ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

The alternative pathway (AP) of the complement system is a key contributor to the pathogenesis of several diseases including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), C3 glomerular disease (C3G) and age-related macular degeneration (AMD). Complement factor B (CFB) is a trypsin-like serine protein that circulates in the human bloodstream in a latent form. As a key node of the alternative pathway, it is an important target for the treatment of diseases mediated by the complement system. With the successful launch of iptacopan, the CFB small molecule inhibitors has become a current research hotspot, a number of domestic and foreign pharmaceutical companies are actively developing CFB small molecule inhibitors. In this paper, the research progress of CFB small molecule inhibitors in recent years is systematically summarized, the representative compounds and their activities are introduced according to structural types and design ideas, so as to provide reference and ideas for the subsequent research on CFB small molecule inhibitors.

Locomotion, a fundamental motor function encompassing various forms such as swimming, walking, running, and flying, is essential for animal survival and adaptation. The mesencephalic locomotor region (MLR), located at the midbrain-hindbrain junction, is a conserved brain area critical for controlling locomotion. This review highlights recent advances in understanding the MLR’s structure and function across species, from lampreys to mammals and birds, with a particular focus on insights gained from optogenetic studies in mammals. The goal is to uncover universal strategies for MLR-mediated locomotor control. Electrical stimulation of the MLR in species such as lampreys, salamanders, cats, and mice initiates locomotion and modulates speed and patterns. For example, in lampreys, MLR stimulation induces swimming, with increased intensity or frequency enhancing propulsive force. Similarly, in salamanders, graded stimulation transitions locomotor outputs from walking to swimming. Histochemical studies reveal that effective MLR stimulation sites colocalize with cholinergic neurons, suggesting a conserved neurochemical basis for locomotion control. In mammals, the MLR comprises two key nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). Both nuclei contain glutamatergic and GABAergic neurons, with the PPN additionally housing cholinergic neurons. Optogenetic studies in mice by selectively activating glutamatergic neurons have demonstrated that the CnF and PPN play distinct roles in motor control: the CnF drives rapid escape behaviors, while the PPN regulates slower, exploratory movements. This functional specialization within the MLR allows animals to adapt their locomotion patterns and speed in response to environmental demands and behavioral objectives. Similar to findings in lampreys, the CnF and PPN in mice transmit motor commands to spinal effector circuits by modulating the activity of brainstem reticular formation neurons. However, they achieve this through distinct reticulospinal pathways, enabling the generation of specific behaviors. Further insights from monosynaptic rabies viral tracing reveal that the CnF and PPN integrate inputs from diverse brain regions to produce context-appropriate behaviors. For instance, glutamatergic neurons in the PPN receive signals from other midbrain structures, the basal ganglia, and medullary nuclei, whereas glutamatergic neurons in the CnF rarely receive inputs from the basal ganglia but instead are strongly influenced by the periaqueductal grey and inferior colliculus within the midbrain. These differential connectivity patterns underscore the specialized roles of the CnF and PPN in motor control, highlighting their unique contributions to coordinating locomotion. Birds exhibit exceptional flight capabilities, yet the avian MLR remains poorly understood. Comparative studies suggest that the pedunculopontine tegmental nucleus (PPTg) in birds is homologous to the mammalian PPN, which contains cholinergic neurons, while the intercollicular nucleus (ICo) or nucleus isthmi pars magnocellularis (ImC) may correspond to the CnF. These findings provide important clues for identifying the avian MLR and elucidating its role in flight control. However, functional validation through targeted experiments is urgently needed to confirm these hypotheses. Optogenetics and other advanced techniques in mice have greatly advanced MLR research, enabling precise manipulation of specific neuronal populations. Future studies should extend these methods to other species, particularly birds, to explore unique locomotor adaptations. Comparative analyses of MLR structure and function across species will deepen our understanding of the conserved and evolved features of motor control, revealing fundamental principles of locomotion regulation throughout evolution. By integrating findings from diverse species, we can uncover how the MLR has been adapted to meet the locomotor demands of different environments, from aquatic to aerial habitats.

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

Objective: To explore two visual acuity standards for examining uncorrected visual acuity (UCVA) to define poor vision in lower grade elementary school students, and to compare the difference of screening myopia rates when combined with non cycloplegic auto refraction (NCAR), so as to provide a scientific basis for standardizing UCVA examination methods using CAR as the gold standard of authenticity and reliability. Methods: From March 22nd to April 9th, 2023, a total of 549 first and second grade students aged 7-8 years from a primary school in Hefei City were selected for the study by convenient cluster sampling method. Two methods were employed for UCVA examination:the first method involved charts where the student could not make mistakes in identifying at least half of the characters per line (V1), and the second method used charts with character sizes ranging from 4.0 -4.5, 4.6-5.0 and 5.1-5.3, without allowing 1, 2 and 3 errors per line (V2). While NCAR was performed, then 187 students underwent CAR examination. Paired Wilcoxon rank-sum test and McNemar test were used to compare the differences between V1 and V2 methods in defining poor vision and screening myopia rates. Using CAR as the gold standard, the authenticity and reliability of defining screening myopia rates through the combination of V1 and V2 methods along with NCAR were evaluated. Results: The UCVA examination results for V1 and V2 showed statistically significant differences in both the right eye [5.0(4.9,5.0), 4.9(4.8,5.0)] and the left eye [ 5.0 (4.9,5.0), 4.9(4.8,5.0)] ( Z=-13.95, -13.34, P <0.01). The detection rates of poor vision for the right eye were 43.53% for V1 and 63.21% for V2, and the left eye with 44.08% for V1 and 62.11% for V2, with statistically significant differences ( χ 2= 106.01 , 95.09, P <0.01). When screening myopia rates were assessed for UCNA methods combined with NCAR, the right eye rates were 21.49% for V1 and 24.59% for V2, and the left eye rates were 21.31% for V1 and 23.13% for V2, with statistically significant differences ( χ 2=15.06, 8.10, P <0.01). Using CAR as the gold standard, the detection rates in the right eye and left eye were 16.58 % and 17.11%, respectively. The Youden indices for defining screening myopia in the right eye were 0.80 for V1 and 0.79 for V2, and the left eye with 0.85 for V1 and 0.83 for V2. The agreement rates for the right eye were 91.98 % for V1 and 89.30% for V2, and the left eye with 94.12% for V1 and 91.98% for V2. The Kappa values for the right eye were 0.73 for V1 and 0.67 for V2, and the left eye with 0.81 for V1 and 0.75 for V2. Conclusions Authenticity and reliability of two UCVA examination methods combined with NCAR in defining screening myopia are higher in V1 than V2 methods. It is recommended to unify the visual acuity examination methods by requiring the correct identification of more than half of the total number of visual markers in a row.

Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.

Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart dis-ease,such as acute or chronic myocardial ischemic changes,sometimes make it difficult to locate the ischemic site due to the short death process,the lack of tissue reaction time.In some cases,the de-ceased died of sudden death on the first-episode,resulting in difficulty for medical examiners to make an accurate diagnosis.However,clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process.This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medi-cal research,including plaque rupture,plaque erosion and calcified nodules,as well as the influencing factors leading to plaque instability,and briefly describes the research progress and technique of the atherosclerotic plaques,in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different patho-logic states of coronary atherosclerotic plaques.

Objective To observe the clinical efficacy of thumb-tack needling for subcutaeous embedding combined with joint mobilization in the treatment of post-stroke shoulder-hand syndrome.Methods A total of 80 patients with post-stroke shoulder-hand syndrome were randomly divided into a treatment group and a control group,with 40 patients in each group.Both groups were given arthrocentesis,the control group was given ordinary acupuncture on the basis of arthrocentesis,and the treatment group was combined with thumb-tack needling for subcutaeous embedding.One course of treatment was 4 weeks and a total of 4 weeks of treatment was given.After 1 month of treatment,the clinical efficacy of the two groups was evaluated.The changes of Visual Analogue Scale(VAS)of pain scores and simplified Fugl-Meyer Assessment(FMA)scores,as well as the pain-free passive forward flexion and abduction of the shoulder joint of the affected limb were observed before and after treatment.The Simple Quality of Life Scale(SF-36)scores of the patients in the two groups were compared after treatment.The safety and the occurrence of adverse reactions in the two groups were also evaluated.Results(1)The total effective rate was 95.00%(38/40)in the treatment group and 80.00%(32/40)in the control group.The efficacy of the treatment group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the VAS scores and upper extremity FMA scores of the patients in the two groups were significantly improved(P＜0.05),and the treatment group was significantly superior to the control group in improving the VAS scores and upper extremity FMA scores,and the differences were statistically significant(P＜0.05).(3)After treatment,the joint mobility of patients in the two groups were significantly improved(P＜0.05),and the improvement of shoulder joint movement in the treatment group was superior to that in the control group,and the difference was statistically significant(P＜0.05).(4)After treatment,the SF-36 Quality of Life Scale scores of the treatment group were significantly superior to those of the control group in terms of physical function,psychological function,emotional health,and social function levels,and the difference was statistically significant(P＜0.05).(5)There was no significant difference in the incidence of adverse reactions between the treatment group and the control group(P＞0.05).Conclusion Thumb-tack needling for subcutaeous embedding combined with joint mobilization exert certain effect in the treatment of post-stroke shoulder-hand syndrome.It can significantly improve the pain symptoms of patients,thus improving their quality of life,and the clinical effect is remarkable.

BACKGROUND:Pulsed electromagnetic fields,as an important physical therapy,are exactly effective in the treatment of osteoarthritis,but the mechanism has not been fully clarified. OBJECTIVE:To observe the effect of pulsed electromagnetic field on the degeneration of knee joint cartilage in aged rats. METHODS:Eight 6-month-old Sprague-Dawley rats were selected as the young group and were subjected to normal diet with no treatment.Sixteen 22-month-old Sprague-Dawley rats were randomly divided into old group(n=8)and pulsed electromagnetic field group(n=8).The rats in the pulsed electromagnetic field group were subjected to a pulsed electromagnetic field intervention,once a day,5 days per week for continuous 8 weeks.The rats in the old group were given no treatment.All rats were anesthetized and executed after 8 weeks for the detection of relevant indexes. RESULTS AND CONCLUSION:Compared with the young group,serum type Ⅱ collagen C-terminal peptide level was increased in the old group(P<0.05);compared with the old group,serum type Ⅱ collagen C-terminal peptide level was decreased in the pulsed electromagnetic field group(P<0.05).Micro-CT showed that the bone volume fraction,bone mineral density,and number of bone trabeculae decreased(P<0.05)and the trabecular separation increased(P<0.05)in the tibia of rats in the aged group compared with the young group;and the bone volume fraction,bone density,and number of trabeculae increased(P<0.05)and the trabecular separation decreased(P<0.05)in the tibia of rats in the pulsed electromagnetic field group compared with the aged group.The tibial plateau Safranin O-fast green staining showed that the articular cartilage structure of rats in the aged group was disorganized,and the number of chondrocytes was obviously reduced,and the tidal line could not be distinguished.The above results were improved in the pulsed electromagnetic field group.RT-qPCR and western blot assay showed that the mRNA and protein expression levels of matrix metalloproteinase 1,matrix metalloproteinase 13,P53 and P21 in the articular cartilage and subchondral bone of rats were elevated in the aged group compared with the young group(P<0.05)and decreased in the pulsed electromagnetic field group compared with the old group(P<0.05).To conclude,pulsed electromagnetic fields may improve osteoarthritis in aged rats by inhibiting chondrocyte senescence,alleviating articular cartilage degradation and inhibiting subchondral bone osteoporosis through suppressing the expression of P53/P21.

Objective To evaluate the characteristics of different antigen-specific T cell immune responses to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)after inoculation with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months.Methods Fifteen healthy adults were enrolled in this study and blood samples collected at 12 months after receiving two doses of SARS-CoV-2 inactivated vaccine.The level and phenotypic characteristics of SARS-CoV-2 antigen-specific T lymphocytes were detected by activation-induced markers(AIM)based on polychromatic flow cytometry.Results After 12 months of inoculation with 2 doses of SARS-CoV-2 inactivated vaccine,more than 90%of adults had detectable Spike and Non-spike antigen-specific CD4+ T cells immune responses(Spike:14/15,P=0.0001;Non-spike:15/15,P<0.0001).80%of adults had detectable Spike and Non-spike antigen-specific CD8+ T cells immune responses(Spike:12/15,P=0.0463;Non-spike:12/15,P=0.0806).Antigen-specific CD4+ T cells induced by SARS-CoV-2 inactivated vaccination after 12 months were composed of predominantly central memory(CM)and effector memory 1(EM1)cells.On the other hand,in terms of helper subsets,antigen-specific CD4+ T cells mainly showed T helper 1/17(Th1/17)and T helper 2(Th2)phenotypes.Conclusions SARS-CoV-2 inactivated vaccination generates durable and extensive antigen-specific CD4+ T cell memory responses,which may be the key factor for the low proportion of severe coronavirus disease 2019(COVID-19)infection in China.