Diabetic retinopathy（DR）， as one of the most common and serious microvascular complications of diabetes mellitus， seriously threatens human health， and belongs to "Xiaoke eye diseases" in traditional Chinese medicine（TCM）， which has been richly experienced by medical practitioners through the ages， but is mostly recorded in a piecemeal manner and has not been systematically researched. This disease is featured by long course and repeated attack， and is refractory， which belongs to the research category of "persistent illness entering collaterals". Systematic establishment of TCM collateral disease theory for guiding prevention and treatment of DR has important clinical value. On the basis of close correlation between tertiary collaterals at the terminal of collaterals and capillaries and microcirculation， the concept of "tertiary collaterals-microvascular" is proposed. It is pointed out that DR falls within the scope of "tertiary collaterals-microvascular" diseases， and presents four types of micro-pathological characteristics， including stasis， insufficiency， growth and bleeding of tertiary collaterals. It is concluded that "deficiency of both Qi and Yin" is the basic pathogenesis of DR， and "blood stasis and collateral obstruction" is the important pathogenesis and key factor. Thus， the treatment method of "dispersing blood stasis， dredging collateral， tonifying Qi and Yin， stopping hemorrhage and improving eyesight" is determined， and the formula of Tongluo Mingmu capsules is developed. The article tightly focuses on the pathological changes such as stasis， growth， insufficiency and bleeding of collaterals， addresses both symptoms and root causes， and plays a synergistic role of both dispersing stasis and stopping bleeding. In this way， it can realize the purpose of tonifying Qi and Yin to replenish the essence， dispersing stasis and dredging collaterals to meet the requirement， as well as stopping hemorrhage and improving eyesight to deal with changes. Fundamental researches demonstrate that Tongluo Mingmu capsules has synergy effects of protecting both retinal capillaries and retinal cells. Phase-Ⅲ clinical trial of new drug has proven definite clinical efficacy and good safety， which provides a new drug choice for enhancing clinical effect of DR， and further supports the scientific value of Luobing theory in preventing and treating DR and other clinically significant diseases.

ObjectiveThe controllability changes of structural brain network were explored based on the control and brain network theory in young smokers, this may reveal that the controllability indicators can serve as a powerful factor to predict the sleep status in young smokers. MethodsFifty young smokers and 51 healthy controls from Inner Mongolia University of Science and Technology were enrolled. Diffusion tensor imaging (DTI) was used to construct structural brain network based on fractional anisotropy (FA) weight matrix. According to the control and brain network theory, the average controllability and the modal controllability were calculated. Two-sample t-test was used to compare the differences between the groups and Pearson correlation analysis to examine the correlation between significant average controllability and modal controllability with Fagerström Test of Nicotine Dependence (FTND) in young smokers. The nodes with the controllability score in the top 10% were selected as the super-controllers. Finally, we used BP neural network to predict the Pittsburgh Sleep Quality Index (PSQI) in young smokers. ResultsThe average controllability of dorsolateral superior frontal gyrus, supplementary motor area, lenticular nucleus putamen, and lenticular nucleus pallidum, and the modal controllability of orbital inferior frontal gyrus, supplementary motor area, gyrus rectus, and posterior cingulate gyrus in the young smokers’ group, were all significantly different from those of the healthy controls group (P<0.05). The average controllability of the right supplementary motor area (SMA.R) in the young smokers group was positively correlated with FTND (r=0.393 0, P=0.004 8), while modal controllability was negatively correlated with FTND (r=-0.330 1, P=0.019 2). ConclusionThe controllability of structural brain network in young smokers is abnormal. which may serve as an indicator to predict sleep condition. It may provide the imaging evidence for evaluating the cognitive function impairment in young smokers.

OBJECTIVE To investigate the mechanism of gossypol acetic acid （GAA） in the treatment of uterine fibroids. METHODS Human leiomyoma cells SK-UT-1 were selected as objects to investigate the effects of different concentrations （5， 10， 20， 40， 80， 160 μmol/L） of GAA on the activities of cell proliferation. 4D-DIA proteomic detection and bioinformatics analysis were carried out to screen differential proteins. Gene ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathway analysis were performed. The expressions of top 3 proteins [N-myc downstream regulated gene 1 （NDRG1）， epidermal growth factor receptor feedback inhibitor 1 （ERRFI1）， CXC chemokine ligand 3 （CXCL3）] with differential fold changes in SK-UT-1 cells were determined. RESULTS 10-160 μmol/L GAA could significantly reduce the survival rate of SK- UT-1 cells （P＜0.05）. Proteomics results showed that a total of 921 differentially expressed proteins were obtained， including 254 up-regulated proteins and 667 down-regulated proteins. The differentially expressed proteins were mainly distributed in mitochondria， nucleus， extracellular matrix， etc. Bioinformatics results showed that differentially expressed proteins were mainly involved in signaling pathways such as PI3K/AKT （phosphoinositide 3-kinase/protein kinase B）， MAPK （mitogen-activated protein kinase）， TNF （tumor necrosis factor）， etc.， which mainly involved cell apoptosis， aging， and movement. GAA significantly decreased protein expressions of NDRG1 and CXCL3 （P＜0.05）， but increased protein expression of ERRFI1 （P＜0.05）. CONCLUSIONS The improvement effect of GAA on uterine fibroids may involve signaling pathways such as PI3K/AKT， MAPK， TNF， etc. It can improve the occurrence and development of uterine fibroids by downregulating the expressions of NDRG1 and CXCL3 proteins， upregulating the expression of ERRFI1 protein， and affecting the proliferation and apoptosis of uterine fibroid cells.

AIM: To assess the clinical efficacy and safety of epithelial-off accelerated corneal collagen cross-linking(CXL)in the management of progressive keratoconus over 1 a period.METHODS:A retrospective pre-post self-controlled study. Data were collected from complete cases of 63 patients(84 eyes)with progressive keratoconus who underwent epithelial-off accelerated CXL between August 2018 and September 2021. Uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), refraction, corneal transparency, maximum keratometry(Kmax)of the anterior corneal surface, minimum corneal thickness, endothelial cell counts, and intraocular pressure(IOP)were analyzed preoperatively and at 1, 3, 6, and 12 mo postoperatively.RESULTS:No significant differences were observed in UCVA and spherical power before and after surgery(all P>0.05). However, there were significant differences in BCVA, cylinder power, Kmax, minimum corneal thickness, and IOP(all P<0.05). At 12 mo postoperatively, there were no significant differences in BCVA, cylinder power, minimum corneal thickness, and IOP compared with preoperative values(all P>0.05), while Kmax was decreased compared with preoperative value(P<0.05). At 1 mo postoperatively, the corneal endothelial cell count(2519.87±345.28 cells/mm2)was decreased compared with preoperative value(2693.63±313.39 cells/mm2; P<0.001). At 1 wk postoperatively, 22 eyes developed corneal haze(grade 0.5 to 1), and 15 eyes presented with linear corneal stromal opacity at 1 mo postoperatively. In 7 eyes, corneal opacity subsided within 3 to 6 mo after the operation, however, 5 eyes still exhibited corneal nebula or macula without affecting visual acuity.CONCLUSION: After epithelial-off accelerated CXL, the UCVA, BCVA and spherical diopter of patients remained stable over time. The astigmatism and corneal curvature temporarily increased and then gradually decreased. The cornea minimum thickness decreased initially but subsequently returned to preoperative levels. The corneal curvature at 6 and 12 mo after surgery was significantly lower than that before surgery, which could effectively prevent the progression of keratoconus. Despite potential localized corneal opacity and macular complications, as well as a possible decrease in corneal endothelial cell count, BCVA remained unaffected, demonstrating favorable safety outcomes.

AIM: To assess the clinical efficacy and safety of epithelial-off accelerated corneal collagen cross-linking(CXL)in the management of progressive keratoconus over 1 a period.METHODS:A retrospective pre-post self-controlled study. Data were collected from complete cases of 63 patients(84 eyes)with progressive keratoconus who underwent epithelial-off accelerated CXL between August 2018 and September 2021. Uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), refraction, corneal transparency, maximum keratometry(Kmax)of the anterior corneal surface, minimum corneal thickness, endothelial cell counts, and intraocular pressure(IOP)were analyzed preoperatively and at 1, 3, 6, and 12 mo postoperatively.RESULTS:No significant differences were observed in UCVA and spherical power before and after surgery(all P>0.05). However, there were significant differences in BCVA, cylinder power, Kmax, minimum corneal thickness, and IOP(all P<0.05). At 12 mo postoperatively, there were no significant differences in BCVA, cylinder power, minimum corneal thickness, and IOP compared with preoperative values(all P>0.05), while Kmax was decreased compared with preoperative value(P<0.05). At 1 mo postoperatively, the corneal endothelial cell count(2519.87±345.28 cells/mm2)was decreased compared with preoperative value(2693.63±313.39 cells/mm2; P<0.001). At 1 wk postoperatively, 22 eyes developed corneal haze(grade 0.5 to 1), and 15 eyes presented with linear corneal stromal opacity at 1 mo postoperatively. In 7 eyes, corneal opacity subsided within 3 to 6 mo after the operation, however, 5 eyes still exhibited corneal nebula or macula without affecting visual acuity.CONCLUSION: After epithelial-off accelerated CXL, the UCVA, BCVA and spherical diopter of patients remained stable over time. The astigmatism and corneal curvature temporarily increased and then gradually decreased. The cornea minimum thickness decreased initially but subsequently returned to preoperative levels. The corneal curvature at 6 and 12 mo after surgery was significantly lower than that before surgery, which could effectively prevent the progression of keratoconus. Despite potential localized corneal opacity and macular complications, as well as a possible decrease in corneal endothelial cell count, BCVA remained unaffected, demonstrating favorable safety outcomes.

Lactate, with a chemical formula of C₃H₆O₃, is an intermediate product of glucose metabolism in the body and a raw material for hepatic gluconeogenesis. Under physiological resting conditions, the body mainly relies on aerobic oxidation of sugar and fat for energy supply, so the blood lactate concentration is lower. However, during exercise, the enhanced glycolysis in skeletal muscles leads to the significant release of lactate into the bloodstream, causing a marked increase in blood lactate concentration. Traditionally, lactate has been regarded as a metabolic waste product of glycolysis and a contributor to exercise-induced fatigue. Nevertheless, recent studies have revealed that, in humans, lactate is a major vehicle for carbohydrate carbon distribution and metabolism, serving not only as an energy substance alongside glucose but also as a vital component in various biological pathways involved in cardiac energetics, muscle adaptation, brain function, growth and development, and inflammation therapy. Two primary pathways can elevate lactate levels in neurons during exercise. One is peripheral skeletal muscle-derived lactate, which can enter the bloodstream and cross the blood-brain barrier into the brain with the assistance of monocarboxylate transporters (MCTs) from the solute carrier family 16 (SLC16). The other is the central brain-derived pathway. During exercise, neuronal activity is enhanced, promoting the secretion of neuroactive substances such as glutamate, norepinephrine, and serotonin in the brain. This activates astrocytes to break down glycogen into lactate and stimulates glutamate from the presynaptic terminal into the synaptic cleft. It upregulates the glucose transport protein-1 (GLUT-1) expression, allowing astrocytes to convert glucose into lactate through glycolysis. The lactate is produced via peripheral pathways and central pathways during exercise are transported by astrocyte membrane monocarboxylate transporters MCT1 and MCT4 to the extracellular space, where neurons take it up through neuronal cell membrane MCT2. The lactate in neurons can serve as an alternative energy source of glucose for neuronal functional activities, meeting the increased energy demands of synaptic activity during exercise, and maintaining energy balance and normal physiological function in the brain. Additionally, acting as a signaling molecule lactate can enhance synaptic plasticity through the SIRT1/PGC-1α/FNDC5 and ERK1/2 signaling pathways, lactate can promote angiogenesis by upregulating VEGF-A expression through the PI3K/Akt and ERK1/2 signaling pathways, stimulate neurogenesis via the Akt/PKB signaling pathway, and reduce neuroinflammation through activation of the “lactate timer”. Overall, lactate contributes to the protection of neurons, the promotion of learning and memory, the enhancement of synaptic plasticity, and the reduction of neuroinflammation in the nervous system. While lactate may serve as a potential mediator for information exchange between the peripheral and central nervous systems during exercise, further experimental research is needed to elucidate its action mechanisms in the nervous system. In addition, future studies should utilize advanced neurophysiological and molecular biology techniques to uncover the importance of lactate in maintaining brain function and preventing neurological diseases. Accordingly, this article first reviews the historical research on lactate, then summarizes the metabolic characteristics and neuronal sources of lactate, and finally explores the role and mechanisms of exercise-induced lactate in the nervous system, aiming to provide new perspectives and targets for understanding the mechanisms underlying exercise promotion of brain health.

BACKGROUND:Human periodontal ligament stem cells are potential functional cells for periodontal tissue engineering.However,long-term in vitro culture may lead to reduced stemness and replicative senescence of periodontal ligament stem cells,which may impair the therapeutic effect of human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of oxymatrine on the stemness maintenance and osteogenic differentiation of periodontal ligament stem cells in vitro,and to explore the potential mechanism. METHODS:Periodontal ligament stem cells were isolated from human periodontal ligament tissues by tissue explant enzyme digestion and cultured.The surface markers of mesenchymal cells were identified by flow cytometry.Periodontal ligament stem cells were incubated with 0,2.5,5,and 10 μg/mL oxymatrine.The effect of oxymatrine on the proliferation activity of periodontal ligament stem cells was detected by CCK8 assay.The appropriate drug concentration for subsequent experiments was screened.Western blot assay was used to detect the expression of stem cell non-specific proteins SOX2 and OCT4 in periodontal ligament stem cells.qRT-PCR and western blot assay were used to detect the expression levels of related osteogenic genes and proteins in periodontal ligament stem cells. RESULTS AND CONCLUSION:(1)The results of CCK8 assay showed that 2.5 μg/mL oxymatrine significantly enhanced the proliferative activity of periodontal stem cells,and the subsequent experiment selected 2.5 μg/mL oxymatrine to intervene.(2)Compared with the blank control group,the protein expression level of SOX2,a stem marker of periodontal ligament stem cells in the oxymatrine group did not change significantly(P>0.05),and the expression of OCT4 was significantly up-regulated(P<0.05).(3)Compared with the osteogenic induction group,the osteogenic genes ALP,RUNX2 mRNA expression and their osteogenic associated protein ALP protein expression of periodontal ligament stem cells were significantly down-regulated in the oxymatrine+osteogenic induction group(P<0.05).(4)The oxymatrine up-regulated the expression of stemness markers of periodontal ligament stem cells and inhibited the bone differentiation of periodontal ligament stem cells,and the results of high-throughput sequencing showed that it may be associated with WNT2,WNT16,COMP,and BMP6.

ObjectivePatients with hepatic glycogen storage disease（GSD）have recurrent episodes of hypoglycemia. This study aimed to investigate and analyze blood glucose and biochemical indicators in pediatric patients with hepatic GSD， thus provide data support for hypoglycemia prevention and its clinical management. MethodsA cross-sectional field study was conducted among patients with hepatic GSD treated in the Department of Pediatrics of Guangdong Provincial People's Hospital on July 14， 2024. We collected the peripheral blood samples of the patients and their healthy family controls on site， then analyzed and compared their blood glucose and biochemical indicators. ResultsOf the 44 patients with hepatic GSD， there were 34 males and 10 females， including GSD Ib（n =14）， GSD Ia（n=15）， GSD Ⅲ（n=2）， GSD Ⅵ（n=7）and GSD Ⅸ（n=6）. The average age was 7.60（5.08-11.98）years. All patients were on uncooked cornstarch（UCCS）therapy. Of the patients， 77.3%（34/44）had hepatomegaly， 61.4%（27/44）had recurrent hypoglycemia， 61.4%（27/44）had blood glucose ≤ 3.9 mmol/L， 18.2%（8/44）had blood glucose ≤ 2.8 mmol/L， and none of the 8 cases was GSD Ib. The lowest blood glucose level was 1.19 mmol/L and no episodes of hypoglycemia occurred. Of the family control subjects， 65.9%（29/44）had blood glucose ≤ 3.9 mmol/L. There was no significant difference in hypoglycemia prevalence between hepatic GSD group and control group（P=0.658）. The hepatic GSD patients had hyperlactacemia， hyperuricemia and hypercholesterolemia prevalence rates of 65.9%， 45.5% and 9.1%， respectively， as compared with 18.2%， 43.2% and 15.9%， respectively， for the family control subjects. No significant difference was found in the prevalence rates of hyperuricemia and hypercholesterolemia between the two groups（P=0.830 and P=0.334， respectively）. ConclusionsAsymptomatic hypoglycemia is common in patients with hepatic GSD， especially in non-GSD-Ib patients. It is necessary to optimize the diet management of UCCS， conduct dynamic blood glucose monitoring and follow a light diet， so as to decrease hyperuricemia and hypercholesterolemia， avoid and reduce the serious adverse reactions and complications caused by severe hypoglycemia.

In this study, we constructed a GLP-2R-HEK293 cell line and established a method for the determination of the in vitro biological activity of teduglutide based on HTRF, after optimizing experimental conditions and methodological verification. We also carried out relative potency detection of teduglutide pharmaceutical products using this method. The result showed that there was a quantitative-efficient relationship between the teduglutide activity and cAMP contents in GLP-2R-HEK293 cells, which conformed to four-parameter model. Method verification results of five concentrations of teduglutide (64%, 80%, 100%, 125% and 156%) met the requirements of the General Rules of Chinese Pharmacopoeia, 2020 edition, Volume IV (9401). We then analyzed the relative potency of three batches of teduglutide drug substances and three batches of drug products. The linearity, regression and parallelism of the obtained curves all fit the system suitability requirements. The relative potency of six batches of teduglutide was from 83% to 105%. In summary, the biological activity detection method established in this study was accurate, precise, simple and time-saving, which can be used for quality control of teduglutide pharmaceutical products.

ObjectiveTo understand the development stages and use of policy tools of general practitioner policies in China since it was first proposed, to summarize the experience and explore the shortcomings, so as to provide references for the adjustment and optimization of China’s general practitioner policies. MethodsContent analysis and mathematical statistics analysis were used to conduct a quantitative research on 111 policy documents with 422 policy items involving general practitioners at the national level from 1997 to 2023, through a three-dimensional analysis framework integrating policy tools, human capital process and policy development stages. ResultsCapacity‑building policy tools were most frequently used in general practitioner policies, and the policy tools gradually shifted from mandate to inducement. The general practitioner policies paid less attention to the career selection link, but paid full attention to every segment of human capital links, with a comprehensive application of policy tools observed in the integrated development stage, despite the existence of unbalanced internal distribution. ConclusionIt is suggested to promote the use of incentive policy tools and to explore multiple approaches based on incentive theory; pay attention to the career selection link for guiding the employment of general practitioners; take the appropriateness between the policy tools and human capital process into comprehensive consideration, striking a dynamic balance of the internal structure of general practitioner policies.