Objective: To fabricate a hydrogel loaded with inositol hexaphosphate-zinc and preliminarily evaluate its performance in self-mineralization and osteoinduction, thereby providing a theoretical basis for the development of bone regeneration materials. Methods: The hydrogel framework (designated DF0) was formed by copolymerizing methacryloyloxyethyltrimethylammonium chloride and four-armed poly(ethylene glycol) acrylate, followed by sequentially loading inositol hexaphosphate anions via electrostatic interaction and zinc ions via chelation. The hydrogel loaded only with inositol hexaphosphate anions was named DF1, while the co-loaded hydrogel was named DF2. The self-mineralization efficacy of the DF0 , DF1 and DF2 hydrogels was characterized using scanning electron microscopy, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The biocompatibility was assessed via live/dead cell staining and a CCK-8 assay. The osteoinductive capacity of the DF0 , DF1 and DF2 hydrogels on MC3T3-E1 cells was assessed via alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. In the aforementioned cell experiments, cells cultured in standard medium served as the control group Results: The DF0, DF1, and DF2 hydrogels were successfully synthesized. Notably, DF1 and DF2 exhibited distinct self-mineralization within 6 days. Results from TEM, EDS, and SAED confirmed that the mineralization products were amorphous calcium phosphate in group DF1, and amorphous calciumzinc phosphate in group DF2. Biocompatibility tests revealed that none of the hydrogels (DF0, DF1, and DF2) adversely affected cell viability or proliferation. In osteogenic induction experiments, both ALP and ARS staining were intensified in the DF1 and DF2 groups, with the most profound staining observed in the DF2 group. Conclusion The developed inositol hexaphosphate-zinc hydrogel (DF2) demonstrates the dual capacity to generate calcium-phosphate compounds through self-mineralization while exhibiting excellent osteoinductive properties. This biocompatible, dual-promoting osteogenic hydrogel presents a novel strategy for bone regeneration.

OBJECTIVE To conduct a clinical rapid evaluation of the marketed proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors in China， including evolocumab， tafolecimab， recaticimab， ebronucimab， ongericimab and inclisiran. METHODS Based on the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions （second edition）， drug instructions， clinical diagnosis and treatment guidelines， and literature for six drugs were retrieved from CNKI， Wanfang Data， VIP， PubMed， Embase， Cochrane Library and related official websites. The clinical rapid evaluation was conducted from five aspects： pharmaceutical characteristics， effectiveness， safety， economy， and other attributes. RESULTS The pharmaceutical characteristics， effectiveness， safety， economy， other attributes， and total score of evolocumab scored 24， 27， 15.7， 10， 5.3， and 82 points， respectively. Tafolecimab scored 23.5， 23， 11.5， 9.97， 4.6， and 72.57 points， respectively. Recaticimab scored 20.5， 22， 15.5， 6.37， 3.5， and 67.87 points. Ebronucimab scored 20， 23， 11， 6.48， 3.5， and 63.98 points. Ongericimab scored 20.5， 23， 8.5， 4.83， 3.5， and 60.33 points. Inclisiran scored 25.5， 24， 13， 6.48， 5， and 73.98 points. CONCLUSIONS Evolocumab is the optimal choice for treating hypercholesterolemia and is recommended as the first-line option. Tafolecimab is the second-line option， and recaticimab is suitable for patients who are sensitive to drug adverse reactions. Inclisiran is suitable for patients with poor compliance. Ebronucimab and ongericimab are weakly recommended due to their later market introduction. Clinicians should make individualized drug selections based on factors such as patient risk level and compliance requirements.

Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM₁, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.

ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

Objective To evaluate the longitudinal imaging features of coronary artery plaques in elderly male patients with CHD and myocardial bridges and explore the longitudinal changing pat-terns.Methods A total of 117 elderly male CHD patients who underwent two examinations of coronary computed tomography angiography in our medical center from January 2018 to Septem-ber 2023 were enrolled in this study.Then 216 small plaques(0.1-50 mm3 in size)were subjec-ted,and classified into the proximal myocardial bridge group(98 plaques)and other heart part group(118 plaques)according to the site of the plaques.Plaque volume,plaque composition vol-ume,FAI,and CT-derived fraction flow reserve(CT-FFR)were calculated and recorded.Results In the 2 groups of plaques,there were no statistically differences in the plaque length,plaque nec-rotic core volume,and FAI derived from the second examination than the baseline one(P＞0.05).The plaque volume,intra-plaque fibers,and dense calcified volume of plaques in the second exami-nation were significantly greater than those at baseline,and CT-FFR was obviously smaller than the baseline level in both groups(P＜0.05,P＜0.01).In the proximal myocardial bridge group,the intra-plaque fibrofat volume in the second examination was significantly larger than that of baseline,while opposite phenomenon was observed in the plaques of the other heart part group(P＜0.05).The annual changing rates of intraplaque fibrofat volume and FAI were significantly higher in the proximal myocardial bridge group than the other heart part group[0.51％(-0.32％,0.51％)vs 0.02％(-0.46％,0.20％),P=0.046;0.55％(-2.44％,1.76％)vs 0.33％(-1.36％,2.63％),P=0.044].Conclusion In elderly male patients,the intraplaque fibrofat vol-ume,FAI and CT-FFR are more likely to change in the proximal plaques of the left anterior de-scending artery myocardial bridge than the plaques of other parts of heart,so the proximal plaques of the left anterior descending artery need more clinical attention and early intervention.

Objective To investigate the effect of the rs3765467 polymorphism of glucagon-like peptide-1 receptor(GLP-1R)gene on the efficacy of Liraglutide(Lir)in patients with type 2 diabetes mellitus(T2DM)and metabolic associated fatty liver disease(MAFLD).Methods A total of 281 patients with T2DM from May 2022 to May 2023 were selected,including 125 patients with simple T2DM(T2DM group)and 156 patients with T2DM combined with MAFLD(T2DM+MAFLD group).120 healthy individuals during the same period were selected as the control(NC)group.The related indexes of glucose and lipid metabolism were detected.The polymorphism of GLP-1R gene rs3765467 was detected.Results BMI,FPG,HbA1c,HOMA-IR and TG in each group increased in turn(P<0.05),while the distribution frequency of genotype GG and allele G decreased in turn(P<0.05).TC and LDL-C in T2DM and T2DM+MAFLD groups were higher than those in NC group(P<0.05).TC and TG levels in genotype GA/AA patients were significantly higher than those in genotype GG patients(P<0.05).Compared with before treatment,the levels of BMI,FPG,HbA1c,HOMA-IR,TC,TG and LDL-C in T2DM patients with MAFLD were significantly decreased after Lir treatment(P<0.05).There was no significant difference in BMI and related indexes of glucose and lipid metabolism in GG and GA/AA patients before and after Lir treatment(P>0.05).Conclusions The distribution frequency of GG and G allele at rs3765467 of GLP-1R gene is reduced in T2DM patients with MAFLD.The carrying of allele A was associated with increased TC and TG levels,but did not affect the efficacy of Lir in reducing weight and improving glycolipid metabolism.

Objective To investigate the role and mechanism of AMP-activated protein kinase(AMPK)in regulating mitochondrial function and cardiomyocyte injury in sepsis.Methods Forty Balb/c mice were randomly divided into four groups:Sham group(n=10),Sham+5-aminoimidazole-4-carboxamide ribonucleotide(AICAR)group(n=10),CLP group(n=10),and CLP+AICAR group(n=10).A sepsis mouse model was established through cecal ligation and puncture(CLP).Echocardiography and histological analysis were used to assess sepsis-induced cardiac injury.Neonatal rat cardiomyocytes(NRCMs)were incubated with lipopolysaccharide(LPS)(10 μg/mL)for 24 h to induce an in vitro sepsis model,and treated with AICAR.Mitochondrial function and dynamics were assessed by using Western blotting,enzyme-linked immunosorbent assay(ELISA),and immunofluorescence assays.Results Compared with the Sham group,AMPK expression in the myocardial tissue of CLP mice was significantly reduced(P<0.05).Compared with the CLP group,AMPK expression in the CLP+AICAR group was significantly increased(P<0.05).Survival analysis showed that CLP led to a high mortality rate(～60％ ),while AICAR treatment significantly improved the survival rate of CLP mice(P<0.05).Compared with the Sham group,cardiac output(CO),stroke volume(SV),and left ventricular end-diastolic volume(LVEDV)were significantly decreased in the CLP group(P<0.05),while left ventricular posterior wall systolic(LVPWs)and left ventricular posterior wall thickness(LVPWd)were significantly increased(P<0.05).AICAR treatment alleviated the cardiac dysfunction induced by CLP.Compared with the CLP group,mitochondrial size and the number of mitochondrial cristae in the myocardial tissue of CLP+AICAR group mice were significantly increased(P<0.05),while DHE fluorescence intensity and the number of TUNEL-positive cells were significantly reduced(P<0.05).Compared with the LPS group,ATP production,mitochondrial respiration rate,and complex Ⅰ,Ⅱ,and Ⅲ activities in NRCMs of the LPS+AICAR group were significantly increased(P<0.05),while mitochondrial and cytoplasmic ROS levels were significantly reduced(P<0.05).Compared with the control group,mitochondrial size in NRCMs of the LPS group was significantly reduced(P<0.05),while Bax and Caspase-3 expression,as well as mitochondrial fission index,were significantly increased(P<0.05),and these changes were mitigated by AICAR(P<0.05).Conclusion AMPK plays a crucial role in maintaining cardiac function and mitigating septic myocardial injury by regulating mitochondrial structure and function,energy metabolism,oxidative stress,and apoptosis.

Objective Comparing the clinical efficacy of moxifloxacin and azithromycin in the treatment of Mycoplasmal pneumoniae pneumonia(MPP).Methods MPP patients admitted to our hospital from January 2023 to May 2024 were selected and randomly divided into the observation group and the control group.Both groups were given conventional treatment such as salbutamol and budesonide aerosol inhalation.Additionally,the control group was given azithromycin 0.5 g,ivd,qd,and the observation group was given moxifloxacin 0.4 g,ivd,qd.After one week of treatment,the efficacy,symptom disappearance time and adverse drug reactions occurrence of the two groups were compared.The serum inflammatory markers[white blood cell count(WBC),interleukin-6(IL-6),C-reactive protein(CRP),procalcitonin(PCT)],immunoglobulin indicators(IgA,IgG,IgM),T lymphocyte subset indicators(CD3+,CD4+,and CD4+/CD8+)before and after treatment were compared between the two groups.Results A total of 80 patients were included and each group was 40 patients.After treatment,the total effective rate of observation group(95.00％)was higher than that of control group(75.00％)(P＜0.05).The disappearance time of symptoms(cough,fever,and lung rales)in the observation group was significantly lower than that in the control group(P＜0.05).After treatment,the levels of CD3+,CD4+,and CD4+/CD8+in both groups significantly increased,while the levels of serum IL-6,CRP,PCT,WBC,IgA,IgM,and IgG significantly decreased(P＜0.05),with the observation group showing better results(P＜0.05).There was no significantiy difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Moxifloxacin is more effective than azithromycin in the treatment of MPP,which can relieve symptoms,improve immune function,reduce inflammatory response,and has a relatively good safety profile.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.