AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR), and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA screening indicators to detect concurrent DR at an early stage.METHODS: A total of 200 patients who treated in the ophthalmology department of the Seventh Affiliated Hospital, Sun Yat-sen University from 2022 to 2023 were included, including 95 first-diagnosed DR patients and 105 patients without DR, and all patients underwent OCTA examination and a collection of demographics and renal function parameters. After a quality check, automated measurements of the foveal avascular zone area, vessel density(VD), and perfusion density(PD)of both 3 mm×3 mm and 6 mm×6 mm windows were obtained.RESULTS: Using random forest and multivariate Logistic regression methods, we developed a diagnostic model for DR based on 12 variables(age, FBG, SBP, DBP, HbA1c, ALT, ALP, urea/Scr, DM duration, HUA, DN, and CMT). Adding specific OCTA parameters enhanced the efficacy of the existing diagnostic model for DR(outer vessel density in 6 mm×6 mm window, AUC=0.837 vs 0.819, P=0.03). In the study of DN patients, the parameters in the 6 mm×6 mm window improved the diagnostic efficacy of DR(inner VD; outer VD; full VD; outer PD; full PD).CONCLUSION:The outer VD in the 6 mm×6 mm window can enhance the efficacy of the traditional DR diagnostic model. Meanwhile, compared with the 3 mm×3 mm window, the microvascular parameters in the 6 mm× 6 mm window focusing on DN patients can be more sensitive to diagnosing the occurrence of DR.

OBJECTIVE: To investigate the biomechanical characteristics of Schatzker type Ⅱ tibial plateau fracture fixed by different bone grafting methods and internal fixations. METHODS: Twenty-four embalmed specimens of adult knee joint were selected to make Schatzker type Ⅱ tibial plateau fracture models, which were randomly divided into 8 groups (groups A1-D1 and groups A2-D2, n=3). After all the fracture models were restored, non-structural iliac crest bone grafts were implanted in group A1-D1, and structural iliac crest bone grafts in groups A2-D2. Following bone grafting, group A was fixed with a lateral golf locking plate, group B was fixed with lateral golf locking plate combined compression bolt, group C was fixed with lateral tibial "L"-shaped locking plate, and group D was fixed with lateral tibial "L"-shaped locking plate combined compression bolt. Compression and cyclic loading tests were performed on a biomechanical testing machine. A distal femur specimen or a 4-cm-diameter homemade bone cement ball were used as a pressure application mould for each group of models. The specimens were loaded with local compression at a rate of 10 N/s and the mechanical loads were recorded when the vertical displacement of the split bone block reached 2 mm. Then, compressive and cyclic loading tests were conducted on the fixed models of each group. The specimens were compression loaded to 100, 400, 700, and 1 000 N at a speed of 10 N/s to record the vertical displacement of the split bone block. The specimens were also subjected to cyclic loading at 5 Hz and 10 N/s within the ranges 100-300, 100-500, 100-700, and 100-1 000 N to record the vertical displacement of the split bone block at the end of the entire cyclic loading test. The specimens were subjected to cyclic loading tests and the vertical displacement of the split bone block was recorded at the end of the test. RESULTS: When the vertical displacement of the collapsed bone block reached 2 mm, the mechanical load of groups A2-D2 was significantly greater than that of groups A1-D1 ( P<0.05). The mechanical load of groups B and D was significantly greater than that of group A under the two bone grafting methods ( P<0.05); the local mechanical load of group D was significantly greater than that of groups B and C under the structural iliac crest bone grafts ( P<0.05). There was no significant difference ( P>0.05) in the vertical displacement of the split bone blocks between the two bone graft methods when the compressive load was 100, 400, 700 N and the cyclic load was 100-300, 100-500, 100-700 N in groups A-D. However, the vertical displacement of bone block in groups A1-D1 was significantly greater than that in groups A2-D2 ( P<0.05) when the compressive loading was 1 000 N and the cyclic load was 100-1 000 N. The vertical displacement of bone block in group B was significantly smaller than that in group A, and that in group D was significantly smaller than that in group C under the same way of bone graft ( P<0.05). CONCLUSION Compared with non-structural iliac crest bone grafts implantation, structural iliac crest bone grafts is more effective in preventing secondary collapse of Schatzker type Ⅱ tibial plateau fracture, and locking plate combined with compression bolt fixation can provide better articular surface support and resistance to axial compression, and the lateral tibial "L"-shaped locking plate can better highlight its advantages of "raft" fixation and show better mechanical stability.
Humans ; Bone Transplantation/methods* ; Tibial Fractures/physiopathology* ; Fracture Fixation, Internal/instrumentation* ; Biomechanical Phenomena ; Bone Plates ; Ilium/transplantation* ; Adult ; Tibia/surgery* ; Bone Cements ; Knee Joint/surgery* ; Male ; Tibial Plateau Fractures

Although cancer immunotherapy has made great strides in the clinic, it is still hindered by the tumor immunosuppressive microenvironment (TIME). The stimulator of interferon genes (STING) pathway which can modulate TIME effectively has emerged as a promising therapeutic recently. However, the delivery of most STING agonists, specifically cyclic dinucleotides (CDNs), is performed intratumorally due to their insufficient pharmacological properties, such as weak permeability across cell membranes and vulnerability to nuclease degradation. To expand the clinical applicability of CDNs, a novel pH-sensitive polycationic polymer-modified lipid nanoparticle (LNP-B) system was developed for intravenous delivery of CDNs. LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor, spleen, and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages. These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models. In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.

OBJECTIVES: To explore the active components that mediate the therapeutic effect of Centella asiatica on psoriasis and their therapeutic mechanisms. METHODS: TCMSP, TCMIP, PharmMapper, Swiss Target Prediction, GeneCards, OMIM and TTD databases were searched for the compounds in Centella asiatica and their targets and the disease targets of psoriasis. A drug-active component-target network and the protein-protein interaction network were constructed, and DAVID database was used for pathway enrichment analysis. In a RAW264.7 macrophage model of LPS-induced inflammation, the anti-inflammatory effect of 7.5, 15, 30, and 60 μmol/L quercetin, asiaticoside, and asiatic acid, which were identified as the main active components in Centella asiatica, were tested by measuring cellular production of NO, TNF‑α and IL-6 using Griess method and ELISA and by detecting mRNA expressions of IL-23, IL-17A, TNF-α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727) with RT-qPCR and Western blotting. RESULTS: A total of 139 targets of Centella asiatica and 4604 targets of psoriasis were obtained, and among them CASP3, EGFR, PTGS2, and ESR1 were identified as the core targets. KEGG analysis suggested that quercetin, asiaticoside, and asiatic acid in Centella asiatica were involved in cancer and IL-17 and MAPK signaling pathways. In the RAW264.7 macrophage model of inflammation, treatment with quercetin significantly reduced cellular production of NO, TNF‑α and IL-6, and lowered mRNA expressions of IL-23, IL-17A, TNF‑α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727). CONCLUSIONS Quercetin, asiaticoside and asiatic acid are the main active components in Centella asiatica to mediate the therapeutic effect against psoriasis, and quercetin in particular is capable of suppressing cellular production of NO, TNF‑α and IL-6 and regulating the IL-23/IL-17A inflammatory axis by mediating STAT3 phosphorylation to inhibit inflammatory response.
Quercetin/pharmacology* ; Psoriasis/metabolism* ; STAT3 Transcription Factor/metabolism* ; Mice ; Animals ; Centella/chemistry* ; Triterpenes/pharmacology* ; Phosphorylation ; Interleukin-17/metabolism* ; Interleukin-23/metabolism* ; RAW 264.7 Cells ; Pentacyclic Triterpenes/pharmacology* ; Macrophages/drug effects* ; Signal Transduction ; Plant Extracts

ObjectiveTo explore the influencing factors of occupational hand-arm vibration disease (OHAVD) caused by handheld workpiece polishing. Methods A total of 222 OHAVD patients (case group), 275 hand-transmitted vibration-exposed workers (exposed group) and 243 healthy workers without hand-transmitted vibration exposure (control group) in a sports equipment manufacturing enterprise were selected as the study subjects using the convenience sampling method. Worksite survey of occupational health was conducted on these three groups, and the human vibration measurement equipment was used to measure the vibration exposure level of handheld vibration among the study subjects. The 8-hour energy equivalent frequency-weighted vibrating acceleration ［A(8)］ and cumulative vibration exposure level (CVEL) were calculated. Results The prevalence of coldness, numbness, tingling fingers, and vibration-induced white finger was higher in the exposed group and the case group compared with the control group (all P<0.05). The prevalence of the above-mentioned hand symptoms was higher in the case group compared with the exposed group (all P<0.05). The A(8) and CVEL levels of the study subjects in the case group were higher than those in the exposed group (all P<0.05). Binary logistic analysis result showed that age and CVEL were both influencing factors of OHAVD (all P<0.05). According to the restricted cubic spline models, CVEL of the study subjects in the exposed group had a positive nonlinear dose-response relationship with the risk of OHAVD (overall trend P<0.01, nonlinear P<0.01), indicating an increasing risk of OHAVD with increasing CVEL. Conclusion Hand-transmitted vibration exposure is a risk factor for OHAVD. Early intervention should be carried out for hand-transmitted vibration-exposed individuals to reduce vibration-exposed levels and control vibration exposure time.

Objective: As an indolent malignant tumor, the long-term management of low-grade endometrial stromal sarcoma (LGESS) patients required awareness, especially the management of recurrences. Unfortunately, few studies focused on the treatment of recurrent LGESS. Our study aimed to investigate the prognostic factors and the value of recurrent surgery on recurrent LGESS. Methods: This retrospective study consecutively recruited patients with pathologically diagnosed recurrent LGESS at our center from April 1, 2004 to April 1, 2020. Results: After a median follow-up of 137.0 months (95% confidence interval=85.4–188.6), the 5-year cumulative survival rate of the cohort of 38 patients with recurrent LGESS was 71.1%. The median overall survival (OS) and post-recurrence survival (PRS) was 156 and 89.0 months. Survival analysis showed that patients with younger age, positive estrogen receptor (ER) and optimal abdominopelvic debulking in the first recurrent surgery had better prognosis (p<0.05). Multivariate analysis showed that optimal abdominopelvic debulking in the first recurrent surgery was the only independent prognostic factor for OS and PRS (OS=216.0/35.0 months, hazard ratio [HR]=5.319, p=0.034; PRS=not reached/4.0 months, HR=10.900, p=0.006). There was no significant difference in OS and PRS between patients recurred only once and those recurred at least twice (p>0.05). Conclusions The prognosis of recurrent LGESS was favorable. Optimal debulking of no residual tumor in abdominal and pelvic cavity should be the first choice of treatment for recurrent patients, while preservation of ovary or fertility should not be recommended.

Objective: As an indolent malignant tumor, the long-term management of low-grade endometrial stromal sarcoma (LGESS) patients required awareness, especially the management of recurrences. Unfortunately, few studies focused on the treatment of recurrent LGESS. Our study aimed to investigate the prognostic factors and the value of recurrent surgery on recurrent LGESS. Methods: This retrospective study consecutively recruited patients with pathologically diagnosed recurrent LGESS at our center from April 1, 2004 to April 1, 2020. Results: After a median follow-up of 137.0 months (95% confidence interval=85.4–188.6), the 5-year cumulative survival rate of the cohort of 38 patients with recurrent LGESS was 71.1%. The median overall survival (OS) and post-recurrence survival (PRS) was 156 and 89.0 months. Survival analysis showed that patients with younger age, positive estrogen receptor (ER) and optimal abdominopelvic debulking in the first recurrent surgery had better prognosis (p<0.05). Multivariate analysis showed that optimal abdominopelvic debulking in the first recurrent surgery was the only independent prognostic factor for OS and PRS (OS=216.0/35.0 months, hazard ratio [HR]=5.319, p=0.034; PRS=not reached/4.0 months, HR=10.900, p=0.006). There was no significant difference in OS and PRS between patients recurred only once and those recurred at least twice (p>0.05). Conclusions The prognosis of recurrent LGESS was favorable. Optimal debulking of no residual tumor in abdominal and pelvic cavity should be the first choice of treatment for recurrent patients, while preservation of ovary or fertility should not be recommended.

Objective: As an indolent malignant tumor, the long-term management of low-grade endometrial stromal sarcoma (LGESS) patients required awareness, especially the management of recurrences. Unfortunately, few studies focused on the treatment of recurrent LGESS. Our study aimed to investigate the prognostic factors and the value of recurrent surgery on recurrent LGESS. Methods: This retrospective study consecutively recruited patients with pathologically diagnosed recurrent LGESS at our center from April 1, 2004 to April 1, 2020. Results: After a median follow-up of 137.0 months (95% confidence interval=85.4–188.6), the 5-year cumulative survival rate of the cohort of 38 patients with recurrent LGESS was 71.1%. The median overall survival (OS) and post-recurrence survival (PRS) was 156 and 89.0 months. Survival analysis showed that patients with younger age, positive estrogen receptor (ER) and optimal abdominopelvic debulking in the first recurrent surgery had better prognosis (p<0.05). Multivariate analysis showed that optimal abdominopelvic debulking in the first recurrent surgery was the only independent prognostic factor for OS and PRS (OS=216.0/35.0 months, hazard ratio [HR]=5.319, p=0.034; PRS=not reached/4.0 months, HR=10.900, p=0.006). There was no significant difference in OS and PRS between patients recurred only once and those recurred at least twice (p>0.05). Conclusions The prognosis of recurrent LGESS was favorable. Optimal debulking of no residual tumor in abdominal and pelvic cavity should be the first choice of treatment for recurrent patients, while preservation of ovary or fertility should not be recommended.

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC₅₀ = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

Objective:To compare the differences in important parameters between the articulation assessment and training system of intelligently extracted speech with those from the Praat acoustic software and those manually extracted.Methods:The speech of thirty-two normal subjects was captured using the intelligent articulation assessment and training system and using Praat acoustic software. The former analyzed the mean fundamental frequencies (mF0s), the first formant peaks (F1s) and the second formant peak (F2s) of the sustained vowels /a/, /i/ and /u/. The speech parameters collected by the traditional Praat software were extracted and analyzed by professionals. The two tools′ consistency in terms of these important acoustic parameters was analyzed.Results:The results with all 32 subjects when retested returned ICC values above 0.9 with all three vowels with the exception of mF0 for /u/ (ICC=0.75), indicating excellent retest reliability for the articulation assessment and training system. The ICC values also indicated excellent consistency between the two kinds of software in analyzing mF0, F1 and F2 of the three vowels. The mF0, F1, F2, FCR, VAI, tongue spacing, VSA, and mandibular spacing of all three vowels were mostly distributed within the 95% confidence interval of the data points in Bland-Altman plots, indicating the high accuracy of both acoustic analysis systems in speech measurement. The mean fundamental frequency values of the male long vowels /a/, /i/ and /u/ were all significantly lower than for the female long versions.Conclusions:The retest reliability of the articulation assessment and training system was good, and the results of the articulation check in the natural state were in good consistency compared to the Praat check and were interchangeable in the articulation check.