Among 95 patients who underwent only R-GMPI,compared with non-MACE subgroup,those in MACE subgroup had smaller body mass index(BMI)and higher proportion of previous myocardial infarction and hemodialysis,as well as higher R-GMPI left ventricle end-diastolic volume(R-LVEDV),left ventricle end-systolic volume(R-LVESV),sum rest score(R-SRS)but lower left ventricle ejection fraction(R-LVEF)(all P＜0.05),while R-SRS(HR=1.068,95％CI[1.027,1.110])and R-LVESV(HR=1.011,95％CI[1.005,1.017])were both independent predictors for MACE(both P＜0.05).Among 53 patients who underwent S/R-GMPI,compared with non-MACE subgroup,those in MACE subgroup had with higher blood creatinine and lower estimated glomerular filtration rate(eGFR),higher S-LVESV,R-LVEDV,sum stress score(SSS),SRS and sum difference score(SDS)(all P＜0.05),and SDS(HR=1.454,95％CI[1.063,1.989])was an independent predictor for MACE(P＜0.05).Among 95 CKD patients who underwent only R-GMPI,AUC of R-SRS and R-LVESV alone for predicting MACE was 0.659 and 0.694,respectively,and higher incidence of MACE was found in those w ith R-SRS ≥8 points,also in those with R-LVESV ≥91 ml(both P＜0.05).Conclusion G-MPI could be used to evaluate myocardial perfusion and function in CKD patients.For CKD patients just underwent only R-GMPI,R-SRS and R-LVESV were independent predictors for MACE,whereas SDS might be utilized to predict MACE in CKD patients who could undergo S/R-GMPI.

Objective:To evaluate the predictive value of stress+ rest gated myocardial perfusion imaging (G-MPI) in assessing all-cause mortality risk in patients with familial hypercholesterolemia (FH).Methods:From June 2010 to March 2022, 72 patients (39 males, 33 females; age (21.1±12.3) years) who diagnosed with FH clinically and genetically and underwent stress+ rest G-MPI in Beijing Anzhen Hospital, Capital Medical University were retrospectively followed up. Image analysis was performed using the 17-segment 5-point method to obtain left ventricular myocardial perfusion and functional parameters. Patients were followed for all-cause mortality events, and predictors associated with the risk of all-cause mortality were analyzed using Cox regression. The efficiencies of predictors were evaluated by ROC curve analysis, and the Kaplan-Meier method and log-rank test were used to compare the differences in the incidence of all-cause mortality in different groups of patients with FH. Independent-sample t test or Mann-Whitney U test was used to analyze the data. Results:The follow-up time of 72 patients was 7(4, 10) years, and all-cause death occurred in 16(22.2%) patients during the follow-up period. There were statistically significant differences in total cholesterol (TC), low density lipoprotein cholesterol (LDLC), summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), stress end-systolic volume (SESV), stress ejection fraction (SEF), rest end-diastolic volume (REDV), rest end-systolic volume (RESV) and rest ejection fraction (REF) between the death group and the survival group ( t values: from -2.65 to 4.47, z values: from -3.43 to -1.98, all P<0.05). Cox regression analysis showed that SDS (hazard ratio ( HR)=1.337, 95% CI: 1.114-1.604, P=0.002), SESV ( HR=1.019, 95% CI: 1.008-1.030, P<0.001) and LDLC ( HR=1.355, 95% CI: 1.049-1.749, P=0.020) were independent predictors associated with the risk of all-cause mortality in patients with FH. The optimal cut-off value of SESV for predicting mortality in patients with FH determined by ROC curve analysis was 35.5 ml, with the AUC of 0.701 (95% CI: 0.517-0.885). The incidence of all-cause mortality in the group with SESV≥35.5 ml was significantly higher than that in the group with SESV<35.5 ml (28.6% vs 6.9%; χ2=5.15, P=0.023). Conclusion:Stress+ rest G-MPI is an important imaging method for all-cause mortality risk assessment in patients with FH, and SDS, SESV and LDLC are important factors in predicting mortality in patients with FH.

Diabetic retinopathy(DR)is the main cause of substantial visual impairment of occupational active individuals in the world, which has become one of the most common eye diseases that lead to irreversible visual impairment of the working population. Precise identification and accurate intervention of early DR lesions are of great significance to block or delay the development of this disease. Recent studies have shown that DR nerve injury occurs before retinal microangiopathy, it has a series of characteristic clinical manifestations, such as dark adaptation delay, contrast sensitivity and decreased tone discrimination. These characteristic clinical manifestations are key events in the early stage of DR, which are closely related to apoptosis, glial cell proliferation, oxidative stress, inflammation, excitotoxicity of glutamate and imbalance of neurotrophic factors. In this paper, the research progress of DR nerve damage and its related factors are reviewed in order to provide new ideas for the prevention and treatment of DR.

To explore the digital manufacturing process of distal extension removable partial denture. From November 2021 to December 2022, 12 patients (7 males and 5 females) with free-ending situation were selected from the Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University. Three-dimensional model of the relationship between alveolar ridge and jaw position was obtained by intraoral scanning technique. After routine design, manufacturing and try-in of metal framework for removable partial denture, the metal framework was located in the mouth and scanned again to obtain the composite model of dentition, alveolar ridge and metal framework. The free-end modified model is obtained by merging the digital model of free-end alveolar ridge with the virtual model with the metal framework. The three-dimensional model of artificial dentition, and base plate was designed on the free-end modified model, and the resin model were made by digital milling technology. The removable partial denture was made by accurately positioning the artificial dentition and base plate, bonding metal framework with injection resin, grinding and polishing the artificial dentition and resin base. Compared with the design data after clinical trial, the results showed that there was an error of 0.4-1.0 mm and an error of 0.03-0.10 mm in the connection between the resin base of artificial dentition and the connecting rod of the in-place bolt and the connection between artificial dentition and resin base. After denturen delivery, only 2 patients needed grinding adjustment in follow-up visit due to tenderness, and the rest patients did not find any discomfort. The digital fabrication process of removable partial denture used in this study can basically solve the problems of digital fabrication of free-end modified model and assembly of artificial dentition with resin base and metal framework.

Objective: To document the anatomical structure of the area anterior to the anorectum passing through the levator hiatus between the levator ani slings bilaterally. Methods: Three male hemipelvises were examined at the Laboratory of Clinical Applied Anatomy, Fujian Medical University. (1) The anatomical assessment was performed in three ways; namely, by abdominal followed by perineal dissection, by examining serial cross-sections, and by examining median sagittal sections. (2) The series was stained with hematoxylin and eosin to enable identification of nerves, vessels, and smooth and striated muscles. Results: (1) It was found that the rectourethralis muscle is closest to the deep transverse perineal muscle where the longitudinal muscle of the rectum extends into the posteroinferior area of the membranous urethra. The communicating branches of the neurovascular bundle (NVB) were identified at the posterior edge of the rectourethralis muscle on both sides. The rectum was found to be fixed to the membranous urethra through the rectourethral muscle, contributing to the anorectal angle of the anterior rectal wall. (2) Serial cross-sections from the anal to the oral side were examined. At the level of the external anal sphincter, the longitudinal muscle of the rectum was found to extend caudally and divide into two muscle bundles on the oral side of the external anal sphincter. One of these muscle bundles angled dorsally and caudally, forming the conjoined longitudinal muscle, which was found to insert into the intersphincteric space (between the internal and external anal sphincters). The other muscle bundle angled ventrally and caudally, filling the gap between the external anal sphincter and the bulbocavernosus muscle, forming the perineal body. At the level of the superficial transverse perineal muscle, this small muscle bundle headed laterally and intertwined with the longitudinal muscle in the region of the perineal body. At the level of the rectourethralis and deep transverse perineal muscle, the external urethral sphincter was found to occupy an almost completely circular space along the membranous part of the urethra. The dorsal part of the external urethral sphincter was found to be thin at the point of attachment of the rectourethralis muscle, the ventral part of the longitudinal muscle of the rectum. We identified a venous plexus from the NVB located close to the oral and ventral side of the deep transverse perineal muscle. Many vascular branches from the NVB were found to be penetrating the longitudinal muscle and the ventral part of rectourethralis muscle at the level of the apex of the prostate. The rectourethral muscle was wrapped ventrally around the membranous urethra and apex of the prostate. The boundary between the longitudinal muscle and prostate gradually became more distinct, being located at the anterior end of the transabdominal dissection plane. (3) Histological examination showed that the dorsal part of the external urethral sphincter (striated muscle) is thin adjacent to the striated muscle fibers from the deep transverse perineal muscle and the NVB dorsally and close by. The rectourethral muscle was found to fill the space created by the internal anal sphincter, deep transverse perineal muscle, and both levator ani muscles. Many tortuous vessels and tiny nerve fibers from the NVB were identified penetrating the muscle fibers of the deep transverse perineal and rectourethral muscles. The structure of the superficial transverse perineal muscle was typical of striated muscle. These findings were reconstructed three-dimensionally. Conclusions: In intersphincteric resection or abdominoperineal resection for very low rectal cancer, the anterior dissection plane behind Denonvilliers' fascia disappears at the level of the apex of the prostate. The prostate and both NVBs should be used as landmarks during transanal dissection of the non-surgical plane. The rectourethralis muscle should be divided near the rectum side unless tumor involvement is suspected. The superficial and deep transverse perineal muscles, as well as their supplied vessels and nerve fibers from the NVB. In addition, the cutting direction should be adjusted according to the anorectal angle to minimize urethral injury.
Humans ; Male ; Rectum/surgery* ; Anal Canal/anatomy & histology* ; Rectal Neoplasms/surgery* ; Proctectomy ; Urethra/surgery*