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 evaluate the effectiveness and safety of transcutaneous electrical acupoint stimulation (TEAS) for improving postoperative cognitive function in senior patients undergoing video-assisted thoracoscopic surgical (VATS). METHODS: From January to December 2020, 97 participants were randomly assigned to the TEAS group (49 cases) and the control group (48 cases) by a random number table. The patients in the TEAS group received TEAS, at the bilateral Neiguan (PC 6) and Zusanli (ST 36) acupoints. The control group received sham TEAS. The stimulation was started from 30 min before surgery until the end of the operation. The primary outcome was the incidence of pstoperative cognitive dysfunction (POCD), diagnosed based on the changes in the Mini-Mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. The secondary outcomes were plasma levels of S100β protein and neuron-specific enolase (NSE). RESULTS: The incidence of POCD on day 1 and 3 after surgery in the TEAS group was significantly lower than that in the control group [day 1 after surgery: 28.3% (13/46) vs. 52.3% (23/44), P=0.028; day 3 after surgery: 21.7% (10/46) vs. 40.9% (18/44), P=0.043]. Compared with baseline, the MMSE and MoCA scores decreased to various extents in both groups. The MMSE scores on day 1, 3, and 5 after surgery and MoCA scores on day 1, 3, 5, and 7 after surgery in the TEAS group were higher than those in the control group (all P<0.05) in both groups. Compared with baseline, the plasma levels of S100β and NSE were significantly increased at 4, 8, 12, 24 h after surgery (all P<0.05). Compared with the control group, the plasma levels of S100β and NSE were lower in the TEAS group at 4, 8, 12, and 24 h after surgery (all P<0.05). No obvious adverse events were found during the trial. CONCLUSION Application of TEAS in senior patients after VATS could reduce incidence of POCD and improve postoperative cognitive function.
Acupuncture Points ; Cognition ; Humans ; Postoperative Period ; Thoracic Surgery, Video-Assisted/adverse effects* ; Transcutaneous Electric Nerve Stimulation

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 the clinical manifestations, treatments, and prognosis of pediatric patients with Talaromyces marneffei infection. Methods: In this retrospective study, 7 children diagnosed with Talaromyces marneffei infection in Shenzhen Children's Hospital from July 2017 to October 2021 were recruited. The clinical features, radiology, pathogen detection, immunological evaluation, treatments, and prognosis were analyzed. Results: In 7 cases, 5 were male, 2 were females. The age was from 0.75 to 8.75 years. The main clinical manifestations were fever in 7 cases, cough in 6 cases, malnutrition in 4 cases, papules in 2 cases and medical history of recurrent infection in 3 cases. Physical examination showed that all 7 patients had hepatosplenomegaly, 4 had superficial lymphadenopathy. Laboratory examination showed that 6 cases had decreased hemoglobin and 3 cases had decreased platelet. Chest CT showed that 4 cases had patchy shadows, pleural effusion, mediastinal or axillary lymph node enlargement, 3 had nodular shadows and 2 had cavities. The positive ratio of Talaromyces marneffei culture was 2/2 with tissue samples, 4/5 with bone marrow. The positive ratio was 3/4 by metagenomic next generation sequencing. The fungus was detected in 3 cases by smear microscopy of bone marrow and (or) peripheral blood. All patients were negative for human immunodeficiency virus by the immune function assay. However, 5 cases were confirmed as primary immunodeficiency disease, including 2 cases with high IgM syndrome, 2 with STAT1 gene variation, and the last with severe combined immunodeficiency (IL2RG gene variation). Exclude 1 case which gave up treatment due to acute intracranial infection, and the other patients received effective treatments along with amphotericin B, voriconazole, and itraconazole alone or in combination. Two cases relapsed after medication withdrawal, but 1 case got complete rehabilitation after hematopoietic stem cell transplantation. Conclusions: The clinical manifestations involve multisystem, the common charateristics are fever and cough. The chest CT imaging manifestations are diverse, it should be considered in differentiating tuberculosis. The amphotericin B, voriconazole and itraconazole are effective, but it will easily relapse when withdrawing those antifungal agents.
Amphotericin B/therapeutic use* ; Antifungal Agents/therapeutic use* ; Child ; Child, Preschool ; Cough ; Female ; Fever ; Humans ; Infant ; Itraconazole/therapeutic use* ; Male ; Mycoses ; Retrospective Studies ; Talaromyces ; Voriconazole

This study investigated the correlation between periprostatic fat thickness (PPFT) measured on magnetic resonance imaging and lower urinary tract symptoms, erectile function, and benign prostatic hyperplasia (BPH) progression. A total of 286 treatment-naive men diagnosed with BPH in our department between March 2017 and February 2019 were included. Patients were divided into two groups according to the median value of PPFT: high (PPFT >4.35 mm) PPFT group and low (PPFT <4.35 mm) PPFT group. After the initial evaluation, all patients received a combination drug treatment of tamsulosin and finasteride for 12 months. Of the 286 enrolled patients, 244 completed the drug treatment course. Patients with high PPFT had larger prostate volume (PV; P = 0.013), higher International Prostate Symptom Score (IPSS; P = 0.008), and lower five-item version of the International Index of Erectile Function (IIEF-5) score (P = 0.002) than those with low PPFT. Both high and low PPFT groups showed significant improvements in PV, maximum flow rate, IPSS, and quality of life score and a decrease of IIEF-5 score after the combination drug treatment. The decrease of IIEF-5 score was more obvious in the high PPFT group than that in the low PPFT group. In addition, more patients in the high PPFT group underwent prostate surgery than those in the low PPFT group. Moreover, Pearson's correlation coefficient analysis indicated that PPFT was positively correlated with age, PV, and IPSS and negatively correlated with IIEF-5 score; however, body mass index was only negatively correlated with IIEF-5 score.

Objective: To compare the effects of 3 treatment strategies (emergent surgery, self-expanding metallic stents, self-expanding metallic stents plus neoadjuvant chemotherapy) on postoperative anal function and quality of life in patients with complete obstructive left hemicolon cancer. Methods: A retrospective cohort study was conducted. Clinical data of patients with complete obstructive left hemicolon cancer admitted to General Surgery Department of Beijing Chaoyang Hospital between January 2017 and October 2019 were retrospectively collected. Patient inclusion criteria: (1) complete obstructive left hemicolon cancer was confirmed through clinical manifestation and abdominal computed tomography; (2) adenocarcinoma was confirmed by postoperative pathology; (3) emergent radical resection of primary tumor was performed with temporary stoma, or radical resection of primary tumor and primary anastomosis was performed without stoma, 7 to 14 days after completion of insertion of self-expanding metallic stents. Patients who did not receive stoma reversion after emergent operation were excluded. According to different therapies, patients were divided into three groups: emergent surgery (ES) group, self-expanding metallic stents (SEMS) group and self-expanding metallic stents plus neoadjuvant chemotherapy (SEMS+NAC) group. Wexner score for incotinence (higher score indicates the worse anal function), Vaizey score (>10 indicates fecal incontinence) and low anterior resection syndrome (LARS) scale (higher score indicates the worse anal function) were applied to evaluate anal function of patients among groups at postoperative 1-, 6- and 12-month. EORTC QLQ-C30 questionnaire was used to assess the quality of life. Risk factors of decreased anal function were identified by logistic regression analysis. Results: A total of 72 patients were enrolled, including 27 (37.5%) patients in ES group, 23 (31.9%) in SEMS group and 22 (30.6%) in SEME+NAC group. The baseline characteristics including age, gender, tumor location, comorbidities, total blood loss, operation time and postoperative complications, were comparable among groups, except that the proportion of laparoscopic surgery was significantly lower in ES group (4/27, 14.9%) than that in SEMS (15/23, 65.2%) and SEMS+NAC group (16/22, 72.7%) with significant difference (P<0.001). The follow-up ended up to October 2020, and the overall follow-up rate was 79.2% (57/72). No significant differences existed in the Wexner score of patients among groups at postoperative 1-, 6- and 12-month (all P>0.05). The Vaizey scores at postoperative 1-month in ES, SEMS and SEMS+NAC group were 7 (0-17), 3 (0-7) and 4 (0-8) respectively with significant difference (H=18.415, P=0.001), and the scores in SEMS and SEMS+NAC groups were significantly lower than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC group (P>0.05). Vaizey scores at postoperative 6- and 12-month among 3 groups were not significantly different (both P>0.05). The LARS scores at postoperative 1-month in ES, SEMS and SEMS+NAC groups were 20 (0-37), 15 (0-24) and 16 (0-28) respectively with significant difference (H=3.660, P=0.036), and the scores in SEMS and SEMS+NAC groups were significantly lower than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC groups (P>0.05). LARS scores at postoperative 6- and 12-month among 3 groups were not significantly different (both P>0.05). The QLQ-C30 score revealed that the social function of patients in SEMS group and SEMS+NAC group was significantly better than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC group (P>0.05). The logistic regression analysis revealed that only ES was an independent risk factor of decreased anal function (OR=2.264, 95% CI: 1.098-4.667, P=0.027). Conclusion: Compared to ES, SEMS may improve quality of life and short-term anal function of patients with complete obstructive left hemicolon cancer.
Humans ; Intestinal Obstruction ; Postoperative Complications ; Quality of Life ; Rectal Neoplasms ; Retrospective Studies ; Syndrome ; Treatment Outcome

Objective: To observe the therapeutic effect of mild moxibustion on irritable bowel syndrome (IBS) visceral hyperalgesiamodel rats and its regulatory effect on P2X3 receptors in the spinal cord, anterior cingutate cortex (ACC) and thalamic ventral posterolateral nucleus (VPL). Methods: Thirty 8-day-old newborn rats were randomly divided into a normal group (n=6) and a modeling group (n=24) according to the completely random number table method. Rats in the normal group were bred routinely, and those in the modeling group were subjected to preparing IBS chronic visceral hyperalgesia model using colorectal distention (CRD) in stimulation method. Rats successfully modelled were re-divided into a model group, a mild moxibustion group, a P2X3 receptor antagonist group, and a normal saline group according to the completely random number table method with 6 rats in each group. Rats in each group received corresponding interventions from the 37-day old, once a day for 7 consecutive days. Immunohistochemistry and Western blot assays were used to detect P2X3 protein expressions in the spinal cord, ACC and VPL of rats. Results: Under different intensities of CRD stimulation, the abdominal withdrawal reflex (AWR) scores of the model group were significantly increased versus the normal group (all P<0.05); the AWR scores of the mild moxibustion group and the P2X3 receptor antagonist group were significantly reduced versus the model group (all P<0.01). The P2X3 protein expressions in rat spinal cord, ACC and VPL tissues of the model group were significantly increased versus the normal group (all P<0.01); the P2X3 protein expressions in rat spinal cord, ACC and VPL tissues of the mild moxibustion group and the P2X3 receptor antagonist group were significantly reduced versus the model group (all P<0.01). Conclusion: Mild moxibustion can inhibit the P2X3 receptor expressions in the spinal cord, ACC, and VPL tissues of IBS visceral hyperalgesia model rats, which may be the mechanism of mild moxibustion in relieving the central sensitization of rats with IBS visceral hyperalgesia.

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

Catalpol is the main active ingredient of an extract from Radix rehmanniae, which in a previous study showed a protective effect against various types of tissue injury. However, a protective effect of catalpol on uterine inflammation has not been reported. In this study, to investigate the protective mechanism of catalpol on lipopolysaccharide (LPS)-induced bovine endometrial epithelial cells (bEECs) and mouse endometritis, in vitro and in vivo inflammation models were established. The Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway and its downstream inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), western blot (WB), and immunofluorescence techniques. The results from ELISA and qRT-PCR showed that catalpol dose-dependently reduced the expression of pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6, and chemokines such as C-X-C motif chemokine ligand 8 (CXCL8) and CXCL5, both in bEECs and in uterine tissue. From the experimental results of WB, qRT-PCR, and immunofluorescence, the expression of TLR4 and the phosphorylation of NF-κB p65 were markedly inhibited by catalpol compared with the LPS group. The inflammatory damage to the mouse uterus caused by LPS was greatly reduced and was accompanied by a decline in myeloperoxidase (MPO) activity. The results of this study suggest that catalpol can exert an anti-inflammatory impact on LPS-induced bEECs and mouse endometritis by inhibiting inflammation and activation of the TLR4/NF-κB signaling pathway.
Animals ; Cattle ; Chemokines/genetics* ; Cytokines/genetics* ; Endometritis/drug therapy* ; Epithelial Cells/drug effects* ; Female ; Inflammation/prevention & control* ; Iridoid Glucosides/therapeutic use* ; Lipopolysaccharides/pharmacology* ; Mice ; NF-kappa B/physiology* ; Signal Transduction/drug effects* ; Toll-Like Receptor 4/physiology*

OBJECTIVE: To investigate the effects of the Arg-Gly-Asp polypeptedes (RGD) peptides-modified porous tantalum surface on osteoblasts morphology and expressions of osteogenesis factors, and to evaluate RGD peptides promotes junctura ossium of tantalum-bone interface in vivo. METHODS: RGD peptides of different concentrations (1 g/L, 5 g/L, and 10 g/L) were loaded to porous tantalum slices with a diameter of 10 mm and a thickness of 3 mm by physical absorption. The 3rd generation of MG63 cells were co-cultured with tantalum and divided into 4 groups: Ta-cells (control) group, 1 g/L cells/Ta/RGD group, 5 g/L cells/Ta/RGD group, and 10 g/L cells/Ta/RGD group. Porous tantalum compo-sites and osteoblasts-tantalum interface were observed by scanning electron microscopy. The adhesion rate of osteoblasts was detected and immunocytochemistry was used to detect the expressions of filamentous actin (F-actin), osteocalcin (OC) and fibronectin (FN). RESULTS: The scanning electron microscope (SEM) revealed that osteoblasts distributed on the surface of porous tantalum and secreted extracellular matrix on outside and inner of micro-pores. The osteoblasts adhesion rate on porous tantalum modified with RGD was higher than that in the unmodified porous tantalum at the end of 24, 48, and 72 hours. The best adhesion effect was got in 5 g/L cells/Ta/RGD group at hour 48 [(68.07±3.80) vs. (23.40±4.39), P<0.05]. The results of immunocytochemistry showed that the expressions intensity of F-actin, OC and FN in osteoblasts on porous tantalum modified groups with RGD were stronger than that in the unmodified groups, and the expressions of 5 g/L cells/Ta/RGD group were significantly higher than those in the 10 g/L group and 1 g/L group [OC: (18.08±0.08) vs. (15.14±0.19), P<0.05; (18.08±0.08) vs. (14.04±0.61), P<0.05. FN: (24.60±0.98) vs. (15.90±0.53), P<0.05; (24.60±0.98) vs. (15.30±0.42), P<0.05. F-actin: (29.20±1.31) vs. (24.50±1.51), P<0.05; (29.20±1.31) vs. (16.92±0.40), P<0.05]. Correspondingly F-actin in osteoblasts was showed in longitudinal arrangement, and the expressions intensity was stronger than those OC and FN. CONCLUSION The RGD peptides is beneficial to enhance adhesion of osteoblast, spreading and reorganization of cytoskeleton on porous tantalum surface and improve the interface morphology, further promoting osteoblasts-tantalum conjunctive interface osseointegration.
Cell Adhesion ; Oligopeptides ; Osteoblasts/physiology* ; Osteogenesis ; Tantalum