Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults.The high levels of glucose trigger multiple intracellular oxidative stress pathways,such as POLDIP2,resulting in excessive reactive oxygen species(ROS)pro-duction and increased expression of vascular cell adhesion molecule-1(VCAM-1),hypoxia-inducible factor 1α(HIF-1α),and vascular endothelial growth factor(VEGF),causing microvascular dysfunction.Dihydromyricetin(DMY)is a natural flavonoid small molecule antioxidant.However,it exhibits poor solubility in physiological environments,has a short half-life in vivo,and has low oral bioavailability.In this study,we present,for the first time,the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles(Fe-DMY NCPs),formed by combining DMY with low-toxicity iron ions.In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endo-thelial cells by high glucose,scavenge excess ROS,and improve pathological features of DR,such as retinal vascular leakage and neovascularization.Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H2O2 signaling pathway and downregulate vital vascular function indicators such as VCAM-1,HIF-1α,and VEGF.These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent,with the potential as a novel multimeric drug for DR therapy.

Objective: To examine the clinical feasibility of mixed reality navigation (MRN) technology based on multimodal imaging for the resection of intracranial eloquent lesions. Methods: Fifteen patients with intracranial eloquent lesions admitted to the Department of Neurosurgery, the First Medical Center, People's Liberation Army General Hospital from September 2020 to September 2021 were retrospectively enrolled. There were 7 males and 8 females, aged (50±16) years (range: 16 to 70 years). Postoperative pathological diagnosis included meningioma (n=7), metastatic carcinoma (n=3), cavernous hemangioma, glioma, ependymoma, aneurysmal changes and lymphoma (n=1, respectively). The open-source software was used to perform the three-dimensional visualization of preoperative images, and the self-developed MRN system was used to perform the fusion and interaction of multimodal images, so as to formulate the surgical plan and avoid damaging the eloquent white matter fiber tracts. Traditional navigation, intraoperative ultrasound and fluorescein sodium angiography were used to determine the extent of lesion resection. The intraoperative conditions of MRN-assisted surgery were analyzed, and the setup time and localization error of MRN system were measured. The changes of postoperative neurological function were recorded. Results: MRN based on multimodal imaging was achieved in all patients. The MRN system setup time (M(IQR)) was 36 (12) minutes (range: 20 to 44 minutes), and the localization error was 3.2 (2.0) mm (range: 2.6 to 6.7 mm). The reliability of eloquent white matter fiber tracts localization based on MRN was rated as "excellent" in 11 cases, "medium" in 3 cases, and "poor" in 1 case. There were no perioperative death and no new impairment in motor, language, or visual functions after operation. Transient limb numbness occurred in 1 patient after operation, and recovered to the preoperative state in 2 weeks after operation. Conclusion: The MRN system based on multimodal imaging can improve the surgical accuracy and safety, and reduce the incidence of iatrogenic neurological dysfunction.
Humans ; Augmented Reality ; Reproducibility of Results ; Retrospective Studies ; Multimodal Imaging

Objective: To investigate hypertriglyceridemia and hepatomegaly caused by Schisandrae Sphenantherae Fructus (FSS) and Schisandra chinensis Fructus (FSC) oils in mice. Methods: Mice were orally administered a single dose of Schisandrae Fructus oils. Serum and hepatic triglyceride (TG), triglyceride transfer protein (TTP), apolipoprotein B48 (Apo B48), very-low-density lipoprotein (VLDL), hepatocyte growth factor (HGF), alanine aminotransfease (ALT) and liver index were measured at 6-120 h post-dosing. Results: FSS and FSC oil caused time and dose-dependent increases in serum and hepatic TG levels, with maximum increases in the liver (by 297% and 340%) at 12 h post-dosing and serum (244% and 439%) at 24-h post-dosing, respectively. Schisandrae Fructus oil treatments also elevated the levels of serum TTP by 51% and 63%, Apo B48 by 152% and 425%, and VLDL by 67% and 38% in mice, respectively. FSS and FSC oil treatments also increased liver mass by 53% and 55% and HGF by 106% and 174%, but lowered serum ALT activity by 38% and 22%, respectively. Fenofibrate pre/ co-treatment attenuated the FSS and FSC oil-induced elevation in serum TG levels by 41% and 49% at 48 h post-dosing, respectively, but increased hepatic TG contents (by 38% and 33%, respectively) at 12 h post-dosing. Conclusions: Our findings provide evidence to support the establishment of a novel mouse model of hypertriglyceridemia by oral administration of FSS oil (mainly increasing endogenous TG) and FSC oil (mainly elevating exogenous TG).

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).
Adenine ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; therapeutic use ; Double-Blind Method ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hepatitis B e Antigens ; immunology ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Male ; Medicine, Chinese Traditional ; Organophosphonates ; therapeutic use ; Young Adult

BACKGROUNDThe domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP) or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate.

METHODSThe study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment.

DISCUSSIONThe study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).

AIM:To explore efficacy of the different kinds of artificial tears treatment in patients with xerophthalmia after phacoemulsification combined with intraocular lens implantation.METHODS:Totally 280 patients (280 eyes) with xerophthalmia after operation in our hospital from January 2015 to June 2016 were selected.According to the different treatment methods, they were divided into control group (n=70;treated with tobramycin and dexamethasone eye ointment 3 times per day for 1wk, levofloxacin eye drops 3 times per day for 1wk, pranoprofen eye drops 4 times per day for 1mo), polyacrylic acid group (n=70;besides the treatment of control group, polyacrylic acid was used 4 times per for 1mo), polyethylene glycol group(n=70;besides the treatment of control group, polyethylene glycol was used 4 times per for 1mo) and sodium hyaluronate group (n=70;besides the treatment of control group, sodium hyaluronate was used 4 times per for 1mo).The tear film break up time (BUT), Schirmer Ⅰ test (SⅠt), symptoms of dry eye and corneal staining in four groups were observed.RESULTS:(1) BUT:The BUT of the four groups significantly increased after treatment(P<0.05);that of polyacrylic acid group, polyethylene glycol group, and sodium hyaluronate group was different compared with control group(P<0.05);the BUT in sodium hyaluronate group was significantly higher than the other groups after 2wk of treatment(P<0.05).(2) SⅠt:SⅠt of the four groups significant increased after treatment(P<0.05);that of polyacrylic acid group, polyethylene glycol group, and sodium hyaluronate group was different compared with control group(P<0.05);and the SⅠt in sodium hyaluronate group was significantly higher than other groups (P<0.05).(3) Xeroma score:the scores of dry eye significantly decreased after treatment in the four groups(P<0.05);that of polyacrylic acid group, polyethylene glycol group, and sodium hyaluronate group was different compared with control group(P<0.05);and the scores of the sodium hyaluronate group after 3wk was significantly lower compared with other groups(P<0.05).(4) Corneal staining score:the scores significantly decreased after treatment in the four groups(P<0.05);at 1 and 2wk after treatment the corneal staining score had not statistically different among the four groups (P>0.05);sodium hyaluronate group was significant lower than other groups in corneal staining score at 3wk and 1mo after treatment(P<0.05).CONCLUSION:Artificial tears in the treatment of xerophthalmia after cataract phacoemulsification combined with intraocular lens implantation has better clinical efficacy, which contains sodium hyaluronate may be the better than others.

OBJECTIVETo study the effect of perioperative immunomodulatory therapy on postoperative recurrence of rectal cancer.

METHODSThis prospective study was conducted among 238 rectal/anal cancer patients undergoing intersphincteric resection at our center between January, 2010 and January, 2011, among whom 150 were eligible to be included and completed the study. The 150 patients were randomized in a double-blinded fashion into 3 equal groups to receive immunomodulatory therapy with 8 mg/kg celecoxib (group A), 0.4 mg/kg Sou-Medrol (group B), or placebo (group C), given daily from 5 days before surgery to 5 days after surgery, and the postoperative cancer recurrence were compared.

RESULTSAt 3 days after the operation, the 3 groups showed significantly different C-reactive protein (CRP) levels, which decreased obviously in all the 3 groups compared with those at 1 day following the operation (P=0.022), especially in group B. The levels of interleukin-6 (IL-6) at 3 days after the operation also differed significantly between the 3 groups but were lower in all the 3 groups than those at 1 day after the operation (P=0.046), and this reduction was the most obvious in group A. COX-2 expression differed significantly between the 3 groups (P=0.017), among which group A showed the most obvious suppression of COX-2 expression. During the follow-up for a mean of 45 months, no significant difference in the recurrence rate was found between the 3 groups (P=0.549).

CONCLUSIONWith a lower efficacy than Sou-Medrol in decreasing postoperative inflammation, celecoxib produces a better effect in inhibiting COX-2 expression, but it does not lower postoperative recurrence rate of rectal cancer.

C-Reactive Protein ; metabolism ; Celecoxib ; Cyclooxygenase 2 Inhibitors ; therapeutic use ; Humans ; Immunomodulation ; Inflammation ; Interleukin-6 ; blood ; Neoplasm Recurrence, Local ; prevention & control ; Postoperative Period ; Prospective Studies ; Pyrazoles ; therapeutic use ; Rectal Neoplasms ; surgery ; therapy ; Sulfonamides ; therapeutic use

OBJECTIVETo detect changes of Foxp3 expression in the decidua in patients with preeclampsia and investigate the correlation of Foxp3-924 (rs2232365) polymorphisms with preeclampsia.

METHODSFrom October 2011 to December 2012, 252 normal pregnant women and 156 preeclampsia patients of Han nationality from the same geographic region were tested for Foxp3-924 genotypes by polymerase chain reaction with sequence-specific primer (PCR-SSP). Sixty-eight of the patients with preeclampsia (33 with mild and 35 with severe preeclampsia) and 30 of the normal pregnant women were also examined for Foxp3 expression in the decidua using immunohistochemical method.

RESULTSFoxp3 positive expression rates in the decidua was 51.52% in mild preeclampsia and 28.57% in severe preeclampsia cases, significantly lower than that in the control group (86.67%, P<0.05). In preeclampsia patients, the frequencies of Foxp3-924G/G, G/A, and A/A genotypes were 0.1346, 0.4615 and 0.4038, respectively, and the frequencies of Foxp3-924A and Foxp3-924 G were 0.6346 and 0.3654, respectively. The genotype frequencies of Foxp3-924G/G, G/A and A/A in the control group were 0.1508, 0.4087 and 0.4405, respectively, and the frequencies of Foxp3-924 A and Foxp3-924 G were 0.6448 and 0.3552, respectively. No significant differences were found in the gene frequencies of Foxp3-924G/A between preeclampsia patients and the control group (P>0.05).

CONCLUSIONThe expression level of Foxp3 in the placental tissue of preeclampsia patients is significantly lower than that in normal pregnant women, suggesting that lowered Foxp3 expression decreases the immunosuppressive function and causes imbalance of immune tolerance between maternal-fetal to induce preeclampsia. Foxp3-924 polymorphisms is not significantly correlated with the occurrence of preeclampsia.

Case-Control Studies ; Female ; Forkhead Transcription Factors ; genetics ; metabolism ; Gene Frequency ; Genotype ; Humans ; Placenta ; metabolism ; Polymorphism, Genetic ; Pre-Eclampsia ; genetics ; Pregnancy

To study the impact of the enterovirus 71(EV71) on the nuclear transport mechanism,The pGFP-NLS vector with nuclear location signal(NLS) was constructed, RD cells transfected by the pGFP-NLS vector were inoculated with the EV71 or cotransfected by EV71-2A vector. The results showed that GFP protein with NLS was expressed in the cytoplasm due to the inhibition of nuclear transport. In order to further study the mechanism of the EV71 to prevent nuclear transport,Nup62 was detected by Western blotting after RD cells were infected with EV71 or transfected by EV71-2A vector. The results showed that decreased expression of Nup62 could be detected after infection with EV71 and transfection by EV71-2A vector. This study demonstrates that the cleavage of Nup62 by EV71 2A protease may be the mechanism of nuclear transport inhibition.
Active Transport, Cell Nucleus ; Cell Line, Tumor ; Cell Nucleus ; metabolism ; Enterovirus A, Human ; enzymology ; genetics ; metabolism ; Enterovirus Infections ; virology ; Gene Expression Regulation, Viral ; Genetic Vectors ; Green Fluorescent Proteins ; metabolism ; Humans ; Membrane Glycoproteins ; metabolism ; Nuclear Localization Signals ; metabolism ; Nuclear Pore Complex Proteins ; metabolism ; Peptide Hydrolases ; metabolism ; Recombinant Fusion Proteins ; metabolism ; Transfection

BACKGROUNDGlutamic acid decarboxylase antibody (GADA) and protein tyrosine phosphatase antibody (IA-2A) are two major autoantibodies, which exert important roles in the process of type 1 diabetes mellitus (T1D). Our study aimed to investigate the changes in positivity and titers of GADA and IA-2A during the course of Chinese acute-onset T1D patients and their relationships with clinical features.

METHODSTwo hundreds and forty-seven Chinese newly diagnosed acute-onset T1D patients were consecutively recruited. GADA and IA-2A were detected at the time of diagnosis, one year later, 3-5 years later after diagnosis during the follow-up; all the clinical data were recorded and analyzed as well.

RESULTSDuring the course of acute-onset T1D, the majority of patients remained stable for GADA or IA-2A, however, a few patients changed from positivity to negativity and fewer patients converted from negativity to positivity. The prevalence of GADA was 56.3% at diagnosis, decreasing to 50.5% one year later, and 43.3% 3-5 years later while the corresponding prevalence of IA-2A were 32.8%, 31.0% and 23.3%, respectively. The median GADA titers were 0.0825 at diagnosis, declining to 0.0585 one year later and 0.0383 3-5 years later (P < 0.001), while the corresponding median titers were 0.0016, 0.0010, 0.0014 for IA-2A, respectively. Fasting C-peptide (FCP) and postprandial C-peptide 2 hours (PCP2h) levels of GADA or IA-2A negativity persistence patients were higher than those of positivity persistence and negativity conversion patients (P < 0.05) which indicated GADA or IA-2A negativity persistence T1D patients had a less loss of β cell function.

CONCLUSIONOur data suggest that repeated detection of GADA and IA-2A are necessary for differential diagnosis of autoimmune diabetes and the indirect prediction of the β cell function in Chinese patients.

Adolescent ; Adult ; Aged ; Antibodies ; therapeutic use ; Asian Continental Ancestry Group ; Child ; Child, Preschool ; Diabetes Mellitus, Type 1 ; drug therapy ; immunology ; Female ; Glutamate Decarboxylase ; immunology ; Glycated Hemoglobin A ; metabolism ; Humans ; Infant ; Male ; Middle Aged ; Protein Tyrosine Phosphatases ; immunology ; Young Adult