AIM: To investigate the differences in varying stages of non-proliferative diabetic retinopathy(NPDR)using optical coherence tomography angiography(OCTA).METHODS: Cross-sectional study. A total of 77 cases(77 eyes)of diabetic patients were included, and they were divided into non-diabetic retinopathy(NDR; 23 eyes)and non-proliferative diabetic retinopathy(NPDR; 54 eyes)groups, further subdivided into mild NPDR(20 eyes), moderate NPDR(20 eyes), and severe NPDR(14 eyes). Foveal avascular zone(FAZ)area, superficial and deep capillary plexus densities(SSP and DSP), and visual acuity(LogMAR)were compared between NDR and NPDR groups. Furthermore, the visual acuity, FAZ area and levels of SSP and DSP were compared in different degrees of NPDR. Correlation analysis were conducted to elucidate relationships between FAZ area, visual acuity, SSP, DSP, and severity of the disease.RESULTS: Compared with the NDR group, the visual acuity(LogMAR)and macular FAZ area increased, while SSP and DSP were decreased in the NPDR group(P<0.05); there were significant differences in visual acuity, FAZ area and SSP and DSP levels in different degrees of NPDR(P<0.05). Visual acuity(LogMAR)and FAZ area displayed a positive correlation with the severity of disease, while SSP and DSP showed a negative correlation.CONCLUSION: With the progression of NPDR, the visual acuity(LogMAR)and FAZ area increased, and the SSP and DSP decreased.

Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.

Objective To explore the correlations between serum Mas-related G protein-coupled receptor X2 (MRGPRX2), interleukin (IL)-4, IL-5, IL-6, IL-13, IL-23 and IL-33 levels and chronic spontaneous urticaria (CSU). Methods The clinical characteristics and laboratory data from 55 patients with CSU and 21 healthy controls at Huashan Hospital, Fudan University from February 2021 to September 2023 were collected. The disease activity and severity of CSU patients were assessed. Serum level of MRGPRX2 was tested using enzyme-linked immunosorbent assay (ELISA), and levels of IL-4, IL-5, IL-6, IL-13, IL-23, and IL-33 were measured using Luminex multiplex assay in all subjects. Spearman correlation analysis was used to evaluate the correlations between biomarkers and other parameters in CSU patients, and logistic regression analysis was performed to identify factors influencing CSU. Results CSU patients exhibited significantly higher serum levels of MRGPRX2 (2.41[0, 11.51] ng/mL vs 0[0, 2.86] ng/mL, P＝0.015) and IL-23 (0.09[0.04, 0.56] pg/mL vs 0.05[0.03, 0.08] pg/mL, P＝0.033) than healthy controls. There was no difference in levels of other cytokines between the two groups. There was no difference in levels of MRGPRX2 and cytokines between severe and non-severe CSU patients. Correlation analysis showed that serum MRGPRX2 levels in CSU patients were positively correlated with IL-4 (r＝0.345, P＝0.010) and IL-6 (r＝0.395, P＝0.003) levels. Logistic regression analysis indicated that MRGPRX2≥0.055 ng/mL and IL-23≥0.135 pg/mL were independent risk factors for CSU (P＜0.05). Conclusions Serum levels of MRGPRX2 and IL-23 in CSU patients are elevated, which may be involved in the pathogenesis of CSU.

OBJECTIVE To optimize β-cyclodextrin(β-CD)inclusion process of Cinnamomi Ramulus Formula Granules vola-tile constituents by orthogonal test,based on standard relation and information entropy method.METHODS On the basis of single factor experiments,the ratio of β-CD to aromatic aqueous solution,the inclusion temperature,and the inclusion time were selected as the investigating factors;the inclusion rate,drug loading,and standard relation of cinnamic aldehyde in inclusion complex were used as the evaluation index.The information entropy method was used to determine the weight coefficient of each index,then the comprehen-sive score was calculated,the inclusion process conditions were optimized by orthogonal experiment.The inclusion complex was charac-terized by thin layer chromatography,ultraviolet absorption spectroscopy,Fourier infrared spectroscopy,and X-ray diffraction.RE-SULTS The best inclusion process was that the ratio of β-CD to aromatic aqueous solution was 3∶100(g·mL-1),the inclusion temperature was 50℃,and the inclusion time was 1 h.The average inclusion rate of the obtained inclusion compound was 80.84%,the drug loading was 8.63%,and the standard relation was 0.91.The results of thin-layer chromatography,ultraviolet,infrared spec-troscopy and other characterization experiments showed that the volatile components in the aromatic aqueous solution successfully en-tered the β-CD cavity,and the inclusion complex was successfully prepared.CONCLUSION The optimum inclusion process is sta-ble and feasible,which can provide references for the preparation process of Cinnamomi Ramulus Formula Granules.

Gynecological cancer significantly affect the health of women.This review aimed to describe the global patterns and trends in the survival of patients with gynecological cancers.We searched PubMed,Embase,Web of Science,SinoMed,and SEER for survival analyses of cancer registration data of cervical,endometrial,and ovarian cancers published between 1980 and 2022.Globally,the highest 5-year observed survival rate for cervical cancer was 76.5%in Anshan,Liaoning,China(2008-2017).The 5-year observed survival rates of endometrial and ovarian cancers were higher in Finland(1995-1999,82.5%)and Singapore(1988-1992,62.0%).The 5-year relative survival rate of cervical cancer patients was higher in Haining,Zhejiang,China(2011-2014,85.8%).Korea ranked first at 89.0%and 64.5%for endometrial and ovarian cancers,respectively.Survival rates have improved for cervical,endometrial,and ovarian cancers.Patients aged≥75 years and those with advanced-stage disease had the worst 5-year survival rates.Survival rates were better for squamous cell carcinoma in cervical cancer,for endometrial carcinoma and mucinous adenocarcinoma in endometrial cancer,and for germ cell and sex-cord stromal tumors in ovarian cancer.Over the past four decades,the survival rates of gynecological cancers have increased globally,with notable increases in cervical and endometrial cancers.Survival rates are higher in developed countries,with a slow-growing trend.Future studies should focus on improving survival,especially in ovarian cancer patients.

Objective:To investigate the prognostic value of serum suppressor of cytokine signaling 3 (SOCS3) and thioredoxin-interacting protein (TXNIP) levels in transcatheter arterial chemoembolization (TACE) treatment of hepatocellular carcinoma (HCC) .Methods:A total of 107 HCC patients who underwent TACE treatment in Wuhan Hanyang Hospital from December 2019 to July 2021 were selected as the observation objects. According to the situation after TACE treatment, the patients were divided into poor prognosis group ( n=47) and good prognosis group ( n=60). Serum SOCS3 and TXNIP levels were detected by enzyme-linked immunosorbent assay, the prognostic factors were analyzed by logistic regression. The predictive value of serum SOCS3 and TXNIP levels before treatment for TACE treatment prognosis in patients with HCC was analyzed by receiver operator characteristic (ROC) curve. Results:There were no statistically significant differences between good prognosis group and poor prognosis group in age ( χ2=0.56, P=0.453), gender ( χ2=0.06, P=0.800), tumor size ( χ2=1.46, P=0.227), Child-Pugh grade ( χ2=0.26, P=0.608), tumor number ( χ2=0.77, P=0.382), cirrhosis ( χ2=0.03, P=0.860), TACE times ( χ2=0.16, P=0.691), alpha-fetoprotein level before treatment ( χ2=0.79, P=0.374), and hepatitis B surface antigen ( χ2=0.58, P=0.446). The proportion of TNM stage Ⅲ patients in the poor prognosis group (57.45%, 27/47) was higher than that in the good prognosis group (25.00%, 15/60), with a statistically significant difference ( χ2=11.64, P=0.001). The serum levels of SOCS3 and TXNIP in the good prognosis group before treatment were (114.34±20.39) and (45.64±6.41) pg/ml, respectively, while those in the poor prognosis group were (82.83±15.97) and (34.82±6.36) pg/ml, respectively, serum SOCS3 and TXNIP levels in the poor prognosis group were lower than those in the good prognosis group, with statistically significant differences ( t=8.71, P<0.001; t=8.70, P<0.001). After treatment, the serum SOCS3 and TXNIP levels in the good prognosis group were (139.65±24.32) and (64.75±7.58) pg/ml, respectively, while those in the poor prognosis group were (92.41±16.15) and (41.74±7.23) pg/ml, serum SOCS3 and TXNIP levels in the poor prognosis group were lower than those in the good prognosis group, with statistically significant differences ( t=11.48, P<0.001; t=15.90, P<0.001). Serum SOCS3 and TXNIP levels in both groups were significantly higher after treatment than before (all P<0.05). Multivariate analysis showed that TNM stage ( OR=2.53, 95% CI: 1.27-5.02, P=0.008) was an independent risk factor for prognosis in HCC patients after TACE treatment, SOCS3 ( OR=0.65, 95% CI: 0.44-0.96, P=0.031) and TXNIP ( OR=0.57, 95% CI: 0.36-0.89, P=0.014) were independent protective factors for prognosis in HCC patients after TACE treatment. ROC curve analysis showed that the sensitivity and specificity of the combined detection of serum SOCS3 and TXNIP before treatment in predicting prognosis of TACE treatment in HCC patients were 81% and 92%, respectively, the area under the curve was 0.92 (95% CI: 0.85-0.96) . Conclusion:The low levels of serum SOCS3 and TXNIP before TACE treatment in HCC patients may indicate poor prognosis after TACE treatment. The combined detection of the two has certain predictive value for judging the prognosis of HCC patients after TACE treatment.

Alcoholic liver disease (ALD) is a growing global health concern, and its early pathogenesis includes steatosis and steatohepatitis. Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD. Evidence shows that puerarin (Pue), an isoflavone isolated from Pueraria lobata, exerts cardio-protective, neuroprotective, anti-inflammatory, antioxidant activities. However, the therapeutic potential of Pue on ALD remains unknown. In the study, both the NIAAA model and ethanol (EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism. The results showed that Pue (100 mg·kg^-1) attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c, TNF-α, IL-6 and IL-1β, compared with silymarin (Sil, 100 mg·kg^-1). In vitro results were consistent within vivo results. Mechanistically, Pue might suppress liver lipid accumulation and inflammation by regulating MMP8. In conclusion, Pue might be a promising clinical candidate for ALD treatment.

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. In particular, increasing evidence has showed that astrocyte-mediated neuroinflammation is involved in the pathogenesis of PD. As a precious traditional Chinese medicine, bear bile powder (BBP) has a long history of use in clinical practice. It has numerous activities, such as clearing heat, calming the liver wind and anti-inflammation, and also exhibits good therapeutic effect on convulsive epilepsy. However, whether BBP can prevent the development of PD has not been elucidated. Hence, this study was designed to explore the effect and mechanism of BBP on suppressing astrocyte-mediated neuroinflammation in a mouse model of PD. PD-like behavior was induced in the mice by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg·kg^-1) for five days, followed by BBP (50, 100, and 200 mg·kg^-1) treatment daily for ten days. LPS stimulated rat C6 astrocytic cells were used as a cell model of neuroinflammation. THe results indicated that BBP treatment significantly ameliorated dyskinesia, increased the levels of tyrosine hydroxylase (TH) and inhibited astrocyte hyperactivation in the substantia nigra (SN) of PD mice. Furthermore, BBP decreased the protein levels of glial fibrillary acidic protein (GFAP), cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS), and up-regulated the protein levels of takeda G protein-coupled receptor 5 (TGR5) in the SN. Moreover, BBP significantly activated TGR5 in a dose-dependent manner, and decreased the protein levels of GFAP, iNOS and COX2, as well as the mRNA levels of GFAP, iNOS, COX2, interleukin (IL) -1β, IL-6 and tumor necrosis factor-α (TNF-α) in LPS-stimulated C6 cells. Notably, BBP suppressed the phosphorylation of protein kinase B (AKT), inhibitor of NF-κB (IκBα) and nuclear factor-κB (NF-κB) proteins in vivo and in vitro. We also observed that TGR5 inhibitor triamterene attenuated the anti-neuroinflammatory effect of BBP on LPS-stimulated C6 cells. Taken together, BBP alleviates the progression of PD mice by suppressing astrocyte-mediated inflammation via TGR5.
Humans ; Mice ; Rats ; Animals ; Aged ; Middle Aged ; Parkinson Disease/pathology* ; Astrocytes/pathology* ; Powders/therapeutic use* ; Ursidae/metabolism* ; NF-kappa B/metabolism* ; Neuroinflammatory Diseases ; Neurodegenerative Diseases/metabolism* ; Cyclooxygenase 2/metabolism* ; Lipopolysaccharides/pharmacology* ; Bile ; Mice, Inbred C57BL ; Microglia ; Disease Models, Animal

Objective:To compare anatomical locking plate fixation with versus without reconstruction of the coracoclavicular ligament in the treatment of acute and old Neer Ⅱb unstable distal clavicle fractures.Methods:From January 2015 to November 2020, 80 Neer Ⅱb distal clavicle fractures were treated at Department of Orthopaedics, The First Hospital Affiliated to China Pharmaceutical University. There were 49 males and 31 females, aged from 32 to 78 years (average, 47.8 years). Of the 50 fresh fractures, 25 were treated by internal fixation with anatomical locking plate of distal clavicle plus reconstruction of the coracoclavicular ligament with suture anchor (reconstruction group A) while the other 25 by only internal fixation with anatomical locking plate of distal clavicle (non-reconstruction group A). Of the 30 old fractures which had not got united over 3 weeks after injury, 15 were treated by internal fixation with anatomical locking plate of distal clavicle plus reconstruction of the coracoclavicular ligament with suture anchor (reconstruction group B) while the other 15 by only internal fixation with anatomical locking plate of distal clavicle (non-reconstruction group B). At 1, 3 and 6 months postoperatively, Constant-Murley scale and visual analogue scale (VAS) were used to evaluate shoulder function and pain. X-ray follow-ups were conducted to measure the coracoclavicular distance and observe fracture union and complications at the last follow-up.Results:All the 80 patients were followed up for 6 to 24 months (average, 13.8 months). For reconstruction group A and non-reconstruction group A, respectively, the union time for fresh fractures was (11.7±2.8) weeks versus (13.4±1.3) weeks, the rate of coracoclavicular distance increase 12.7%±6.2% versus 14.2%±8.0%, the Constant-Murley score 92.2±4.4 versus 90.9±5.7, showing no statistically significant difference between the 2 groups (all P>0.05). For reconstruction group B and non-reconstruction group B, respectively, the union time for old fractures was (12.8±1.9) weeks versus (19.4±6.7) weeks, the rate of coracoclavicular distance increase 12.3%±6.7% versus 21.5%±13.1%, the Constant-Murley score 93.0±5.9 versus 83.5±8.5, showing statistically significant differences between the 2 groups (all P<0.05). Conclusions:For fresh Neer Ⅱb distal clavicle fractures, simple anatomical locking plate fixation can achieve satisfactory curative efficacy without additional reconstruction of the coracoclavicular ligament. However, for old Neer IIb distal clavicle fractures, additional reconstruction of the coracoclavicular ligament can better maintain the stability of the acromioclavicular joint, reduce the risk of internal fixation failure, and achieve better outcomes.