ObjectiveTo evaluate the efficacy and possible mechanism of Wei's Huoxue Tongluo Formula （韦氏活血通络方，WHTF） in treating atrophic-stage non-arteritic anterior ischemic optic neuropathy （NAION） with qi deficiency and blood stasis. MethodsA total of 82 atrophic-stage NAION patients with qi deficiency and blood stasis were randomly divided into a treatment group and a control group， with 41 cases in each group. The treatment group was given oral administration of WHTF twice a day plus acupoint injection of distilled water 2 ml at Taiyang （EX-HN5） once daily， while the control group received injection of compound anisodine injection 2 ml at Taiyang （EX-HN5） once daily and oral administration of WHTF placebo twice a day. Both groups received treatment for a course of 14 days. The best-corrected visual acuity （BCVA）， optic disc perfusion density （PD）， flux index （FI）， macular superficial PD， vascular density （VD）， and traditional Chinese medicine （TCM） syndrome scores were compared between groups before treatment and on day 7 and day 14 of treatment. Additionally， mean defect （MD） and mean sensitivity （MS） of visual fields were measured before treatment and on day 14， along with safety evaluation. ResultsAfter treatment， both groups showed significant improvement in BCVA， visual field MD and MS， and TCM syndrome scores （P＜0.05 or P＜0.01）. On day 14 of treatment， the TCM syndrome score in the treatment group was significantly lower than that in the control group （P＜0.05）. There was no significant improvement in optic disc PD and FI， and macular superficial PD and VD after treatment in either group （P＞0.05） except that on day 7 the macular superficial foveal PD in the control group was significantly better than that in the treatment group （P＜0.05）. During the treatment period， no serious adverse events occurred in either group. ConclusionWHTF can improve the visual function indicators including visual acuity and visual field， as well as TCM syndrome scores in atrophic-stage NAION patients with qi deficiency and blood stasis. It shows clinical safety， although it does not appear to have a significant effect on optic disc or macular blood flow.

Objective To analyze the disease burden and trends of bladder cancer in China and globally from 1992 to 2021.  Methods Using the GBD 2021 database, the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates of bladder cancer in China and globally from 1992–2021 were analyzed. Average annual percentage change (AAPC) was calculated using Joinpoint regression. Subgroup analyses by sex and age were conducted, and a Bayesian age-period-cohort (BAPC) model was used to predict trends in age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) for the next 15 years.  Results In 2021, China reported 106 000 new cases (ASIR: 5.14/100 000), 571 000 prevalent cases (age-standardized prevalence rate, ASPR: 26.61/100 000), 43 000 deaths (ASMR: 2.34/100 000), and a DALY rate of 45.31/100 000. From 1992–2021, China showed upward trends in ASIR and ASPR but declines in ASMR and DALYs, while global ASIR, ASMR, and DALYs decreased overall with slow ASPR growth. The peak cases in China and globally were both concentrated in the 65-79 age group, with a significantly higher burden on males than females. In China, smoking-related ASMR and ASDR exceeded global averages and rose, whereas high glucose-related indexes were lower and declined. Projections for 2021–2036 indicated that the global incidence and mortality rates would be rising, but ASIR/ASPR would be declining, while in China, the incidence rate would continue to rise, and the mortality rate will stabilize, with a significant increase in ASIR and a gradual decrease in ASPR.  Conclusion From 1992 to 2021, the incidence of bladder cancer in China has shown a continuous upward trend and is projected to persist in the future, with significant gender and age differences. Particular attention should be given to elderly males aged 85-89. The disease burden of bladder cancer attributable to smoking continues to rise, highlighting the urgent need to strengthen tobacco control policies.

ObjectiveTo investigate the mechanism by which Tianxiang pills （TXP） alleviates myocardial cell pyroptosis in the rat model of myocardial ischemia/reperfusion （I/R） injury through modulating the reactive oxygen species （ROS）/cysteinyl aspartate-specific proteinase-1 （Caspase-1）/gasdermin D （GSDMD） signaling pathway. MethodsA total of 54 SPF-grade adult male Sprague-Dawley rats were randomized into six groups （n=9）： sham （thoracotomy only without ligation）， I/R （left anterior descending coronary artery ligation for 30 min followed by reperfusion）， NAC （positive control， N-acetylcysteine， 150 mg·kg^-1， by gavage）， low-dose Tianxiang pills （TXP-L， 2.5 g·kg^-1， by gavage）］， medium-dose Tianxiang pills （TXP-M， 5 g·kg^-1， by gavage）， and high-dose Tianxiang pills （TXP-H， 10 g·kg^-1， by gavage）. The fluorescent probe method was employed to measure the ROS level. Biochemical assay kits were employed to determine the Caspase-1 activity， superoxide dismutase （SOD） activity， malondialdehyde （MDA） content， and glutathione peroxidase （GSH-Px） activity. Myocardial infarct size was assessed by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Western blot analysis was performed to evaluate the expression levels of proteins in the ROS/Caspase-1/GSDMD pathway， including GSDMD， cleaved Caspase-1/Caspase-1 ratio， the N-terminal domain of GSDMD （GSDMD-N）， and the p22-phox subunit of the reduced nicotinamide adenine dinucleotide phosphate （NADPH） oxidase complex. Enzyme-linked immunosorbent assay （ELISA） was utilized to determine the concentration of interleukin-1β （IL-1β）. Transmission electron microscopy （TEM） was employed to observe mitochondrial structure and to score the degree of mitochondrial swelling. ResultsCompared with the Sham group， the I/R group exhibited elevated the levels of ROS， Caspase-1 activity， GSDMD expression， IL-1β concentration， MDA content， infarct area， mitochondrial swelling score， cleaved Caspase-1/Caspase-1， GSDMD-N， and p22phox and decreased activities of SOD and GSH-Px （P<0.05）. Compared with the I/R group， NAC and different doses of TXP significantly reduced the ROS level， Caspase-1 activity， GSDMD expression， IL-1β concentration， MDA content， infarct area， and mitochondrial swelling score. Moreover， they downregulated the expression of cleaved Caspase-1/Caspase-1， GSDMD-N， and p22phox and increased the activities of SOD and GSH-Px （P<0.05）. Furthermore， TXP exerted effects on ROS， MDA， SOD， GSH-Px， Caspase-1 activity， GSDMD expression， IL-1β concentration， cleaved Caspase-1/Caspase-1， GSDMD-N， p22phox， infarct area， and mitochondrial swelling score in a dose-dependent manner （P<0.05）. ConclusionTianxiang pills alleviates myocardial I/R injury by mitigating oxidative stress and cell pyroptosis through the inhibition of the ROS/Caspase-1/GSDMD signaling pathway.

ObjectiveTo investigate the impact of melanoma-associated antigen D4 （MAGED4） on the malignant biological behavior of hepatocellular carcinoma （HCC）， providing experimental evidence for its evaluation as a potential therapeutic target in HCC. MethodsGenes positively correlated with MAGED4 expression in HCC were screened using the LinkedOmics database， followed by GO functional and KEGG pathway enrichment analyses. Endogenously low-expressing SMMC-7721 and Huh7 cells were selected， with normal hepatic LO2 cells serving as controls. Stable overexpression cell lines were established via lentiviral infection （MAGED4 overexpression group）， with RT-PCR and Western blot validating overexpression efficiency. The effects of MAGED4 overexpression on cell proliferation， cell cycle distribution， migration， and adhesion were systematically analyzed using CCK-8 assays， flow cytometry， scratch healing assays， Transwell migration assays， and cell adhesion assays. ResultsBioinformatics analysis indicated that MAGED4 co-expressed genes were significantly enriched in biological processes closely associated with tumor proliferation and metastasis， including cell-cell adhesion， extracellular matrix organization， and the PI3K-Akt signaling pathway. A stable MAGED4 overexpression cell model was successfully established. In vitro functional assays demonstrated that MAGED4-overexpressing SMMC-7721 and Huh7 cells exhibited a mesenchymal-like morphology， whereas LO2 cells maintained an epithelial-like morphology. Compared with the empty-virus control groups， the MAGED4-overexpressing groups showed significantly increased proliferative activity （48 h： t=3.887， 22.070， 8.866， all P<0.05； 72 h： t=3.231， 23.840， 9.848， all P<0.05； 96 h： t=5.123， 49.800， 5.909， P<0.05， P<0.01， P<0.05）， wound healing rates （12 h： F=40.90， 44.00， 200.50， all P<0.001； 24 h： F=112.00， 34.89， 249.20， all P<0.001）， and numbers of migrated cells （F=239.20， 59.79， 132.80， all P<0.001）， along with significantly decreased numbers of adherent cells （F=73.65， 85.91， 138.00， all P<0.001）， while no significant differences were observed in cell cycle phase distribution in all three cell lines. ConclusionMAGED4 enhances proliferation and migration while suppressing adhesion in both HCC and normal hepatocytes， however， induces mesenchymal-like morphological changes exclusively in HCC cells， suggesting that MAGED4 is capable of driving HCC progression and may serve as a potential therapeutic target for HCC.

Objective To explore the role of neogambogic acid in the characteristics of colorectal cancer stem cells (CRC-CSCs) through the Wnt/β-catenin signaling pathway. Methods The colorectal cells SW480 and HCT166 were divided into control group and neogambogic acid groups (1.5, 3, 6, and 12 μmol/L). The viability of CRC-CSCs was determined by MTT method, and spheroid and clone formation assays were used to assess the capacity of spheroid formation and self-renewal ability of the cells. The effects of neogambogic acid on the apoptosis and cell cycle of CRC-CSCs were evaluated by flow cytometry assays. Real-time quantitative PCR was used to detect the mRNA expression levels of relative markers (CD133, CD44, ALDH1, Oct4, and Nanog) of CRC-CSCs, and the protein expression levels of the self-renewal marker (PCNA), apoptosis markers (cleaved caspase-3 and cleaved caspase-9), and Wnt/β-catenin signaling pathway markers (p-GSK3β, GSK3β, β-catenin, and Wnt) were analyzed using Western blot. Results Compared with the control group, after neogambogic acid treatment, the viability of SW480 and HCT116 cells decreased (P<0.05), the spheroid forming ability and the clone numbers of CRC-CSCs decreased (P<0.001, P<0.01) but the cell apoptosis rate increased (P<0.01), and cell cycle was arrested in G₀/G₁ phase. Moreover, neogambogic acid downregulated the mRNA and protein expression of relative markers of CRC-CSCs (CD133, CD44, ALDH1, Oct4, and Nanog), PCNA, p-GSK3β, β-catenin, and Wnt (P<0.05) and upregulated the expression of cleaved caspase-3, cleaved caspase-9, and GSK3β (P<0.01). Conclusion Neogambogic can inhibit the stem cell properties of colorectal cells via inhibition of Wnt/β-catenin signaling pathway. As a result, neogambogic acid may be an attractive agent against colorectal cancer.

AIM:To evaluate the effectiveness of EYESI binocular indirect ophthalmoscope simulation system as a training platform for fundus examination skills of general practitioner.METHODS:Prospective randomized study. A total of 40 general practitioners who received clinical ophthalmology training at Shenzhen Eye Hospital from January 2021 to December 2024 were selected and randomly divided into two groups by random number table method, with 20 cases in the study group and 20 cases in the control group. The study group was trained by EYESI binocular indirect ophthalmoscope simulation system and the control group was trained by conventional teaching. Training effects of the two groups were analyzed.RESULTS: The general information of the two groups was comparable. Through training with the EYESI binocular indirect ophthalmoscope simulator, the study group showed significant improvements in total examination and drawing scores compared to pre-training results(all P<0.001). Additionally, examination duration, retinal light exposure time, and drawing time were all significantly shorter than those before training(all P<0.001).The study group achieved significantly higher total examination and drawing scores than the control group during the EYESI binocular indirect ophthalmoscope simulator assessment(all P<0.001). Furthermore, examination duration, retinal light exposure time, and drawing time were all significantly shorter in the study group compared to the control group(all P<0.001). Moreover, ratings for the novelty of the training method and overall satisfaction with the training were significantly higher in the study group than in the control group(all P<0.001); while the perceived psychological stress during training was significantly lower in the study group(P<0.001).CONCLUSION:The EYESI binocular indirect ophthalmoscope simulaton system effectively enhances both the proficiency in fundus examination skills and overall training satisfaction among general practitioners.

Based on the pathogenesis of erectile dysfunction (ED) from the meridian-zangfu relationship and the "brain-heart-kidney-essence chamber" axis, it proposes that dysfunction of the "brain-heart-kidney-essence chamber" axis is closely related to the occurrence of ED. Among these, brain-heart disharmony is the key pathogenic factor, kidney deficiency and essence depletion constitute an important basis, and essence chamber stasis is a critical mechanism. The treatment approach emphasizes harmonizing the brain and heart, regulating the mind, tonifying the kidney and replenishing qi, unblocking qi and blood to harmonize the essence chamber. The primary acupoints include Baihui (GV20)-Neiguan (PC6)-Shenmen (HT7), Taixi (KI3)-Guanyuan (CV4)-Sanyinjiao (SP6), and Zhongji (CV3)-Dahe (KI12)-Gongsun (SP4), with additional acupoints selected based on syndrome differentiation. This approach aims to restore the clarity of the brain and heart, replenish kidney qi, and unblock the essence chamber, thereby facilitating the restoration of normal functions of the brain, heart, kidney, and essence chamber, and alleviating ED symptoms and improving overall clinical efficacy.
Humans ; Male ; Meridians ; Erectile Dysfunction/physiopathology* ; Kidney/physiopathology* ; Brain/physiopathology* ; Acupuncture Therapy ; Acupuncture Points ; Heart/physiopathology*

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Objective To establish two osteoarthritis models of destabilization of the medial meniscus(DMM)and chronic ankle instability(CAI)in mice,and compare the effects of knee osteoarthritis with varus deformity on ipsilateral ankle cartilage degeneration.Methods Thirty 6-week-old C57BL/6J male mice were randomly divided into a control group and two surgical groups(DMM group and CAI group),respectively.The progression of ankle joint degeneration was quantitatively evaluated through behavioral observation,imaging techniques and histopathology analysis in each group of mice over a 12-week period.Results A decline in gait stability and balance was observed in two surgical groups.Compared to the control group,the time required to cross the balance beam was increased by 23.20％,and the number of slips was increased by 43.26％at 12th week postoperatively in the DMM group.The bone volume fraction and bone mineral density of ankle joints also increased.Meanwhile,wear and tear of the ankle cartilage were found,with the formation of osteophytes,and OARSI score was increased by 88.89％.These changes in ankle joint were more pronounced in the CAI group.Conclusions This mouse model-based study revealed a coupling relationship between the knee and ankle motion.Knee osteoarthritis with varus deformity could lead to a significant ankle joint degeneration,while the damage was less severe than that observed in CAI.