ObjectiveTo explore the underlying mechanism by which the Chinese medicine compound Yitangkang granule（YTK） treats diabetic kidney disease （DKD） by observing its effects on podocyte autophagy through the regulation of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead transcription factor O1 （FoxO1） signaling pathway mediated by silent information regulator 1 （SIRT1） via advanced glycation end products （AGE）/receptor for AGE （RAGE） axis. MethodNinety-six 8-week-old healthy male SPF-grade Wistar rats were selected and randomly divided into blank control group （B）， model control group， high-dose YTK （40 g·kg^-1）， medium-dose YTK （20 g·kg^-1）， low-dose YTK （10 g·kg^-1）， and Western medicine control （20 mg·kg^-1 losartan） groups. The DKD rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After successful modeling， the rats in each group received the corresponding treatments for eight weeks. The levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and catalase （CAT） were measured according to the instructions of the respective assay kits. Hematoxylin and eosin （HE） staining was used to observe pathological changes in kidney tissues. Immunohistochemistry was employed to detect the average optical density values of α-smooth muscle actin （α-SMA）， fibronectin （FN）， desmin， and nephrin. Western blot analysis was used to measure the expression levels of PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， RAGE， SIRT1， Caspase-3， and FoxO1 proteins in kidney tissues of DKD rats. ResultCompared with the blank control group， the model group showed significantly lower levels of SOD， GSH-Px， and CAT， and significantly higher levels of MDA （P<0.01）. The rats exhibited severe kidney damage. The positive expression of podocyte marker proteins α-SMA， FN， and desmin increased significantly， while nephrin and podocin significantly decreased （P<0.01）. The expression levels of PI3K， p-PI3K， Akt， p-Akt， RAGE， and Caspase-3 proteins were significantly elevated， while SIRT1 and FoxO1 protein levels were significantly reduced （P<0.01）. Compared with the model control group， rats in the YTK treatment groups showed significantly higher levels of SOD， GSH-Px， and CAT， and significantly lower levels of MDA in serum （P<0.01）. The degree of kidney damage was reduced to varying extents. The average optical density values of podocyte marker proteins α-SMA， FN， and desmin were significantly decreased， while nephrin and podocin significantly increased （P<0.01）. The expression levels of PI3K， p-PI3K， Akt， p-Akt， RAGE， and Caspase-3 in kidney tissues were significantly reduced， while SIRT1 and FoxO1 expression levels significantly increased （P<0.01）. The Chinese medicine groups demonstrated a clear dose-response trend. ConclusionYTK may alleviate kidney pathological damage， reduce proteinuria， and protect kidney function in DKD rats， thereby delaying the progression of DKD by improving podocyte autophagy through the AGE-RAGE axis-mediated SIRT1 regulation of the PI3K/Akt/FoxO1 signaling pathway. Additionally， a dose-response relationship was observed in the Chinese medicine groups.

In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

Background::Prenatal and postnatal factors may have joint effects on cardiovascular health, and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics (ICVHMs) prospectively in adulthood with incident cardiovascular disease (CVD).Methods::In the UK Biobank, 227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women.Results::Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared with participants with birth weights of 2.5-4.0 kg, the HRs (95% CIs) of CVD among those with low birth weights was 1.08 (1.00-1.16) in men and 1.23 (1.16-1.31) in women. The association between having a birth weight <2.5 kg and CVD risk in men was more prominent for those aged <50 years than for those of older age ( P for interaction = 0.026). Lower birth weight and non-ideal cardiovascular health metrics were jointly related to an increased risk of CVD. Participants with birth weights <2.5 kg and ICVHMs score 0-1 had the highest risk of incident CVD (HR [95% CI]: 3.93 [3.01-5.13] in men; 4.24 [3.33-5.40] in women). The joint effect (HR [95% CI]: 1.36 [1.17-1.58]) could be decomposed into 24.7% (95% CI: 15.0%-34.4%) for a lower birth weight, 64.7% (95% CI: 56.7%-72.6%) for a lower ICVHM score, and 10.6% (95% CI: 2.7%-18.6%) for their additive interaction in women. Conclusions::Birth weight and ICVHMs were jointly related to CVD risk. Attaining a normal birth weight and ideal ICVHMs may reduce the risk of CVD, and a simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases in women.

Background::Life’s Simple 7, the former construct of cardiovascular health (CVH) has been used to evaluate adverse non-communicable chronic diseases (NCDs). However, some flaws have been recognized in recent years and Life’s Essential 8 has been established. In this study, we aimed to analyze the association between CVH defined by Life’s Essential 8 and risk of 44 common NCDs and further estimate the population attributable fractions (PAFs) of low-moderate CVH scores in the 44 NCDs.Methods::In the UK Biobank, 170,726 participants free of 44 common NCDs at baseline were included. The Life’s Essential 8 composite measure consists of four health behaviours (diet, physical activity, nicotine exposure, and sleep) and four health factors (body mass index, non-high density lipoprotein cholesterol, blood glucose, and blood pressure), and the maximum CVH score was 100 points. CVH score was categorized into low, moderate, and high groups. Participants were followed up for 44 NCDs diagnosis across 10 human system disorders according to the International Classification of Diseases 10th edition (ICD-10) code using linkage to national health records until 2022. Cox proportional hazard models were used in this study. The hazard ratios (HRs) and PAFs of 44 NCDs associated with CVH score were examined.Results::During the median follow-up of 10.85 years, 58, 889 incident NCD cases were documented. Significant linear dose-response associations were found between higher CVH score and lower risk of 25 (56.8%) of 44 NCDs. Low-moderate CVH (<80 points) score accounted for the largest proportion of incident cases in diabetes (PAF: 80.3%), followed by gout (59.6%), sleep disorder (55.6%), chronic liver disease (45.9%), chronic kidney disease (40.9%), ischemic heart disease (40.8%), chronic obstructive pulmonary disease (40.0%), endometrium cancer (35.8%), lung cancer (34.0%), and heart failure (34.0%) as the top 10. Among the eight modifiable factors, overweight/obesity explained the largest number of cases of incident NCDs in endocrine, nutritional, and metabolic diseases (35.4%), digestive system disorders (21.4%), mental and behavioral disorders (12.6%), and cancer (10.3%); however, the PAF of ideal sleep duration ranked first in nervous system (27.5%) and neuropsychiatric disorders (9.9%).Conclusions::Improving CVH score based on Life’s Essential 8 may lower risk of 25 common NCDs. Among CVH metrics, avoiding overweight/obesity may be especially important to prevent new cases of metabolic diseases, NCDs in digestive system, mental and behavioral disorders, and cancer.

ObjectiveTo investigate the material basis of homologous and heterogeneous effect of Aurantii Fructus Immaturus（AFI） and Aurantii Fructus（AF） based on the total statistical moment analysis and molecular connectivity index（MCI）. MethodRelevant literature at home and abroad and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） were consulted to establish the chemical composition database of AFI and AF， and set up their fingerprints by ultra-high performance liquid chromatography（UPLC）， and the total statistical moments and similarity parameters of the fingerprint were calculated. According to MCI， all components of AFI and AF were divided into different component groups， the average values of 0-8^th order（⁰χ-⁸χ） MCI of the common component groups of AFI and AF were calculated. ResultThe values of total zero-order moment（AUC_T） of AFI and AF were （10.57±2.45）×10⁶， （5.09±0.89）×10⁶ μV·s， the values of total first-order moment（MCRT_T） were （11.57±1.58）， （12.10±1.29） min， the values of total second-order moments（VCRT_T） were（24.49±2.30）， （26.49±2.54） min²， respectively. It showed that qualitative and quantitative parameters of AFI and AF were significantly different. The components with high similarity such as neohesperidin， hesperidin and narirutin were screened as the common potential pharmacodynamic components of AFI and AF. The non-common components of AFI， such as alysifolinone and imperatorin， and the non-common components of AF， such as neoeriocitrin and isosakuranin， with high similarity were screened out as potential heterogeneous components of AFI and AF. The composition groups of AFI and AF were classified into six categories， and the similarities between the composition groups of AFI and AF and the total constituents were 0.872-0.979 and 0.918-0.997， the average values of ⁰χ-⁸χ MCI of alkaloids in AFI and AF were 3.65 and 3.14， the average values of ⁰χ-⁸χ MCI of flavonoids were 8.47 and 8.47， the average values of ⁰χ-⁸χ MCI of volatile oils were 2.71 and 3.48， respectively. It showed that there were some differences in MCI of chemical constituents（groups） between AFI and AF. ConclusionThe chemical constituents（groups） of AFI and AF not only differ in content and species， but also in structural characteristics and structure-activity relationship， which can provide a basis for further explaining the scientific connotation of homologous and heterogeneous effect of AFI and AF.

Objective:To systematically review the medical decision-making for children with autism spectrum disorder (ASD) from the perspective of caregivers.Methods:It was a systematic review. Using search terms as “Autism”“loneliness disorder”“autism spectrum disorder”“parents”“caregiver”“medical decision making”, etc., qualitative studies on medical decision-making of ASD caregivers in the databases of PubMed, Web of Science, Cochrane Library, Embase, Scopus, CNKI.com, Wanfang Database, VIP database, and Chinese Biomedical Literature database were searched. The search was conducted from the inception of the databases to July 31, 2022, and the data was organized from August 1 to September 1, 2022. The literature quality was evaluated by two researchers according to the quality evaluation criteria for qualitative research at the Centre for Evidence-based Health Care, Joanna Briggs Institute, Australia. Pooled integration method was used to integrate the study results and evaluate the medical decision-making of children with ASD from the perspective of caregivers.Results:Seventeen studies were included, with two studies rated as quality grade A and fifteen studies rated as quality grade B. A total of 36 research findings were extracted. These findings were grouped into ten new categories based on similarities, which were further synthesized into three overarching results: the symptom-driven medical decision-making process, delays in medical decision-making due to individual, family, and societal factors, and the influence of personal experiences and multiple external pressures on medical decision-making.Conclusion:The factors that lead to the delay or promotion of medical decision of caregivers of children with ASD are complicated, and comprehensive intervention measures should be taken at individual, family and social levels to promote early medical diagnosis and intervention of the children with ASD.

Objective:To examine the structural network changes in participants with amnestic mild cognitive impairment(aMCI)and investigate the correlation between these changes and the onset of Alzheimer's disease(AD).Methods:In this prospective study, a total of 100 individuals with amnestic mild cognitive impairment(aMCI)were enrolled as the research group.Additionally, 25 healthy individuals who were matched in terms of age and sex were enrolled as healthy controls.Upon enrollment, all participants underwent MRI scans, neuropsychological assessments, and clinical evaluations.The participants were then followed every 6 months for a period of 36 months or until they withdrew from the study.Based on the outcome of the follow-up(whether Alzheimer's disease occurred), the aMCI participants were divided into two groups: stable aMCI group and progressive aMCI group.The Chinese version of the Brief Mental State Examination(MMSE), the Montreal Cognitive Assessment(MoCA), the Clinical Dementia Rating Scale(CDR), and the Auditory Word Learning Test(AVLT)were utilized to evaluate the overall mental and cognitive status of the subjects.Pearson correlation analysis was employed to investigate the relationship between structural network changes and cognitive decline.Logistic regression was performed to analyze the predictive ability of structural network changes in determining the onset of AD.Results:Compared to the stable aMCI group, the progressive aMCI group exhibited lower levels of global efficiency( P=0.002), local efficiency( P=0.007), feeder connections( P=0.003), local connections( P=0.008), and right precuneus nodal efficiency( P=0.010).Correlation analysis revealed that global efficiency( r=0.604, P=0.002), feeder connections( r=0.513, P=0.012), and right precuneus nodal efficiency( r=0.504, P=0.014)were correlated with AVLT-delay scores(baseline)in the progressive aMCI group.A logistic regression model demonstrated that global efficiency, feeder connections, and right precuneus nodal efficiency could significantly predict the onset of AD(all P<0.05, AUCunited=0.797, 95% CI: 0.684-0.884, sensitivity=73.91, 95% CI: 51.6-89.8, specificity=76.60, 95% CI: 62.0-87.7). Conclusions:Among participants with aMCI, individuals who exhibit lower global efficiency, feeder connections, or right precuneus nodal efficiency are at a higher risk of developing AD.These indicators are anticipated to serve as new targets for clinical intervention.

ObjectiveTo determine the mechanism of Yitangkang in correcting excessive apoptosis of skeletal muscle cells to improve insulin resistance （IR） by inhibiting the advanced glycation end product （AGE）/receptor for the advanced glycation end product （RAGE） signaling pathway. Method① In vitro experiments. Yitangkang-medicated serum was prepared. C2C12 cells were divided into a blank group， a model group， high-， medium-， and low-dose Yitangkang-medicated serum groups （40， 20， and 10 g·kg^-1）， and a RAGE inhibitor group. The IR model was induced by palmitic acid in C2C12 cells except for those in the blank group. After the corresponding intervention methods were conducted，the cell viability and glucose consumption level of each group were determined. In addition，the apoptosis rate was determined using flow cytometry. The mRNA and protein expression levels of the important apoptotic proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， p53， cysteinyl aspartate-specific protease-3 （Caspase-3）， and cysteinyl aspartate-specific protease-9 （Caspase-9）］ were determined using Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ② In vivo experiments. Ninety-six eligible Wistar rats were divided into a blank group， a model group， high-，medium-，and low-dose Yitangkang groups （40， 20， and 10 g·kg^-1）， and a western medicine group （pioglitazone hydrochloride，1.35 mg·kg^-1）. The IR model was induced using high-glucose and high-fat feed for diabetes combined with intraperitoneal injection of low-dose streptozotocin （STZ） in animals and verified by the hyperinsulinemic-euglycemic clamp （HEC） test. After the model was determined successfully， the rats in each group were given intragastric administration of drugs as required. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was performed to determine the number of positive apoptotic cells in the skeletal muscle tissues of rats in each group，while Real-time polymerase chain reaction（Real-time PCR） and Western blot were performed to determine the mRNA and protein expression levels of the important apoptotic proteins Bcl-2， Bax， p53， Caspase-3， and Caspase-9. Result① In vitro experiments. compared with the blank group， the model groups showed increased apoptosis rate of C2C12 cells and decreased cell viability and glucose consumption （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed decreased apoptosis rate of C2C12 cells and increased cell viability and glucose consumption （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in C2C12 cells and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed increased expression levels of Bcl-2 mRNA and protein in C2C12 cells （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. ② In vivo experiments. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the model group significantly increased as compared with that in the blank group （P<0.01）. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the Yitangkang groups and the western medicine group decreased as compared with that in the model group （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang groups and the western medicine group showed increased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. The medium-dose Yitangkang showed a similar effect as RAGE inhibitor， and the effect was equivalent to that of pioglitazone hydrochloride. ConclusionYitangkang can inhibit skeletal muscle cell apoptosis by inhibiting the AGE/RAGE signaling pathway.

Objective:To investigate the predictive values of serum fibroblast growth factor 22 (FGF22) levels and electrical P300 in depression patients occurred mild cognitive impairment (MCI).Methods:A prospective study was performed. A total of 94 depression patients without cognitive impairment admitted to our hospital from January 2020 to August 2021 were chosen. These patients were followed up for one year; Hamilton Depression Scale (HAMD)-24 items and Montreal Cognitive Assessment Scale (MoCA) were used to evaluate the neuropsychological function of the patients every 3 months; according to the occurrence of MCI, the patients were divided into depression with MCI group ( n=57), and depression without MCI group ( n=32). All patients underwent baseline P300 examination and baseline serum FGF22 levels were detected by enzyme-linked immunosorbent assay (ELISA), and the differences in clinical data, P300 examination results and serum FGF22 levels were compared between the two groups. Correlation analysis was performed to analyze the correlations of P300 latency and serum FGF22 level with MoCA scores. Multivariate Logistic regression analysis was used to screen the independent influence factors for MCI in patients with depression. The predictive value of P300 latency and serum FGF22 level in MCI in patients with depression was analyzed by receiver operating characteristic (ROC) curve. Results:As compared with the depression without MCI group, patients in the depression with MCI group had significantly lower years of education and serum FGF22 level, and significantly higher proportion of patients living alone, and statistically higher P300 latency ( P<0.05). The results of correlation analysis showed that the MoCA scores at MCI period were positively correlated with serum FGF22 level ( r=0.665, P<0.001) and negatively correlated with P300 latency ( r=-0.621, P<0.001) in patients from the depression with MCI group. Multivariate Logistic regression analysis showed that serum FGF22 level was a protective factor for MCI in patients with depression ( OR=0.805, 95%CI: 0.737-0.862, P=0.003), and P300 latency was a risk factor for MCI in patients with depression ( OR=1.136, 95%CI: 1.115-1.163, P=0.001). ROC curve analysis showed that the areas under the curve (AUC) of serum FGF22 level, P300 latency, serum FGF22 level combined with P300 latency in predicting MCI in depression patients were 0.779, 0.724, and 0.852, respectively. Conclusion:The abnormal serum FGF22 level and P300 latency are closely related to the occurrence of MCI in patients with depression, and the combination of the two can be used to predict the occurrence of MCI in patients with depression.

Objective:To investigate the clinicopathologic characteristics of hepatic echinococcus granulosus (HEG).Methods:Thirteen cases of HEG were collected from Linzhi People′s Hospital between January 2017 to October 2020, and their clinicopathologic features, ultrasound classi?cation, immunophenotype and histochemical data were analyzed, retrospectively and the relevant literature was reviewed.Results:Thirteen patients (5 male patients, 8 female patients) were included in this cohort, and the mean age was 40 years. The most common clinical presentation was mild abdominal distention and pain (9/13). Based on WHO-IWGE ultrasound standardized classi?cation, these cases were classified into 5 types, including type CL (1 case), type CE1 (2 cases), type CE2 (4 cases), type CE3 (3 cases) and type CE4 (3 cases). Gross examination revealed a solitary cyst localized in the liver, varying from 2.7 to 13.5 cm in diameter, and most of them(10/13)were more than 10 cm. Histopathologically, these cysts possessed a thin inner germinal layer and outer adventitial layer, and a central cavity ?lled with a clear"hydatid"?uid. The germinal layer was continuous and generated brood capsules and protoscoleces. The laminated membranes were clearly demonstrated by elastic fiber and Gomori′s stains. Inside the"mother"cyst, there were a varying number of"daughter"vesicles of variable sizes. The inflammatory reaction around the cyst consisted of eosinophils, mononuclear cells immediately next to the cyst layer and sometimes formed granuloma and giant cells resembling the Langhan′s type giant cells. The lymphoid cells were positive for CD20 and CD3. The CD68 immunohistochemistry clearly demonstrated epithelioid cells of granuloma in two cases. Moreover, immunohistochemistry revealed plasma cells were locally positive for CD38, IgG and IgG4, but not meeting the criteria for IgG4 related lesion.Conclusions:Hepatic echinococcus granulosus is a zoonotic parasitic disease prevalent in pastoral areas such as Tibet. It is important to understand its clinical features, ultrasound characteristics and histological morphology.