AIM: To analyze the changes of retinal structure and function before and after panretinal photocoagulation(PRP)in patients with proliferative diabetic retinopathy(PDR).METHODS: Prospective study. Totally 98 cases(98 eyes)of PDR patients who underwent PRP in Eye Hospital of Wenzhou Medical University from January 2022 to May 2023 were included. Optical coherence tomography angiography(OCTA)was used to detect central retinal thickness(CRT), central macular thickness(CMT), subfoveal choroidal thickness(SFCT), foveal avascular zone(FAZ), deep vascular complex(DVC)blood flow density, superficial vascular complex(SVC)blood flow density before and at 1 wk, 1 and 3 mo after PRP. During the follow-up, 1 eye underwent vitrectomy, 2 eyes were lost to follow-up, and finally 95 eyes completed 1 a follow-up, with a loss rate of 3%. According to the visual prognosis at 1 a after treatment, the patients were divided into two groups: 73 eyes in good prognosis group and 22 eyes in poor prognosis group(including 9 eyes of visual disability and 13 eyes of visual regression). The changes in retinal structure and function before and after PRP treatment were compared between the two groups of patients, and the receiver operating characteristic(ROC)curve and decision curve were used to analyze the predictive value of retinal structure and function for PDR treatment.RESULTS: There were statistical significant differences in PDR staging, CRT, CMT, SFCT, DVC blood flow density, and SVC blood flow density between the two groups of patients before treatment(all P<0.05). At 1 wk, 1 and 3 mo after treatment, the FAZ area of both groups decreased compared to before treatment, while the blood flow density of DVC and SVC increased compared to before treatment(both P<0.05). However, there was no significant difference in the blood flow density of FAZ, DVC, and SVC between the two groups at 1 wk, 1 and 3 mo after treatment(all P>0.05). The CRT, CMT and SFCT of the two groups at 1 wk after treatment were higher than those before treatment(all P<0.05), but there were no significant differences between the two groups(all P>0.05). The CRT, CMT and SFCT at 1 and 3 mo after treatment were lower than those at 1 wk after treatment and before treatment in both groups. The CRT, CMT and SFCT in the poor prognosis group at 3 mo after treatment were higher than those at 1 mo after treatment, and were higher than those in the good prognosis group(all P<0.05). ROC analysis showed that, at 3 mo after laser treatment in PDR patients, the area under the curve of the CRT, CMT, and SFCT alone or in combination after treatment for 1 a was 0.788, 0.781, 0.783, and 0.902, respectively, and the combined prediction value was better(P<0.05). Decision curve analysis showed that the combined detection of CRT, CMT, and SFCT in PDR patients at 3 mo after treatment can improve the predictive value of visual prognosis.CONCLUSION: The optimal time for retinal structure and function recovery in PDR patients after PRP treatment is between 1 wk and 1 mo. OCTA measurement of CRT, CMT, and SFCT at 3 mo after treatment can predict the visual prognosis during the 1 a treatment period.

OBJECTIVES: The gut microbiota plays a crucial role in the pathophysiology of various types of diabetes. However, the causal relationship between them has yet to be systematically elucidated. This study aims to explore the potential causal associations between gut microbiota and diabetes using a two-sample Mendelian randomization (MR) analysis, based on multiple taxonomic levels. METHODS: Eligible instrumental variables were extracted from the selected genome-wide association study (GWAS) data on gut microbiota. These were combined with GWAS datasets on type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes mellitus (GDM) to conduct forward MR analysis, sensitivity analysis, reverse MR analysis, and validation of significant estimates. Microbial taxa with causal effects on T1D, T2D, and GDM were identified based on a comprehensive assessment of all analytical stages. RESULTS: A total of 2 179, 2 176, and 2 166 single nucleotide polymorphisms (SNP) were included in the MR analyses for gut microbiota with T1D, T2D, and GDM, respectively. MR results indicated causal associations between: Six microbial taxa (Eggerthella, Lachnospira, Bacillales, Desulfovibrionales, Parasutterella, and Turicibacter) and T1D; 9 microbial taxa (Verrucomicrobia, Deltaproteobacteria, Actinomycetales, Desulfovibrionale, Actinomycetaceae, Desulfovibrionaceae, Actinomyces, Alcaligenaceae, and Lachnospiraceae NC2004 group) and T2D; 10 microbial taxa (Betaproteobacteria, Coprobacter, Ruminococcus2, Tenericutes, Clostridia, Methanobacteria, Mollicutes, Methanobacteriales, Methanobacteriaceae, and Methanobrevibacter) and GDM. CONCLUSIONS This study identified specific gut microbial taxa that may significantly increase or decrease the risk of developing diabetes. Some findings were fully replicated in independent validation datasets. However, the underlying biological mechanisms of these causal relationships warrant further investigation through mechanistic studies and population-based research.
Gastrointestinal Microbiome/genetics* ; Humans ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Diabetes Mellitus, Type 2/genetics* ; Diabetes Mellitus, Type 1/genetics* ; Female ; Polymorphism, Single Nucleotide ; Diabetes, Gestational/genetics* ; Pregnancy

ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan （LW） on mitochondrial damage in the Alzheimer's disease （AD） model of Caenorhabditis elegans （C. elegans）. MethodC. elegans transfected with human β-amyloid protein （Aβ） _1-42 gene was used as an AD model. The rats were divided into blank group， model group， metformin group （50 mmol·L^-1）， and low， medium， and high dose （1.04， 2.08， 4.16 g·kg^-1） LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine （5-HT） in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate （ATP） kit， and mitochondrial membrane potential was detected by the JC-1 method. In addition， the mRNA expression of Aβ expression gene （Amy-1）， superoxide dismutase-1 （SOD-1）， mitochondrial transcription factor A homologous gene-5 （HMG-5）， mitochondrial power-associated protein 1 （DRP1）， and mitochondrial mitoprotein 1 （FIS1） was detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT （P<0.05） and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group， in the model group， the mRNA expression of Aβ protein and Amy-1 increased （P<0.01）， and the mRNA expression of SOD-1 and HMG-5 decreased （P<0.01）. The mRNA expression of DRP1 and FIS1 increased （P<0.01）， and the level of mitochondrial membrane potential decreased （P<0.05）. The content of ATP decreased （P<0.01）. Compared with the model group， in the positive medicine group and medium and high dose LW groups， the mRNA expression of Aβ protein and Amy-1 decreased （P<0.05，P<0.01）， and the mRNA expression of SOD-1 and HMG-5 increased （P<0.01）. The mRNA expression of DRP1 decreased （P<0.05，P<0.01）， and that of FIS1 decreased （P<0.01）. The level of mitochondrial membrane potential increased （P<0.01）， and the content of ATP increased （P<0.05，P<0.01）. ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria， protect mitochondrial DNA， reduce the fragmentation of mitochondrial division， repair the damaged mitochondria， adjust the mitochondrial membrane potential， restore the level of neuronal ATP， and reduce the neuronal damage caused by Aβ deposition.

BACKGROUND:The alteration of miR-146a-3p level is a common event in the pathogenesis of most neurological diseases,and the specific mechanism of miR-146a-3p regulation of astrocytes has not been studied. OBJECTIVE:To verify that miR-146a-3p regulates astrocyte proliferation,migration and apoptosis through insulin-like growth factor 1. METHODS:12 SD rats were divided into a sham operation group and a spinal cord injury group,with six rats in each group.RNA sequencing analysis was performed on the spinal cord tissues of all groups 2 weeks after surgery to screen out the differential genes(log2FC>2),and to select spinal cord injury-related genes(Score>20)in the Genecards database,and then to predict the target genes of miR-146a-3p by Targetscan.The intersection of three gene sets was obtained to screen out insulin-like growth factor 1 as one of the important target genes.qPCR,western blot assay and immunohistochemistry were performed to analyze the expression level of insulin-like growth factor 1 in spinal cord tissues.The primary astrocytes were divided into NC group,NC-mimics group and miR-146a-3p mimics group.Annexin-V/PI staining was used to detect cell apoptosis.CCK-8 assay was used to detect cell proliferation.Transwell assay was used to detect cell migration ability. RESULTS AND CONCLUSION:The expression of miR-146a-3p in the spinal cord tissue of the spinal cord injury group was lower than that of the sham operation group(P<0.05).The expression of insulin-like growth factor 1 in the spinal cord tissue of the spinal cord injury group was higher than that of the sham operation group(P<0.05).Compared with the NC group and NC-mimics group,the apoptotic rate of astrocytes was increased(P<0.01);the proliferation of astrocytes was decreased(P<0.01)and the number of migration was decreased(P<0.01)in the miR-146a-3p mimics group.To conclude,the expression of miR-146a-3p decreased and the expression of insulin-like growth factor 1 increased in spinal cord tissue after spinal cord injury.miR-146a-3p targeted regulation of insulin-like growth factor 1 in astrocytes,inhibited the proliferation and migration of astrocytes and promoted their apoptosis.

Objective To explore the effect of multi-sensory artificial intelligence feedback gait training on the recovery of walking function in stroke patients based on enriched environment theory. Methods From July,2021 to June,2023,a total of 80 stroke patients in Huashan Hospital Affiliated to Fudan University were randomly divided into control group(n=40)and experimental group(n=40).Both groups received rou-tine rehabilitation in the lying and seated positions,for 40 minutes.The control group received ground walking training,for 20 minutes,while the experimental group received multi-sensory feedback gait training in enriched environment,for 20 minutes.Before and after four weeks intervention,the digital motion monitoring treadmill was used to mearsure step speed,step length,hip and knee swing angle and weight symmetry.They were as-sessed with Berg Balance scale(BBS),Fugl-Meyer Assessment-Lower Extremities(FMA-LE)and Barthel Index(BI). Results After intervention,the hip swing angle,step length of both sides and step speed significantly improved in both groups(|t|＞3.162,P＜0.05),and they were better in the experimental group than in the control group(|t|＞2.568,P＜0.05);the average knee joint swing angle and bilateral weight-bearing symmetry significantly im-proved in the experimental group(|t|＞3.249,P＜0.01);the scores of BBS,FMA-LE and BI improved in both groups(|t|＞3.569,P＜0.01),and they were better in the experimental group than in the control group(|t|＞2.922,P＜0.05). Conclusion Multi-sensory feedback gait training based on enriched environment theory could effectively improve the walking and balance of stroke patients,and increase the ability of independence.

Objective:To explore the association of human betaine-homocysteine methyltransferase ( BHMT) and BHMT2 gene polymorphisms with non-syndromic congenital heart disease (CHD). Methods:A hospital-based case-control study was conducted, in which children with CHD who attended Hunan Children′s Hospital from January 2018 to May 2019 were enrolled as the case group, and children without any congenital deformity who attended the hospital during the same period were enrolled as the control group on a 1∶1 basis. A self-administered questionnaire survey was performed to collect information about the study subjects and their mothers, and then venous blood samples were collected from the subjects to detect BHMT and BHMT2 gene polymorphisms. Logistic regression analyses were used to evaluate the association of BHMT and BHMT2 gene polymorphisms and their haplotypes with CHD. Crossover analyses and logistic regression were used to explore the gene-gene and gene-environment interactions. Results:The case and control group both enrolled 620 children. The multivariate logistic regression showed that BHMT gene polymorphisms at rs3733890 (AA vs. GG: OR=3.476, Q FDR<0.001; GA vs. GG: OR=1.525, Q FDR=0.036), at rs1915706 (CC vs. TT: OR=3.464, Q FDR<0.001) and at rs1316753 (GG vs. CC: OR=1.875, Q FDR=0.020) increased the risk of CHD. Children with haplotype of A-G-A had an increased risk of CHD ( OR=1.468, 95% CI: 1.222-1.762). Interaction analysis showed that a statistically significant positive interaction between rs3733890 and rs1915706 on both additive ( RERI=0.628, 95% CI: 0.298-0.958) and multiplicative ( OR=3.754, 95% CI: 1.875-7.519) scales. Gene-environment interactions were found between the BHMT gene with secondhand smoke exposure before pregnancy and in early pregnancy, tea consumption before pregnancy and in early pregnancy, alcohol consumption before pregnancy, and folic acid supplementation before or during pregnancy. Conclusion:BHMT gene rs3733890, rs1915706 and rs1316753 polymorphisms may be associated with the risk of CHD. In addition, there is an association of cooperative interaction between rs3733890 and rs1915706 on both additive and multiplicative scales with the risk of CHD, and the BHMT gene interacts with multiple environmental factors.

Diabetic retinal neurodegeneration is a serious complication of diabetes mellitus, manifested by apoptosis and gliosis, and its pathogenesis is closely related to the oxidative stress induced by high glucose levels. The increase in blood glucose in the body leads to excessive production of reactive oxygen species and the downregulation of antioxidant defense signaling pathways, which leads to oxidative stress in the body, which in turn induces apoptosis, mitochondrial damage and autophagy, resulting in diabetic retinal neurodegeneration. Antioxidant stress therapy with gene therapy, flavonoids, recombinant Ad-β-catenin carriers, and autophagy inducers to exert neuroprotective effects. In the future, more clinical trials are needed to explore the effective dosage and side effects of drugs, and to develop new drugs and treatment strategies for oxidative stress to prevent and treat diabetic retinal neurodegeneration and protect retinal nerve function.

Objective:To explore the association of human betaine-homocysteine methyltransferase ( BHMT) and BHMT2 gene polymorphisms with non-syndromic congenital heart disease (CHD). Methods:A hospital-based case-control study was conducted, in which children with CHD who attended Hunan Children′s Hospital from January 2018 to May 2019 were enrolled as the case group, and children without any congenital deformity who attended the hospital during the same period were enrolled as the control group on a 1∶1 basis. A self-administered questionnaire survey was performed to collect information about the study subjects and their mothers, and then venous blood samples were collected from the subjects to detect BHMT and BHMT2 gene polymorphisms. Logistic regression analyses were used to evaluate the association of BHMT and BHMT2 gene polymorphisms and their haplotypes with CHD. Crossover analyses and logistic regression were used to explore the gene-gene and gene-environment interactions. Results:The case and control group both enrolled 620 children. The multivariate logistic regression showed that BHMT gene polymorphisms at rs3733890 (AA vs. GG: OR=3.476, Q FDR<0.001; GA vs. GG: OR=1.525, Q FDR=0.036), at rs1915706 (CC vs. TT: OR=3.464, Q FDR<0.001) and at rs1316753 (GG vs. CC: OR=1.875, Q FDR=0.020) increased the risk of CHD. Children with haplotype of A-G-A had an increased risk of CHD ( OR=1.468, 95% CI: 1.222-1.762). Interaction analysis showed that a statistically significant positive interaction between rs3733890 and rs1915706 on both additive ( RERI=0.628, 95% CI: 0.298-0.958) and multiplicative ( OR=3.754, 95% CI: 1.875-7.519) scales. Gene-environment interactions were found between the BHMT gene with secondhand smoke exposure before pregnancy and in early pregnancy, tea consumption before pregnancy and in early pregnancy, alcohol consumption before pregnancy, and folic acid supplementation before or during pregnancy. Conclusion:BHMT gene rs3733890, rs1915706 and rs1316753 polymorphisms may be associated with the risk of CHD. In addition, there is an association of cooperative interaction between rs3733890 and rs1915706 on both additive and multiplicative scales with the risk of CHD, and the BHMT gene interacts with multiple environmental factors.

BACKGROUND: Lung cancer is a disease with a high incidence rate in Yunnan province, yet there is a paucity of large-scale studies on its clinical epidemiology. This research aims to investigate the epidemiological characteristics of patients who underwent lung cancer surgery at Yunnan Cancer Hospital over the past decade, thereby providing a theoretical basis for the prevention and treatment of lung cancer. METHODS: Clinical data were collected from 15,967 patients who underwent lung cancer surgery at Yunnan Cancer Hospital between 2013 and 2022. A statistical analysis was conducted on the patients' general data, surgical information, pathological types of lung cancer, and other clinical epidemiological characteristics. RESULTS: Among the 15,967 cases of lung cancer, 46.3% were male and 53.7% were female, with the male-to-female ratio ranging from 0.68 to 1.61:1. The median age was 56 years (interquartile range: 49-63), and 37.0% of the patients were in the age group of 50-59 years. Since 2017, there has been an annual increase in the proportion of patients under the age of 60 years. The smoking status of the patients showed that 28.1% were smokers and 71.9% were non-smokers. Qujing city accounted for 41.4% and Kunming city for 23.2% of the cases in Yunnan province, with 29.6% of patients originating from Xuanwei and Fuyuan areas of Qujing city. The distribution of affected lung lobes was as follows: right upper lobe 28.2%, right middle lobe 6.3%, right lower lobe 20.1%, left upper lobe 22.7%, and left lower lobe 16.4%. The use of thoracoscopic surgery increased from 30.8% to 96.3%, with single-port thoracoscopic surgery comprising 61.3%. Lobectomy was performed in 64.2% of cases, wedge resection in 17.2%, and segmentectomy in 12.2%. The proportion of lobectomy decreased from 83.1% to 46.1%. The proportion of patients in stages 0-I increased from 43.5% to 82.8%, while stages II-IV decreased from 56.5% to 17.2%. Adenocarcinoma increased from 75.6% to 88.3%, and squamous cell carcinoma decreased from 21.5% to 8.6%. Among adenocarcinoma patients, 60.9% were female. Among sguamous cell carcinoma patients, 90.6% were male. The peak age for adenocarcinoma was 50-59 years, and for squamous cell carcinoma, it was 60-69 years. The smoking rate was higher among squamous cell carcinoma patients (65.9%) compared to adenocarcinoma patients (22.3%). Adenocarcinoma patients had a higher proportion in stages 0-I (76.3%), while squamous cell carcinoma patients were more prevalent in stages II-III (64.1%). CONCLUSIONS The findings indicate an increasing proportion of female patients with adenocarcinoma, a younger age of onset, a higher proportion of non-smoking lung cancer patients, and an increased proportion of stages 0-I lung cancer. These trends may reflect the epidemiological characteristics of patients undergoing lung cancer surgery in Yunnan and surrounding areas over the past decade.
Humans ; Female ; Male ; Lung Neoplasms/pathology* ; Middle Aged ; China/epidemiology* ; Aged ; Adult ; Aged, 80 and over

High glucose level, bacterial infection, and persistent inflammation within the microenvironment are key factors contributing to the delay of diabetic ulcers healing, while traditional therapeutic methods generally fail to address these issues simultaneously. Here, we present a spatiotemporally responsive cascade bilayer microneedle (MN) patch for accelerating diabetic wound healing via local glucose depletion and sustained nitric oxide (NO) release for long-term antibacterial and anti-inflammatory effects. The MN patch (G/AZ-MNs) possesses a degradable tip layer loading glucose oxidase (GOx), as well as a dissolvable base layer encapsulating l-arginine (Arg)-loaded nanoparticles (NPs). After wound administration, the base part rapidly dissolved, resulting in prompt separation of the MN tip within the wound tissue, which subsequently responded to the overexpressed matrix metalloproteinase-9 (MMP-9) in diabetic lesions, leading to the responsive release of GOx. The released enzyme catalyzed glucose into gluconic acid and hydrogen peroxide (H₂O₂), which not only reduced glucose level within the diabetic wound, but also initiated the cascade reaction between H₂O₂ with the Arg that was released from NPs, thereby achieving continuous production of NO for 7 days. Our findings demonstrate that a single administration of the MN patch could effectively heal non-infected or biofilm-infected diabetic wounds with the multifunctional properties.