Objective: This study aimed to elucidate the mechanisms underlying the impaired bone healing capacity in type 1 diabetes (T1DM) by investigating the role of the Hedgehog (Hh) signaling pathway in the impaired healing of cranial defects caused by T1DM. Methods: This study was approved by the experimental animal ethics committee of our hospital. A cranial defect model was established using Akita transgenic mice with spontaneous type I diabetes. The impact of T1DM on osteogenic differentiation and the Hh signaling pathway during cranial defect healing was explored by MicroCT scanning and immunohistochemical (IHC) analysis of osteocalcin (Ocn), Indian Hedgehog (Ihh), Patched1 (Ptch1), and zinc finger protein GLI1 (Gli1). Subsequently, the Hh signaling pathway was activated using smoothened agonist (SAG) (10 mg/kg, gavage), and its potential to improve cranial defect healing in T1DM was assessed by MicroCT and IHC staining. Finally, the ability of SAG (1 000 nmol/L) to counteract the inhibitory effects of a high-glucose environment (25 mol/L) on osteogenic differentiation of mouse bone marrow mesenchymal stem cells (BMSCs) was investigated through in vitro experiments. Detection methods included Alkaline Phosphatase and Alizarin Red staining, as well as quantitative real-time PCR (qPCR) analysis of the osteogenesis-related genes Alp, Spp1, Bglap, and Sp7. Results: Akita mice exhibited early, stable, and significant spontaneous T1DM characteristics. On postoperative day 21, the newly formed bone in the cranial defect area of Akita mice showed significant decreases in the bone volume-to-tissue volume ratio, volumetric bone mineral density, and Ocn expression (P < 0.05), with significant downregulation of Ihh, Ptch1, and Gli1 (P < 0.05). Activation of the Hh signaling pathway by SAG significantly mitigated the negative impact of T1DM on cranial defect healing in Akita mice (P < 0.05). Moreover, after SAG treatment, the inhibitory effects of the high-glucose environment on the alkaline phosphatase activity and in vitro mineralization capacity of BMSCs were significantly alleviated (P < 0.05), and the expression levels of osteogenic differentiation-related genes were significantly upregulated (P < 0.05). Conclusion T1DM inhibits cranial defect healing in Akita mice by suppressing the expression of the Hh signaling pathway, whereas activation of the Hh signaling pathway promotes osteogenesis and ameliorates the inhibitory effects of T1DM on bone healing.

Objective To investigate the trends in the global burden due to cystic echinococcosis from 1990 to 2021, and to predict the global burden of cystic echinococcosis from 2022 to 2035, so as to provide insights into formulation of the cystic echinococcosis control strategy. Methods The global age-standardized prevalence, mortality, disability-adjusted life years (DALYs) rates and their 95% uncertainty intervals (UI) of cystic echinococcosis from 1990 to 2021 were captured from the Global Burden of Disease Study 2021 (GBD 2021) database, and the trends in the global burden of cystic echinococcosis from 1990 to 2021 were analyzed using the Joinpoint regression model. The associations between the global burden of cystic echinococcosis and socio-demographic index (SDI) were examined using a smoothing spline model and frontier analysis, and the global burden of cystic echinococcosis was projected from 2022 to 2035 using the Bayesian age-period-cohort (BAPC) model. Results The global agestandardized prevalence, mortality and DALYs rates of cystic echinococcosis were 7.69/10⁵ [95% UI: (6.27/10⁵, 9.51/10⁵)], 0.02/10⁵ [95% UI: (0.01/10⁵, 0.02/10⁵)], and 1.32/10⁵ [95% UI: (0.99/10⁵, 1.69/10⁵)] in 2021. The global age-standardized prevalence of cystic echinococcosis appeared a tendency towards a rise by 0.14% per year from 1990 to 2021, and the global age-standardized mortality and DALYs rates of cystic echinococcosis appeared a tendency towards a decline by 4.68% and 4.01% per year from 1990 to 2021, respectively. Joinpoint regression analysis showed that global age-standardized prevalence of cystic echinococcosis appeared a tendency towards a decline from 1990 to 2000 [annual percent change (APC) = −0.66%, 95% confidence interval (CI): (−0.70%, −0.61%)] and from 2005 to 2015 [APC = −0.88%, 95% CI: (−0.93%, −0.82%)], and towards a rise from 2000 to 2005 [APC = 3.68%, 95% CI: (3.49%, 3.87%)] and from 2015 to 2021 [APC=0.30%, 95%CI: (0.19%, 0.40%)].Theagestandardized prevalence (r = −0.17, P < 0.05), mortality (r = −0.67, P < 0.05) and DALYs rates of cystic echinococcosis (r = −0.60, P < 0.05) all correlated negatively with SDI across 21 geographical regions from 1990 to 2021, and the age-standardized mortality (r = −0.61, P < 0.05) and DALYs rates (r = −0.44, P < 0.05) both correlated negatively with SDI across 204 countries and territories in 2021. Frontier analysis revealed that the age-standardized DALYs rate of cystic echinococcosis was still not in line with the frontier in some high-SDI countries or territories. In addition, the global age-standardized prevalence was projected with the BAPC model to appear a tendency towards a rise among both men [estimated annual percent change (EAPC) = 0.18%, 95% CI: (0.13%, 0.23%)] and women [EAPC = 0.29%, 95% CI: (0.24%, 0.34%)] from 2022 to 2035, and the global age-standardized mortality [men: EAPC = −4.71%, 95% CI: (−4.71%, −4.37%); women: EAPC = −4.74%, 95% CI: (−4.74%, −4.74%)] and DALYs rates [men: EAPC = −3.35%, 95% CI: (−3.36%, −3.34%); women: EAPC = −3.17%, 95% CI: (−3.18%, −3.16%)] were projected to appear a tendency towards a decline among both men and women. Conclusions The global burden of cystic echinococcosis appeared an overall tendency towards a decline from 1990 to 2021; however, the global prevalence of cystic echinococcosis is projected to appear a tendency towards a rise from 2022 to 2035. Intensified cystic echinococcosis control programmes are recommended.

Abstact:Objective To investigate the gene expression differences between left-sided colon cancer and right-sided colon cancer and the mechanism differences between the colorectal cancer core drug pairs of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba acting on left-sided and right-sided colon cancer.Methods The transcriptome data of 134 patients with left-sided colon cancer and 194 patients with right-sided colon cancer from The Cancer Genome Atlas(TCGA)were downloaded,and the R software was applied to realize the differential gene analysis of the two groups and the enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway;the BATMAN-TCM database was used to obtain the active ingredients and targets of the drug pair of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba,and based on the different genes of the left-and right-sided colon cancers,KEGG enrichment analysis of the drug pair-left/right-sided colon cancers was performed respectively,and the protein-protein-interaction(PPI)network was constructed to compare the differences of the biosignaling pathways enriched by the drug pairs for the treatment of left-and right-sided colon cancers,as well as the differences of the key target points.Results There were 6 051 differentially expressed genes common to left-and right-sided colon cancers relative to normal paracancerous tissues,1958 differentially expressed genes specific to left-sided colon cancer,and 1739 differentially expressed genes specific to right-sided colon cancer;14 KEGG-enriched pathways specific to left-sided colon cancer,and 23 KEGG-enriched pathways specific to right-sided colon cancer.There were 85 active compounds in the drug-pair of Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba,corresponding to a total of 469 targets.The drug-pair-left-sided colon cancer targets were enriched in 10 KEGG signaling pathways,with the key targets being DRD2,CACNA1C,HTR3A,COMT,and TH;and the drug-pair-right-sided colon cancer targets were enriched in 1 KEGG signaling pathway,with the core targets being HTR3A,DRD2 TH,AGT,GRIN2B.Conclusion There are gene expression differences between left-and right-sided colon cancers:left-sided colon cancer is associated with abnormal immune function,abnormal AMPK signaling pathway and other mechanisms,and right-sided colon cancer is associated with neutrophil extracellular trap formation,alcoholism,abnormal Hippo signaling pathway and other mechanisms.In addition to regulating cell cycle and essential amino acid metabolism and other mechanisms,Sophorae Flavescentis Radix-Sargentodoxae Caulis-Scutellariae Barbatae Herba drug pairs have specific effects on regulating the intestinal endocrine function of the left-sided colon cancer,inhibiting inflammatory response of the right-sided colon cancer,and may also have mood-regulating effects on patients with colon cancer.

The working principle and development of flexible semiconductor devices based on organic field effect transistor(OFET)technology were introduced.The current research status of OFET-based wearable flexible monitoring devices were reviewed,including biomechanical monitoring devices,tattoo biomonitoring devices and cellular detection devices and etc.The deficiencies of OFET-based wearable flexible monitoring devices were analyzed,and it's pointed out that miniaturization,personalization and diversification were the directions for the development of the future OFET-based wearable flexible moni-toring devices.[Chinese Medical Equipment Journal,2024,45(1):93-100]

Objective To analyze the influence of midazolam and propofol on sedation effect and blood gas indicators in elderly patients undergoing mechanical ventilation after cardiopulmonary bypass(CPB)cardiac surgery.Methods The elderly patients with mechanical ventilation after CPB cardiac surgery were grouped according to cohort method,including midazolam group(group M),propofol group(group P)and midazolam-propofol combined administration group(group M-P).Group M was treated with midazolam(intravenous injection of 0.05-0.10 mg kg-1 midazolam for sedation induction,and then continuously intravenous injection of 0.05-0.15 mg·kg-1·h-1 midazolam by micropump),and group P was treated with propofol(intravenous injection of 0.5 mg·kg-1 propofol for sedation induction,and then continuously intravenous injection of 0.5-2.0 mg·kg-1·h-1 propofol by micropump),and group M-P was given combined administration of midazolam and propofol(intravenous injection of 0.02-0.05 mg·kg-1 midazolam and 0.2-0.5 mg·kg-1 propofol for sedation induction and then continuously intravenous pump of 0.05-0.1 mg·kg-1 midazolam and 0.5-0.8 mg·kg·h-1 propofol).The sedation effect,blood gas indicators,hemodynamic indicators,extubation time,intensive care unit(ICU)stay time and treatment cost were compared among the three groups,and the adverse drug reactions during sedation therapy were recorded.Results There were 43 cases in group M,44 cases in group P,39 cases in group M-P.The drug onset times in groups M,P and M-P were(77.94±12.05),(18.18±5.20)and(21.25±9.36)s;the times to achieve satisfactory sedation effect were(42.57±11.41),(22.63±8.17)and(23.98±10.25)min;the recovery times after withdrawal were(59.30±14.86),(19.83±5.44)and(22.16±6.29)min;the extubation times were(1.61±0.20),(1.45±0.22)and(1.37±0.15)d;the ICU stay times were(2.17±0.29),(1.91±0.36)and(1.84±0.25)d;the treatment costs were(186.59±60.83),(922.97±164.34)and(375.03±71.16)thousand yuan;and the total incidence rates of adverse drug reactions were 34.88％,4.55％and 7.69％respectively,all with significant difference(all P＜0.05).There were no statistically significant differences in mean arterial pressure(MAP),heart rate(HR),oxygen saturation(SpO2),partial pressure of oxygen(PaO2),partial pressure of carbon dioxide(PaCO2)at T0,T1,T2,T3 and T4 among the three groups(all P＞0.05).Conclusion Combined administration of midazolam and propofol in elderly patients underwent mechanical ventilation after CPB cardiac surgery has a significant sedation effect,and it is conducive to reducing the dosages of sedative drugs,and it has small impact on blood gas indicators and hemodynamic indicators of patients.Compared with midazolam alone,it is more beneficial to shortening the extubation time and ICU stay and reducing the total incidence rate of adverse drug reactions,and compared with propofol alone,it is more beneficial to reducing treatment cost,and is a more ideal sedation administration model.

Objective To investigate the interventional effects of Icariin(IC A)combined with prednisone acetate tablets(PAT)in rats with steroid-resistant nephrotic syndrome(SRNS)model.Methods Male SD rats were used to construct the SRNS model with 2 injections of adriamycin(ADR),and were randomly divided into the model group,PAT group,ICA group,and the combined group,with 10 rats in each group after successful modeling;another 10 rats were taken as the blank group.The blank and model groups were given 0.9％NaCl;the PAT group was given 6.3 mg·kg-1·d-1 PAT;the ICA group was given 50 mg·kg-1·d-1 ICA;and the combined group was given 6.3 mg·kg-1·d-1 PAT+50 mg·kg-1·d-1 ICA.The volume of gavage of the five groups of rats was 1 mL·100 g-1,and the drug was administered once a day for 6 weeks.The renal function and blood lipid level of rats in each group were compared;the expression of calcium/calmodulin dependent protein kinase Ⅱ α(CaMK Ⅱα),cofilin-1 and F-actin were detected by Western blotting.Results Urinary protein quantification values at 8 weeks in blank,model,PAT,ICA and combined groups were(6.66±1.48),(178.38±8.96),(161.56±5.49),(157.13±8.32)and(96.90±5.05)mg·24 hi-1;serum creatinine levels were(30.90±1.79),(41.10±2.77),(34.90±2.03),(35.10±2.18)and(31.90±2.47)μmol·L-1;triglycerides levels were(0.87±0.14),(2.30±0.41),(1.94±0.44),(1.17±0.59)and(0.89±0.30)mmol·L-1;total cholesterol levels were(1.54±0.08),(2.53±0.22),(2.14±0.59),(2.27±0.31)and(1.93±0.32)mmol·L-1;the relative expression levels of CaMK Ⅱ α proteins were 0.88±0.09,0.65±0.06,0.71±0.08,0.76±0.07 and 0.88±0.08;the p-Cofilin-1/Cofilin-1 ratios were 0.56±0.27,2.52±0.04,0.75±0.02,0.91±0.20 and 0.53±0.05;the relative expression levels of F-actin protein were 0.93±0.01,0.64±0.01,0.75±0.02,0.80±0.01 and 0.85±0.00,respectively.The differences of the above indexes in the model group were statistically significant compared with those in the blank group and the combined group(all P＜0.05).Conclusion ICA combined with PAT can improve renal function,lipid levels,improve renal histopathological structure,and promote skeletal protein remodeling in SRNS rats by regulating CaMK Ⅱ α/Cofilin-1/F-actin pathway.

Renal fibrosis is a common pathological manifestation of all chronic kidney diseases.Ferroptosis is closely related to the pathogenesis of renal fibrosis and can influence the onset of renal fibrosis,and it is the most critical step in the development of renal fibrosis.The paper describes the relationship between ferroptosis and renal fibrosis,discusses the research progress of ferroptosis on renal fibrosis,and further summarizes,analyzes,and describes the effective and highly targeted natural active ingredients of traditional Chinese medicines against ferroptosis,and concludes that the reversal of renal fibrosis is achieved through the regulation of the key targets of ferroptosis,with a view to providing a broad new direction for its prospects in the field of renal fibrotic disease prevention and treatment;and to provide a scientific guide for clinical treatment and basis for clinical treatment.

Objective To study the common basis and association between sickness behaviour and occurrence of classical symptoms of kidney yang deficiency of rats with adriamycin nephropathy.Methods The SD rats were given adriamycin by tail-vein injection for 2 times(4.0 and 3.5 mg·kg-1,one week apart)to construct the model of nephrotic syndrome with Chinese medicine symptom of kidney yang deficiency.After successful modeling,the model rats were randomly divided into adriamycin group(ADR group),corticosterone group(CORT group)and hydrocortisone group(HYD group),with 12 rats per group;another 12 normal rats were taken as normal group.In the HYD group,25 mg·kg-1·d-1 HYD was administered for 14 d to establish kidney yang deficiency model with simple hypothalamus-pituitary-adrenal cortex(HPA)axis inhibition.CORT group was adding 25 μg·mL-1 corticosterone to the water for 6 weeks,and the others drinking water supplied.The levels of urinary 17-hydroxy steroid were measured by enzyme linked immunosorbent assay.Glucocorticoid receptor(GR)and nuclear factor-kappa B(NF-κB)protein expression levels in kidney and hypothalamus were detected by Western blotting.Results In the normal,ADR,CORT and HYD groups,the urinary 17-hydroxysteroid levels were(19.14±1.94),(10.07±1.62),(20.30±1.55)and(14.23±2.37)μg·L-1;the relative expression levels of GR protein in hypothalamic were 0.63±0.05,0.11±0.05,0.85±0.08 and 0.35±0.06;the relative expression levels of NF-κB protein in hypothalamic were 0.06±0.03,0.96±0.03,0.59±0.01 and 0.23±0.04;the relative expression levels of GR protein in kidney tissue were 0.94±0.06,0.06±0.02,0.40±0.02 and 0.09±0.08;the relative expression levels of NF-κB protein in kidney tissue were 0.07±0.05,0.81±0.12,0.72±0.07 and 0.49±0.08,respectively.Compared with the ADR and HYD groups,the above indexes in the normal group were statistically significant(P＜0.05,P＜0.01).And compared with the ADR group,the relative expression levels of NF-κB protein in renal tissue with CORT group were not statistically significant(P＞0.05),but the other indexes in CORT group were statistically significant(all P＜0.01).Conclusion HPA axis dysfunction with GR damaged and activated inflammatory levels are the common basis for the combination of typical symptoms of kidney yang deficiency and sickness behaviour which characterised by"deficiency and cold syndrome".

From the perspective of the physiological basis of liver and kidney sharing the common source in traditional Chinese medicine(TCM),and by integrating the theory of kidney dominating bone,liver dominating tendon,and meridian sinew of TCM as well as the bone resorption and collapse theory,and non-uniform settlement theory and lower-limb musculoskeletal bowstring structure theory of modern orthopedics,the pathogenesis of osteonecrosis of the femoral head(ONFH)under the system of non-uniform settlement during bone resorption and multidimensional composite bowstring working in coordination with the theory of liver-kidney and muscle-bone was explored.The key to the TCM pathogenesis of ONFH lies in the deficiency of the liver and kidney,and then the imbalance of kidney yin-yang leads to the disruption of the dynamic balance of bone formation and bone resorption mediated by osteoblasts-osteoclasts,which manifests as the elevated level of bone metabolism and the enhancement of focal bone resorption in the femoral head,and then leads to the necrosis and collapse of the femoral head.It is considered that the kidney dominates bone,liver dominates tendon,and the tendon and bone together constitute the muscle-bone-joint dynamic and static system of the hip joint.The appearance of collapse destroys the originally balanced muscle-bone-joint system.Moreover,the failure of liver blood in the nourishment of muscles and tendons further exacerbates the imbalance of the soft tissues around the hip joint,accelerates the collapse of the muscle-bone-joint dynamic and static system,speeds up the process of femoral head collapse,and ultimately results in irreversible outcomes.Based on the above pathogenesis,the systematic integrative treatment of ONFH should be based on the TCM holistic concept,focuses on the focal improvement of internal and external blood circulation of the femoral head by various approaches,so as to rebuild the coordination of joint function.Moreover,attention should be paid to the physical constitution of the patients,and therapy of tonifying the kidney and regulating the liver can be used to restore the balance between osteogenesis and osteoblastogenesis,and to reconstruct the muscle-bone-joint system,so as to effectively delay or even prevent the occurrence of ONFH.

Objective To assess the clinical short-term outcomes of implanting D-shant atrial shunt device(aSD)in a single center for patients with heart failure with reduced ejection fraction(HFrEF).Methods From January 2022 to January 2023,a retrospective analysis was conducted on 12 patients with HFrEF who underwent percutaneous implantation of a D-shant aSD.We assessed cardiac chamber size and ventricular function using echocardiography,right heart catheterization measurements and patient clinical indicators were collected,follow up data of 12 months postoperative and pre-implantation D-shant were compared.The primary endpoint of the study was the cumulative occurrence of adverse cardiac,neurologic,or renal events during the follow-up period.Secondary endpoints were improvements in functional status included cardiac function,quality of life,and exercise capacity.Results All 12 patients underwent successful percutaneous inter-atrial shunting procedures using the D-shant.Postoperative immediately fluoroscopy and echocardiography confirmed accurate localization and patency of the atrial shunt devices in all cases.Postoperative hemodynamic assessment revealed a significant decrease in pulmonary capillary wedge pressure[(29.8±3.4)mmHg vs.(17.8±0.8)mmHg,P＜0.001].During 12 months follow-up,the cumulative adverse event rate was 8.3％(one patient received a heart transplant),a significant reduction in left atrial diameter from(65.8±6.5)mm to(48.0±4.5)mm(P＜0.001)was observed.Furthermore,there was notable improvement in clinical cardiac function indices quality of life,and exercise capacity of the patients.Conclusions This single-center retrospective study found that the use of a D-shant aSD to perform percutaneous interatrial shunting in patients with HFrEF is safe and effective.Short-term follow-up demonstrated sustained patency of the shunt and that the intervention was associated with improved functional status.