BACKGROUND:Studies have shown that metformin has anti-inflammatory,anti-tumor,anti-aging and vasoprotective effects,and can inhibit the progression of osteoarthritis,but its specific mechanism of action remains unclear. OBJECTIVE:To investigate the mechanism of metformin on cartilage protection in a rat model of osteoarthritis. METHODS:Forty male Sprague-Dawley rats were randomly divided into four groups(n=10 per group):blank,control,sham-operated,and metformin groups.The blank group did not undergo any surgery.In the sham-operated group,the joint cavity was exposed.In the model group and the metformin group,the modified Hulth method was used to establish the osteoarthritis model.At 1 day after modeling,the rats in the metformin group were given 200 mg/kg/d metformin by gavage,and the model,blank,and sham-operated groups were given normal saline by gavage.Administration in each group was given for 4 weeks consecutively.Hematoxylin-eosin staining,toluidine blue staining,and safranin O-fast green staining were used to observe the morphological structure of rat knee joints.Immunohistochemical staining and western blot were used to detect the protein expression of SOX9,type Ⅱ collagen,a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),Beclin1,P62,phosphatidylinositol 3-kinase(PI3K),p-PI3K,protein kinase B(AKT),p-AKT,mammalian target of rapamycin(Mtor),and p-Mtor in rat cartilage tissue. RESULTS AND CONCLUSION:The results of hematoxylin-eosin,toluidine blue and safranin O-fast green staining showed smooth cartilage surface of the knee joints and normal histomorphology in the blank group and the sham-operated group,while in the model group,there was irregular cartilage surface of the knee joint and cartilage damage,with a decrease in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.In the metformin group,there was a significant improvement in the damage to the structure of the cartilage in the knee joints of the rats,and the cartilage surface tended to be smooth,with an increase in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.Immunohistochemistry staining and western blot results showed that compared with the control and sham-operated groups,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the model group was significantly decreased(P<0.05).Conversely,the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly increased(P<0.05).Furthermore,compared with the model group,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the metformin group was significantly increased(P<0.05),while the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly decreased(P<0.05).To conclude,Metformin can improve the autophagy activity of chondrocytes and reduce the degradation of cartilage matrix in osteoarthritis rats by inhibiting the activation of PI3K/AKT/Mtor signaling pathway,thus exerting a protective effect on articular cartilage.

Liver fibrosis is the intermediate stage in the progression of many chronic liver diseases to liver cirrhosis， and although there is still a lack of widely accepted and effective chemical or biological agents for reversing liver fibrosis， significant progress has been made in the treatment of liver fibrosis with traditional Chinese medicine. This article elaborates on the molecular mechanisms of different herbal extracts， a single Chinese herb， and Chinese patent drugs in reversing liver fibrosis， such as inhibiting liver inflammation， exerting an effect on lipid peroxidation damage， inhibiting the activation and proliferation of hepatic stellate cells， regulating the synthesis and secretion of pro-fibrogenic factors， and regulating the synthesis and degradation of extracellular matrix， in order to provide more precise options for the treatment of liver fibrosis in the future.

BACKGROUND: Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China. METHODS: We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model. RESULTS: From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%). CONCLUSIONS CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.
Humans ; Heart Defects, Congenital/mortality* ; Male ; Female ; China/epidemiology* ; Infant ; Child, Preschool ; Adult ; Child ; Adolescent ; Infant, Newborn ; Middle Aged ; Young Adult ; Aged ; Rural Population

OBJECTIVE To explore the distribution pattern of traditional Chinese medicine(TCM)syndrome types of primary o-varian insufficiency(POI)sleep disorders and the differences in the distribution of sleep quality index among different syndrome types,in order to provide a basis for syndrome differentiation treatment and prevention of POI associated with sleep disorders.METHODS 600 POI patients who met the inclusion criteria were collected for epidemiological investigation,and 405 patients who met the diagnosis of sleep disorders were selected as the research group.The patients'general information,TCM four diagnosis and sex hormone level in-formation were collected,and the Pittsburgh sleep quality index(PSQI)scale was used to evaluate patients'sleep conditions,and ana-lyze the characteristics and influencing factors of TCM syndrome types of POI associated with sleep disorders.RESULTS The main TCM syndrome types of POI accompanied by sleep disorders were heart and kidney disharmony syndrome(41.98%),spleen and kid-ney yang deficiency syndrome(22.22%),kidney deficiency and liver stagnation syndrome(20.99%),and kidney deficiency and blood stasis syndrome(14.81%).The heart and kidney disharmony syndrome had the longest sleep latency and shortest sleep time,relied more on hypnotic drugs,and had the highest PSQI total score;the heart and kidney disharmony syndrome and kidney deficiency and liver stagnation syndrome had the worst sleep quality;the spleen kidney yang deficiency syndrome had the highest daytime dysfunc-tion score.There was no significant difference in FSH levels among different TCM syndrome types;the distribution of E2 values from low to high was:heart and kidney disharmony syndrome,kidney deficiency and liver stagnation syndrome,spleen and kidney yang de-ficiency syndrome,and kidney deficiency and blood stasis syndrome,and there were significant differences among multiple groups(P<0.05).CONCLUSION The main TCM syndrome types of patients with POI and sleep disorders are heart and kidney disharmony syn-drome,spleen and kidney yang deficiency syndrome,kidney deficiency and liver stagnation syndrome,and kidney deficiency and blood stasis syndrome.Among them,the most common TCM syndrome type with the worst sleep quality is heart and kidney disharmony syn-drome,which may be closely related to estrogen E2 levels.

Objective:Insulin resistance(IR)is closely associated with atherosclerosis and adverse cardiovascular events.The triglyceride-glucose(TyG)index is an effective indicator for assessing IR.This study aims to explore the relationship between the TyG index and the risk of arterial stiffness progression. Methods:This retrospective cohort study included adults who had undergone at least 2 health examinations with arteriosclerosis testing at the Health Management Medical Center of the Third Xiangya Hospital,Central South University,between January 2012 and December 2022.Clinical data were collected.The TyG index was calculated using the formula of ln(triglyceridesxfasting blood glucose/2).The baseline TyG index was assessed as both a continuous variable and as a quartile-based categorical variable.The progression of arteriosclerosis was evaluated by the annual change rate of brachial-ankle pulse wave velocity(baPWV)and the new onset of increased arterial stiffness.Linear regression model and Cox proportional hazard model were used to explore whether the TyG index is an independent risk factor for arterial stiffness progression.Subgroup analyses were performed based on age,gender,body mass index(BMI),and the presence of type 2 diabetes,hypertension,or hyperlipidemia to determine the characteristics of the association between the TyG index and arterial stiffness progression. Results:A total of 4 971 participants were included,with a follow-up period of(3.01±1.98)years.During follow-up,the annual baPWV change rate was(24.94±81.15)cm/s,and 278 cases of new onset of increased aterial stiffness were recorded.After fully adjusting for confounding factors,the baseline TyG index was independently positively correlated with both the annual baPWV change rate(β=17.5,95％CI 9.00 to 25.94,P＜0.001)and the risk of new onset of increased aterial stiffness[hazard ratio(HR)=1.43,95％CI 1.18 to 1.74,P＜0.001]when the TyG index was treated as a continuous variable.When treated as a categorical variable,higher TyG index quartiles were associated with progressively higher baPWV change rates and new onset of increased arterial stiffness(all P＜0.055).In subgroups of participants aged ≥45 years,males,BMI＜28 kg/m2,those with or without hypertension,and those without type 2 diabetes or hyperlipidemia,the baseline TyG index(both continuous and categorical)was significantly associated with new onset of increased arterial stiffness(all P＜0.05),with no significant interactions observed across subgroups(all P＞0.05). Conclusion:The TyG index is independently associated with an increased risk of arterial stiffness progression and may serve as a useful indicator for assessing arterial stiffness progression risk in health check-up populations.

Objective To investigate the effects of icariin on high glucose-induced autophagy and apoptosis of podocytes,and the regulating effects on mammalian target of rapamycin(mTOR)/serine-threonine kinase(Akt)/cyclic adenosine monophosphate response element binding protein(CREB)pathway.Methods The mouse podocytes MPC5 were taken and divided into five groups:normal control group(5.5 mmol·L-1 glucose),high glucose group(30 mmol·L-1 glucose),icariin group(30 mmol·L-1glucose+5 μmol·L-1icariin),GDC-0349 group(30 mmol·L-1glucose+50 μmol·L-1 GDC-0349),icariin+GDC-0349 group(30 mmol·L-1 glucose+5 μmol·L-1 icariin+50 μmol·L-1 GDC-0349).Cultured for 48 hours,the tetramethylazozolium salt method was used to detect the viability of MPC5 cells;acridine orange staining was used to observe the autophagy of MPC5 cells;apoptosis of MPC5 cells was detected by flow cytometry;Western blotting was used to detect the expression of autophagy[microtubule associated protein one light chain 3(LC3)II,LC3Ⅰ,autophagy-related protein(Beclin-1)],apoptosis[Bcl-2 related X protein(Bax),B cell lymphoma-2(Bcl-2)]and mTOR/Akt/CREB pathway-related proteins of MPC5 cells.Results Compared with the normal control group,the cell viability,expression levels of Bcl-2,phosphorylated mTOR(p-mTOR)/mTOR,phosphorylated Akt(p-Akt)/Akt,phosphorylated CREB(p-CREB)/CREB protein of MPC5 cells in the high glucose group were significantly decreased(P＜0.05),the autophagy ability was enhanced,the autophagosome showed orange fluorescence,and the apoptosis rate,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bax protein expression levels were significantly increased(P＜0.05).Compared with the high glucose group,the cell viability,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bcl-2,p-mTOR/mTOR,p-Akt/Akt,p-CREB/CREB protein expression levels of MPC5 cells in icariin group were significantly increased,the autophagy ability was further enhanced,the number of autophagosomes was increased,the autophagosomes showed brick red fluorescence(P＜0.05),the apoptosis rate and Bax protein expression level were significantly decreased(P＜0.05),and the cell viability,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bcl-2,p-mTOR/mTOR,p-Akt/Akt and p-CREB/CREB proteins expression levels of MPC5 cells in GDC-0349 group were significantly decreased,the autophagy ability was weakened,the number of autophagosomes was reduced,the autophagosomes showed orange fluorescence(P＜0.05),and the apoptosis rate and Bax protein expression level were significantly increased(P＜0.05);icariin+GDC-0349 could reverse the effect of icariin on high glucose induced MPC5 cells(P＜0.05).Conclusion Icariin promotes elevated glucose-induced podocyte autophagy and inhibits apoptosis by activating the mTOR/Akt/CREB pathway.

Objective: To compare the efficacy of two bioceramic materials, iRoot BP Plus and mineral trioxide aggregate (MTA) in the preservation of vital pulp of mature permanent teeth with exposed pulp of caries origin, so as to provide insights into appropriate selection of pulp capping agents in clinical process. Methods: Vital pulp therapy were performed on 120 mature permanent teeth with carious exposure at the Department of Stomatology of Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University. The teeth were randomly divided into two groups which were treated respectively by iRoot BP Plus (iRoot group) and MTA (MTA group). The clinical efficacy was evaluated by clinical examinations and imaging examinations. Results: There were 60 cases in iRoot group, including 23 males and 37 females, 27 cases affected premolars and 33 cases affected molars, and 8 cases of Class I and 52 cases of Class II cavity type, with a median age of 41 (interquartile range, 12) years. There were 60 cases in MTA group, including 29 males and 31 females, 21 cases affected premolars and 39 cases affected molars, and 10 cases of Class I and 50 cases of Class II cavity type, with a median age of 39 (interquartile range, 14) years. There were no significant differences in gender, age, affected tooth location and cavity type between the two groups (P>0.05). The success rate of iRoot group at 12 months was 91.67% while the MTA group was 88.33%, and the pulp infection rate of iRoot group at 12 months was 8.33% while the MTA group was 11.67%. There were no significant differences in success rate and pulp infection rate between the two groups (P>0.05). The rate of crown discoloration in MTA group was 61.67%, while there was no discoloration in iRoot group. Conclusions During 12 months, iRoot BP Plus and MTA can both achieve great effects in the treatment of mature permanent teeth with carious pulp exposure, but there is a problem of tooth discoloration after pulp covering using MTA. The long-term clinical effects of the two materials need to be further studied.

Objective:To study and screen the differential expression of inflammatory proteins in diabetes skin ulcers and common skin ulcers, so as to provide experimental basis for further research on anti-inflammatory and healing drug targets of diabetes skin ulcers.Methods:The tissues of 11 patients with diabetes skin ulcer, 12 patients with common skin ulcer and 11 patients with normal skin were collected from the First Hospital of Hunan University of Chinese Medicine. The levels of inflammatory protein Toll like receptor 4 (TLR4), nuclear factor κB (NF-κB), pro-inflammatory factor interferon -γ (IFN -γ), tumor necrosis factor - α (TNF -α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1β (IL-1β), macrophage chemotactic protein-1 (MCP-1), anti-inflammatory factors epidermal growth factor (EGF), interleukin-4 (IL-4), and interleukin-10 (IL-10) were detected in three groups of tissues using enzyme-linked immunosorbent assay (ELISA).Results:Compared with normal tissues, the concentrations of TLR4, NF-κB, IFN -γ, TNF -α, IL-1β, IL-6, IL-8, MCP-1 and EGF in common ulcer skin tissues and diabetes ulcer tissues were higher, and the concentrations of IL-10 were lower, with statistically significant differences (all P<0.05); Compared with the normal tissue, the concentration of IL-4 in diabetes ulcer tissue was lower, the difference was statistically significant ( P<0.05); Compared with ordinary ulcer skin tissue, the concentrations of TLR4, NF-κB and MCP-1 in diabetes ulcer tissue were higher, and the concentrations of IL-4 were lower, with statistically significant differences (all P<0.05). Conclusions:The skin ulcer in diabetes patients will have inflammatory reaction, and high glucose promotes the inflammatory reaction of skin ulcer, which may be related to the abnormal expression of TLR4, NF-κB, MCP-1 and IL-4. TLR4/NF-κB signal pathway and inflammatory factors MCP-1 and IL-4 may be the target of the inflammation regulation of diabetes skin ulcer.

Objective To explore the relationship between geriatric nutritional risk index(GNRI)and adverse outcomes in elderly patients undergoing maintenance hemodialysis(MHD).Methods A prospective cohort trial was conducted on 337 MHD patients aged ≥60 years in hemodialysis centers of 11 hospitals in Beijing from April to June 2017.Their baseline data were collected,and they were divided into non-malnutrition(GNRI≥98,226 cases),mild malnutrition(92≤GNRI＜98,81 cases),and major malnutrition groups(GNRI＜92,30 cases).All of them were followed up until June 2018.The endpoint events were all-cause mortality and cardiovascular disease(CVD)mortality.Kaplan-Meier survival analysis was used to compare the cumulative survival rate among the 3 groups.Multivariate Cox regression model was employed to analyze the relationship of GNRI with all-cause and CVD mortality.Results The mild and major malnutrition groups had significantly lower BMI,serum albumin level and GNRI(P＜0.01).During the median follow-up of 52(4.4-52.0)weeks,56(16.6％)patients died of all-cause death and 25(44.6％)of CVD death.Kaplan-Meier survival curve showed significant differences in all-cause mortality(x2=30.484,P＜0.01)and CVD mortality(x2=22.398,P＜0.01)in the 3 groups.Multivariate Cox regression analysis indicated that,as a continuous variable,elevated GNRI was a protective factor for all-cause mortality(HR=0.910,95％CI:0.870-0.952,P=0.000)and CVD mortality(HR=0.895,95％CI:0.852-0.940,P=0.000),and as a categorical variable,mild and major malnutri-tion were independently correlated with all-cause and CVD mortality(P＜0.05).Conclusion GNRI is an independent risk factor for all-cause and CVD mortality in elderly MHD patients.Mo-nitoring the nutritional status using GNRI can predict the risk of adverse prognosis.

Objective:To explore the early predictive value of umbilical cord blood S100β protein and lactate combined with amplitude integrated electroencephalogram（aEEG）in small for gestational age（SGA）preterm infants with brain injury.Methods:One hundred and six cases of SGA preterm infants were enrolled in this study in Neonatology Department of Inner Mongolia People's Hospital from January 2019 to December 2021. Umbilical cord blood serum S100β protein and lactate at birth of All SGA preterm infants were tested，and aEEG was monitored at 6h and 72 h after birth，corrected gestational age of 32 weeks and 37 weeks. According to the diagnostic criteria of brain injury in preterm infants，SGA preterm infants were divided into brain injury group（45 cases）and non-brain injury group（61 cases），and compared the differences of S100β protein，lactate and the designated time aEEG between the two groups.SGA preterm infants with brain injury were further divided into symmetrical group（28 cases）and non-symmetrical group（15 cases）. The differences of umbilical cord blood S100β protein and lactate level between the two groups were compared，and the diagnostic value in different types of SGA preterm infants with brain injury was also compared.Results:SGA preterm infants in the brain injury group had significantly higher levels of umbilical cord blood S100β protein［（0.826±0.218）μg/L vs（0.397±0.196）μg/L， t=8.316， P<0.05］and lactate［（8.5±1.3）mmol/L vs（3.8±0.9）mmol/L， t=3.281， P<0.05］than those in non-brain injury group.Symmetric SGA group had higher level of S100β protein than the asymmetric SGA group［（0.924±0.205）μg/L vs（0.438±0.196）μg/L， t=5.734， P<0.05］.But there was no statistically significant difference in lactate levels［（5.6±1.4）mmol/L vs（3.9±1.2）mmol/L， t=0.932， P>0.05］between symmetric SGA group and asymmetric SGA group. The abnormal rates of aEEG in brain injury group and non-brain injury group were respectively 100%（45/45）vs 22.95%（14/61）at 6 h after birth，95.56%（43/45）vs 16.39%（10/61）at 72 h after birth，62.22%（28/45）vs 6.56%（4/61）at 32 weeks of corrected gestational age，22.22%（10/45）vs 3.28%（2/61）at 37 weeks of corrected gestational age. The abnormal rate of brain injury group was higher than the non-brain injury group in the same nodal time，and the differences were statistically significant（ χ 2 value respectively 62.292，64.913，38.074，9.257，all P<0.05）. Conclusion:There were significant value in umbilical cord blood S100β protein，lactate level and aEEG monitoring in the early diagnosis in preterm infants SGA with brain injury. The combination of the three might be more helpful for the early diagnosis and timely treatment of brain injury in SGA preterm infants.