AIM:To evaluate the clinical efficacy of 0.05% cyclosporine eye drops(Ⅱ)combined with sodium hyaluronate eye drops in treating patients with type 2 diabetes mellitus(T2DM)and moderate-to-severe dry eye.METHODS:A total of 120 T2DM patients(120 eyes)with moderate-to-severe dry eye, treated at the endocrinology and ophthalmology departments at the Affiliated Hospital of Xuzhou Medical University from January 2024 to September 2024, were enrolled in the study. The patients were randomly divided into two groups: combination group [0.05% cyclosporine eye drops(Ⅱ)+ sodium hyaluronate eye drops] and control group(sodium hyaluronate eye drops alone), with 60 cases(60 eyes)in each group. Assessments were conducted at baseline and at 1, 2, and 3 mo post-treatment, including the ocular surface disease index(OSDI), non-contact tear meniscus height(NITMH), first non-invasive tear breakup time(NIBUTf), meibomian gland loss score, lipid layer thickness grade, conjunctival hyperemia grade, and corneal fluorescein staining(FL)score. At 3 mo after treatment, changes in tear inflammatory factors were observed, and corneal subbasal nerve plexus(SBN)morphology/density were analyzed using in vivo confocal microscopy(IVCM).RESULTS:At 1, 2, and 3 mo post-treatment, both groups showed statistically significant increases in NITMH and NIBUTf compared to baseline(all P<0.05), with greater improvement observed in the combination group(both P<0.05). OSDI and FL scores significantly decreased from baseline(all P<0.05), with more pronounced reductions in the combination group(both P<0.05). Meibomian gland loss scores showed no significant improvement in either group(all P>0.05). At 3 mo after treatment, tear levels of interleukin 6(IL-6)and matrix metalloproteinase-9(MMP-9)significantly decreased in both groups(all P<0.001), with a greater reduction noted in the combination group(both P<0.001). The combination group displayed increased corneal nerve branch density and nerve fiber density, along with decreased nerve tortuosity and dendritic cell(DC)density compared to baseline(all P<0.001), while the control group did not show significant changes(all P>0.05).CONCLUSION: The combination of 0.05% cyclosporine eye drops(Ⅱ)and sodium hyaluronate eye drops significantly improves clinical outcomes in T2DM patients with moderate-to-severe dry eye. This treatment effectively alleviates ocular surface inflammation, restores corneal nerve morphology and density, and demonstrates a favorable safety profile.

AIM: To explore the risk factors associated with diabetic retinopathy(DR)based on ultra-widefield swept-source optical coherence tomography angiography(UWF-SS-OCTA), and to establish a clinical prediction model.METHODS:A total of 235 patients(235 eyes)with type 2 diabetes mellitus who were treated in the Affiliated Hospital of Xuzhou Medical University from July to November 2024 were selected as the research objects. According to the presence or absence of DR, they were divided into 120 cases(120 eyes)in non-DR group(NDR group)and 115 cases(115 eyes)in non-proliferative DR group(NPDR group). Data on general characteristics, laboratory tests, and OCTA results were collected for both groups. Univariate analysis was employed to identify DR-related risk factors. Logistic regression analysis was conducted to analyze these risk factors and to establish a DR prediction model. The efficacy of the model was evaluated using the receiver operating characteristic(ROC)curve, calibration curve, and decision curve analysis(DCA).RESULTS: The duration of diabetes, fasting blood glucose, blood urea nitrogen(BUN), history of hypertension, and the choroidal vascular index(CVI)were found to be statistically significant in the model(all P<0.05). Specifically, the duration of diabetes, fasting blood glucose, BUN, and history of hypertension were identified as risk factors for DR among diabetic patients, while CVI was recognized as a protective factor. The area under the curve for the model predicting the probability of DR was 0.898(0.859-0.938), with a diagnostic threshold of 0.438. The corresponding sensitivity and specificity were 87.8% and 78.3%, respectively, indicating that the model possesses high predictive value for the occurrence of DR.CONCLUSION: The duration of diabetes, fasting blood glucose, BUN, history of hypertension, and CVI are significantly correlated with DR. The established prediction model demonstrates a substantial screening capability for DR.

ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

ObjectiveBased on functional near-infrared spectroscopy (fNIRS), we investigated the brain activity characteristics of gross motor tasks in children with autism spectrum disorder (ASD) and motor dysfunctions (MDs) to provide a theoretical basis for further understanding the mechanism of MDs in children with ASD and designing targeted intervention programs from a central perspective. MethodsAccording to the inclusion and exclusion criteria, 48 children with ASD accompanied by MDs were recruited into the ASD group and 40 children with typically developing (TD) into the TD group. The fNIRS device was used to collect the information of blood oxygen changes in the cortical motor-related brain regions during single-handed bag throwing and tiptoe walking, and the differences in brain activation and functional connectivity between the two groups of children were analyzed from the perspective of brain activation and functional connectivity. ResultsCompared to the TD group, in the object manipulative motor task (one-handed bag throwing), the ASD group showed significantly reduced activation in both left sensorimotor cortex (SMC) and right secondary visual cortex (V2) (P<0.05), whereas the right pre-motor and supplementary motor cortex (PMC&SMA) had significantly higher activation (P<0.01) and showed bilateral brain region activity; in terms of brain functional integration, there was a significant decrease in the strength of brain functional connectivity (P<0.05) and was mainly associated with dorsolateral prefrontal cortex (DLPFC) and V2. In the body stability motor task (tiptoe walking), the ASD group had significantly higher activation in motor-related brain regions such as the DLPFC, SMC, and PMC&SMA (P<0.05) and showed bilateral brain region activity; in terms of brain functional integration, the ASD group had lower strength of brain functional connectivity (P<0.05) and was mainly associated with PMC&SMA and V2. ConclusionChildren with ASD exhibit abnormal brain functional activity characteristics specific to different gross motor tasks in object manipulative and body stability, reflecting insufficient or excessive compensatory activation of local brain regions and impaired cross-regions integration, which may be a potential reason for the poorer gross motor performance of children with ASD, and meanwhile provides data support for further unraveling the mechanisms underlying the occurrence of MDs in the context of ASD and designing targeted intervention programs from a central perspective.

OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

The pathogenesis of Alzheimer's disease(AD)is complex and unclear.Existing drugs can only alleviate its symp-toms,and there is an urgent need to develop effective therapeutic drugs.As the representative drugs of tonic and enlightening medicine,ginseng and acorus calamus have pharmacological effects to improve memory,improve learning ability and reduce cognitive impairment,which are commonly used in Chinese med-icine for the treatment of dementia.The combination of ginseng and acorus calamus can further promote the active ingredients in-to brain to exert their medicinal effects,and delay the process of AD through anti-inflammatory,anti-oxidative stress,modulation of neuronal-synaptic plasticity and other multiple pathways,with multi-level,multi-system and multi-target action characteristics.This paper attempts to summarize the existing research results and lay the foundation for further exploring the synergistic mech-anism of action of ginseng-acorus calamus combination and the dose-effect relationship of the combination,so as to provide a sci-entific basis for the development of innovative Chinese medicines for the prevention and treatment of AD.

Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P＜0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P＜0.01);the proportion of CD3+T cells apparently increased(P＜0.05);the level of p16 protein signifi-cantly decreased(P＜0.05);the level of Bcl-2 pro-tein significantly increased(P＜0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P＜0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P＜0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.

N6-methyladenosine(m6A)is the most abundant modification of RNA methylation,dynamically regulated by"writer"and"eraser",regulating the expression of target genes by modulating key biological processes such as mRNA splicing,stability,and translation,after being recognized and combined by"reader".Recent studies have revealed that m6A modifica-tion can regulate the expression of drug-metabolizing enzymes and transporters,consequently affecting the body's drug meta-bolic rate or intracellular drug concentrations,and ultimately in-fluencing therapeutic outcomes.This article reviews the research progress of the molecular mechanism of m6A modification regula-ting drug-metabolizing enzymes and transporters,so as to pro-vide a new idea for rational and personalized clinicaldrug use.

Objective To compare the clinical efficacies of unilateral biportal endoscopy(UBE)technique and percutaneous endoscopic lumbar discectomy(PELD)technique in the treatment of lumbar disc herniation.Methods The clinical data of 149 patients with lumbar disc herniation in our hospital were retrospectively analyzed and divided into the UBE group(n=80)and the PELD group(n=69)according to different surgical methods.The operation time,intraoperative fluoroscopy frequency,intraoperative blood loss,hospital stay,postoperative complications,visual analogue scale(VAS)score,Oswestry disability index(ODI)score,intervertebral disc height and vertebral canal area of the two groups were compared.Results The operation time in the UBE group was longer than that in the PELD group,and the intraoperative fluoroscopy frequency was fewer than that in the PELD group,the differences were statistically significant(P<0.001).There was no significant difference in the intraoperative blood loss or hospital stay between the two groups(P>0.05).There was no significant difference in the VAS or ODI scores at each time point between the two groups(P>0.05).There was no significant difference in the intervertebral disc height or vertebral canal area at each time point between the two groups(P>0.05).The postoperative vertebral canal areas of patients in the two groups were greater than those before surgery,and the differences were statistically significant(P<0.05).The incidence of postoperative complications in the UBE group was lower than that in the PELD group,the difference was statistically significant(P<0.05).Conclusion In terms of short-term efficacy,both PELD technique and UBE technique can effectively relieve the symptoms of low back and leg pain caused by lumbar disc herniation,and the UBE technique has longer operation time,but with fewer intraoperative fluoroscopy frequency,and lower incidence of postoperative complications.