Traditional treatment for type 1 diabetes mellitus （T1DM） primarily involves insulin replacement， yet some patients encounter issues such as significant blood glucose fluctuations， high risk of hypoglycemia， and weight gain. In recent years， the adjuvant therapeutic role of non-insulin hypoglycemic drugs in T1DM has gradually gained attention. This article reviews the mechanisms of action and clinical research progress of five types of non-insulin hypoglycemic drugs in the treatment of T1DM： amylin analogues （pramlintide）， biguanides （metformin）， sodium-glucose co-transporter 2 inhibitor， dipeptidyl peptidase-4 inhibitor， and glucagon-like peptide-1 receptor agonist. It is found that these drugs can enhance clinical benefits for T1DM patients by improving insulin sensitivity， delaying gastric emptying， promoting urinary glucose excretion， and regulating incretin levels， thereby reducing glycated hemoglobin levels， decreasing insulin dosage， and managing body weight. Simultaneously， these drugs also present limitations such as low patient compliance due to complex dosing regimens， increased risk of diabetic ketoacidosis， and heterogeneity in glycemic control. Future research could focus on developing individualized treatment strategies， combining pharmacogenomics with novel biomarkers to precisely identify subpopulations of patients who may benefit， and delving into the potential value of these drugs in delaying diabetic vascular complications and improving patients’ quality of life.

Objective:To discuss the effect of acupuncture on the differentiation and apoptosis of quadriceps muscle satellite cells in model rats with knee osteoarthritis(KOA),and to clarify its related mechanism.Methods:A total of 40 SPF-grade rats were selected and randomly divided into control group,model group,celecoxib group,and acupuncture group,with 10 rats in each group.The rats in control group only underwent joint cavity incision followed by suturing,while the rats in model group,celecoxib group,and acupuncture group were used to replicate the KOA models.The maximum circumference of the femoral segment of the affected limb,rat body mass,and quadriceps wet weight of the rats in various groups were measured;the quadriceps wet weight maintenance rate and quadriceps wet weight/body mass ratio of the rats in various groups were calculated.HE staining was used to observe the pathomorphology of articular cartilage and quadriceps muscle tissue of the rats in various groups;terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL)method was used to detect the apoptosis indexes in articular cartilage and quadriceps muscle tissue of the rats in various groups;immunofluorescence method was used to detect the protein expression levels of interleukin-6(IL-6),Janus kinase(JAK),and signal transducer and activator of transcription 3(STAT3)in quadriceps muscle tissue of the rats in various groups;Western blotting method was used to detect the expression levels of IL-6/JAK/STAT3 signaling pathway proteins,and muscle satellite cells,and apoptosis-related proteins in quadriceps muscle tissue of the rats in various groups.Results:Compared with control group,the affected hind limb circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight/body mass ratio of the rats in model group were significantly decreased(P<0.05);compared with model group,the affected hind limb circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight/body mass ratio of the rats in celecoxib group and acupuncture group were significantly increased(P<0.05);compared with celecoxib group,the affected hind limb circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight/body mass ratio of the rats in acupuncture group were significantly increased(P<0.05).The HE staining results showed that the knee articular cartilage of the rats in control group remained intact,chondrocytes were aggregated and horizontally arranged with smooth edges,and quadriceps muscle cells were long cylindrical,orderly arranged,and regular in shape;in model group,the knee articular cartilage was thinner with rough edges,reduced number of cartilage layers,and disordered arrangement,and the quadriceps muscle fibers were disorganized,with some muscle fiber dissolution and muscle cell membrane damage,accompanied by muscle fiber fragments and a large amount of inflammatory exudate;in celecoxib group,the morphology of knee articular cartilage was generally normal,occasionally with irregular cartilage arrangement and reduced thickness,sporadically visible necrotic chondrocytes,quadriceps muscle fibers and sarcolemma were relatively intact,new muscle fibers appeared,some muscle fiber edges were blurred,accompanied by a small amount of cell debris and mild inflammatory infiltration;in acupuncture group,the knee articular cartilage structure remained intact with smooth edges,occasionally rough edges,and chondrocytes were aggregated and orderly arranged.The TUNEL assay results showed that compared with control group,the apoptosis indexes in articular cartilage and quadriceps muscle tissue of the rats in model group were significantly increased(P<0.05);compared with model group,the apoptosis indexes in articular cartilage and quadriceps muscle tissue of the rats in celecoxib group and acupuncture group were significantly decreased(P<0.05);compared with celecoxib group,the apoptosis index in articular cartilage and quadriceps muscle tissue of the rats in acupuncture group were significantly decreased(P<0.05).The immunofluorescence assay results showed that compared with control group,the expression levels of IL-6,JAK,and STAT3 proteins in quadriceps muscle tissue of the rats in model group were significantly decreased(P<0.05);compared with model group,the expression levels of IL-6,JAK,and STAT3 proteins in quadriceps muscle tissue of the rats in celecoxib group and acupuncture group were significantly increased(P<0.05);compared with celecoxib group,the expression levels of IL-6,JAK,and STAT3 proteins in quadriceps muscle tissue of the rats in acupuncture group were significantly increased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of IL-6,JAK,STAT3,paired box transcription factor 7(Pax7),Desmin,Myosin,and Myogenin proteins in quadriceps muscle tissue of the rats in model group were significantly decreased(P<0.05);compared with model group,the expression levels of IL-6,JAK,STAT3,Pax7,Desmin,Myosin,and Myogenin proteins in quadriceps muscle tissue of the rats in celecoxib group and acupuncture group were significantly increased(P<0.05);compared with celecoxib group,the expression levels of IL-6,JAK,STAT3,Pax7,Desmin,Myosin,and Myogenin proteins in quadriceps muscle tissue of the rats in acupuncture group were significantly increased(P<0.05).Compared with control group,the expression levels of B-cell lymphoma 2(Bcl-2),B-cell lymphoma-xl(Bcl-xl),and myeloid cell leukemia 1(MCL1)proteins in quadriceps muscle tissue in model group were significantly decreased(P<0.05),and the expression levels of Bcl-2-associated X protein(Bax)and cysteinyl aspartate specific proteinase-3(Caspase-3)proteins were significantly increased(P<0.05);compared with model group,the expression levels of Bcl-2,Bcl-xl,and MCL1 proteins in quadriceps muscle tissue of the rats in celecoxib group and acupuncture group were significantly increased(P<0.05),and the expression levels of Bax and Caspase-3 proteins were significantly decreased(P<0.05);compared with celecoxib group,the expression levels of Bcl-2,Bcl-xl,and MCL1 proteins in quadriceps muscle tissue of the rats in acupuncture group were significantly increased(P<0.05),and the expression levels of Bax and Caspase-3 proteins were significantly decreased(P<0.05).Conclusion:Acupuncture can promote the differentiation of quadriceps muscle satellite cells and inhibit muscle cell apoptosis in the model rats with KOA,and the mechanism may be related to the up-regulation of expressions of IL-6,JAK,and STAT3 proteins in the quadriceps muscle tissue.

Objective To investigate the effects of meridian and tendon acupuncture on the mitochondrial apoptosis of quadriceps femoris muscle cells in model rats of knee osteoarthritis(KOA);To explore its mechanism for the treatment of KOA.Methods Totally 40 SPF healthy male Wistar rats were randomly divided into sham-operation group(10 rats)and modeling group(30 rats).The modified Hulth method was used to establish a KOA rat model.The model rats were randomly divided into model group,celecoxib group and meridian and tendon acupuncture group,with 9 rats in each group.Corresponding intervention measures were given to each group for 14 consecutive days.Improved Lequesne MG score was used for evaluating knee joint function in rats,measuring thigh circumference,quadriceps femoris wet weight,wet weight maintenance rate and wet weight ratio of the affected limb,HE staining was used to observe the morphology of quadriceps femoris tissue,TUNEL method was used to detect apoptosis of quadriceps femoris cells,immunofluorescence was used to detect the expressions of reactive oxygen species(ROS),superoxide dismutase(SOD),Caspase-3 and Caspase-9 in quadriceps femoris muscle tissue,fluorescence double staining method was used to detect the co-expression of ROS and Caspase-3 in quadriceps femoris tissue,Western blot was used to detect the expressions of apoptosis related proteins in quadriceps femoris tissue.Results Compared with the sham-operation group,the improved Lequesne MG score of the knee joint in the model group rats increased(P<0.05),the circumference of the thigh,wet weight of the quadriceps femoris,wet weight maintenance rate and wet weight ratio of the affected limb decreased(P<0.05),the arrangement of quadriceps femoris muscle fibers was disordered and loose,with some muscle fibers dissolved and necrotic,accompanied by a large amount of inflammatory exudate,an increase in lymphocytes,and an increase in cell apoptosis index(P<0.05),the expressions of ROS,Caspase-3 and Caspase-9 in quadriceps femoris tissue increased,while the expression of SOD decreased(P<0.05),the protein expressions of Bcl-2,Bcl-XL,Bax,Cytochrome C(CytC),Caspase-3 and Caspase-9 in quadriceps femoris tissue increased(P<0.05).Compared with the model group,the improved Lequesne MG scores of the knee joint in the celecoxib group and the meridian and tendon acupuncture group decreased(P<0.05),while thigh circumference,quadriceps femoris wet weight,wet weight maintenance rate,wet weight ratio increased(P<0.05),the structure of quadriceps femoris muscle fibers was normal,the muscle membrane was relatively intact,the apoptosis index decreased(P<0.05),the expressions of ROS,Caspase-3 and Caspase-9 in quadriceps femoris tissue decreased,while the expression of SOD increased(P<0.05),the protein expressions of Bcl-2,Bcl-XL,Bax,CytC,Caspase-3 and Caspase-9 in quadriceps femoris muscle tissue decreased(P<0.05),and the expression trend of ROS and Caspase-3 in fluorescent double staining was consistent.Conclusion Meridian and tendon acupuncture can reduce ROS in the quadriceps femoris tissue of KOA model rats,inhibit the expressions of mitochondrial apoptosis-related proteins,thereby improving skeletal muscle strength,and play a certain therapeutic role.

Objective To investigate the relationship between sleep disorders and coronary heart disease through big data combined with Mendelian randomization analysis.Methods Data from 2005 to 2018 National Health and Nutrition Examination Survey in the United States were utilized.Logistic regression analysis was employed to evaluate the association between sleep disorders and coronary heart disease,while analyzing relevant influencing factors.A two-sample Mendelian randomization approach was implemented using Genome-Wide Association Studies to establish causal relationships.Results Logistic regression analysis demonstrated a significant association between sleep disorders and coronary heart disease(P＜0.001),with the neutrophil-to-lymphocyte ratio serving as a mediating factor in this relationship(P＜0.001).Mendelian randomization analysis revealed a positive correlation between sleep disorders and coronary heart disease(OR=1.030,95％CI:1.01-1.04).Conclusion Sleep disorders can increase the risk of coronary heart disease by activating inflammatory factors.

Objective To explore the mechanism of acupuncture protection of quadriceps muscle cells in knee osteoarthritis model rats based on Piezo1/YAP/Caspase3 axis.Methods 40 SPF grade Wistar rats were selected and adaptively fed for 7 days before being divided into three groups:sham surgery group,model group,western medicine group,and acupuncture group,with 10 rats in each group,according to a random control table.The model group,Western medicine group,and acupuncture group used the modified Hulth method to construct knee osteoarthritis models,while the sham surgery group only cut open the joint cavity and sutured it.After successful model replication,the sham surgery group was given physiological saline by gavage,the western medicine group was given celecoxib solution by gavage,and the acupuncture group was given acupuncture at the infrapatellar,crane top,and blood sea levels.Each group was intervened once a day for 14 consecutive days.During the treatment period,the rats continued to undergo treadmill training.After the intervention,the hematoxylin eosin staining method(HE)was used to detect the morphological changes of various rat quadriceps muscle tissues and articular cartilage;TUNEL method was used to detect apoptosis of quadriceps muscle cells,immunofluorescence method was used to detect the protein expression of Piezo1,YAP,and p-YAP in quadriceps muscle cells,Western blot method was used to detect the expression of anti apoptotic proteins CTGF,AREG,Gli2,AFP in quadriceps muscle tissue,as well as the protein expression levels of apoptosis related proteins Bcl-2,Bcl-xl,Bax,cytc,and Caspase3.Results Compared with the model group,the western medicine group and the acupuncture group had higher thigh circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight to body weight ratio(P<0.05).Compared with the western medicine group,the acupuncture group had higher thigh circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight to body weight ratio(P<0.05).Compared with the model group,the apoptosis index of the quadriceps muscle in the Western medicine group and acupuncture group rats was lower,and the apoptosis index of the quadriceps muscle in the acupuncture group was lower(P<0.05).Compared with the model group,the Western medicine group and acupuncture group showed higher expression of Piezo1 and p-YAP proteins in the quadriceps femoris muscle tissue,lower expression of YAP protein,higher expression of CTGF,AREG,Gli2,AFP proteins,higher expression of Bcl-2 and Bcl-xl proteins,and lower expression of Bax,cytc,and Caspase3 proteins(P<0.05).Compared with the Western medicine group,the acupuncture group showed higher expression of Piezo1 and p-YAP proteins in the quadriceps muscle tissue,lower expression of YAP protein,higher expression of CTGF,AREG,Gli2,AFP proteins,higher expression of Bcl-2 and Bcl-xl proteins,and lower expression of Bax,cytc,and Caspase3 proteins(P<0.05).Conclusion Acupuncture increases the expression of Piezo1 protein in the quadriceps femoris muscle of knee osteoarthritis model rats,promotes the phosphorylation of YAP into the nucleus,thereby promoting proliferation,anti apoptotic proteins CTGF,AREG,Gli2,and AFP protein expression,inhibiting Caspase3-dependent mitochondrial apoptosis,and protecting muscle cells.

Objective To investigate the relationship between sleep disorders and coronary heart disease through big data combined with Mendelian randomization analysis.Methods Data from 2005 to 2018 National Health and Nutrition Examination Survey in the United States were utilized.Logistic regression analysis was employed to evaluate the association between sleep disorders and coronary heart disease,while analyzing relevant influencing factors.A two-sample Mendelian randomization approach was implemented using Genome-Wide Association Studies to establish causal relationships.Results Logistic regression analysis demonstrated a significant association between sleep disorders and coronary heart disease(P＜0.001),with the neutrophil-to-lymphocyte ratio serving as a mediating factor in this relationship(P＜0.001).Mendelian randomization analysis revealed a positive correlation between sleep disorders and coronary heart disease(OR=1.030,95％CI:1.01-1.04).Conclusion Sleep disorders can increase the risk of coronary heart disease by activating inflammatory factors.

Objective To investigate the effects of meridian and tendon acupuncture on the mitochondrial apoptosis of quadriceps femoris muscle cells in model rats of knee osteoarthritis(KOA);To explore its mechanism for the treatment of KOA.Methods Totally 40 SPF healthy male Wistar rats were randomly divided into sham-operation group(10 rats)and modeling group(30 rats).The modified Hulth method was used to establish a KOA rat model.The model rats were randomly divided into model group,celecoxib group and meridian and tendon acupuncture group,with 9 rats in each group.Corresponding intervention measures were given to each group for 14 consecutive days.Improved Lequesne MG score was used for evaluating knee joint function in rats,measuring thigh circumference,quadriceps femoris wet weight,wet weight maintenance rate and wet weight ratio of the affected limb,HE staining was used to observe the morphology of quadriceps femoris tissue,TUNEL method was used to detect apoptosis of quadriceps femoris cells,immunofluorescence was used to detect the expressions of reactive oxygen species(ROS),superoxide dismutase(SOD),Caspase-3 and Caspase-9 in quadriceps femoris muscle tissue,fluorescence double staining method was used to detect the co-expression of ROS and Caspase-3 in quadriceps femoris tissue,Western blot was used to detect the expressions of apoptosis related proteins in quadriceps femoris tissue.Results Compared with the sham-operation group,the improved Lequesne MG score of the knee joint in the model group rats increased(P<0.05),the circumference of the thigh,wet weight of the quadriceps femoris,wet weight maintenance rate and wet weight ratio of the affected limb decreased(P<0.05),the arrangement of quadriceps femoris muscle fibers was disordered and loose,with some muscle fibers dissolved and necrotic,accompanied by a large amount of inflammatory exudate,an increase in lymphocytes,and an increase in cell apoptosis index(P<0.05),the expressions of ROS,Caspase-3 and Caspase-9 in quadriceps femoris tissue increased,while the expression of SOD decreased(P<0.05),the protein expressions of Bcl-2,Bcl-XL,Bax,Cytochrome C(CytC),Caspase-3 and Caspase-9 in quadriceps femoris tissue increased(P<0.05).Compared with the model group,the improved Lequesne MG scores of the knee joint in the celecoxib group and the meridian and tendon acupuncture group decreased(P<0.05),while thigh circumference,quadriceps femoris wet weight,wet weight maintenance rate,wet weight ratio increased(P<0.05),the structure of quadriceps femoris muscle fibers was normal,the muscle membrane was relatively intact,the apoptosis index decreased(P<0.05),the expressions of ROS,Caspase-3 and Caspase-9 in quadriceps femoris tissue decreased,while the expression of SOD increased(P<0.05),the protein expressions of Bcl-2,Bcl-XL,Bax,CytC,Caspase-3 and Caspase-9 in quadriceps femoris muscle tissue decreased(P<0.05),and the expression trend of ROS and Caspase-3 in fluorescent double staining was consistent.Conclusion Meridian and tendon acupuncture can reduce ROS in the quadriceps femoris tissue of KOA model rats,inhibit the expressions of mitochondrial apoptosis-related proteins,thereby improving skeletal muscle strength,and play a certain therapeutic role.

Objective To explore the mechanism of acupuncture protection of quadriceps muscle cells in knee osteoarthritis model rats based on Piezo1/YAP/Caspase3 axis.Methods 40 SPF grade Wistar rats were selected and adaptively fed for 7 days before being divided into three groups:sham surgery group,model group,western medicine group,and acupuncture group,with 10 rats in each group,according to a random control table.The model group,Western medicine group,and acupuncture group used the modified Hulth method to construct knee osteoarthritis models,while the sham surgery group only cut open the joint cavity and sutured it.After successful model replication,the sham surgery group was given physiological saline by gavage,the western medicine group was given celecoxib solution by gavage,and the acupuncture group was given acupuncture at the infrapatellar,crane top,and blood sea levels.Each group was intervened once a day for 14 consecutive days.During the treatment period,the rats continued to undergo treadmill training.After the intervention,the hematoxylin eosin staining method(HE)was used to detect the morphological changes of various rat quadriceps muscle tissues and articular cartilage;TUNEL method was used to detect apoptosis of quadriceps muscle cells,immunofluorescence method was used to detect the protein expression of Piezo1,YAP,and p-YAP in quadriceps muscle cells,Western blot method was used to detect the expression of anti apoptotic proteins CTGF,AREG,Gli2,AFP in quadriceps muscle tissue,as well as the protein expression levels of apoptosis related proteins Bcl-2,Bcl-xl,Bax,cytc,and Caspase3.Results Compared with the model group,the western medicine group and the acupuncture group had higher thigh circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight to body weight ratio(P<0.05).Compared with the western medicine group,the acupuncture group had higher thigh circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight to body weight ratio(P<0.05).Compared with the model group,the apoptosis index of the quadriceps muscle in the Western medicine group and acupuncture group rats was lower,and the apoptosis index of the quadriceps muscle in the acupuncture group was lower(P<0.05).Compared with the model group,the Western medicine group and acupuncture group showed higher expression of Piezo1 and p-YAP proteins in the quadriceps femoris muscle tissue,lower expression of YAP protein,higher expression of CTGF,AREG,Gli2,AFP proteins,higher expression of Bcl-2 and Bcl-xl proteins,and lower expression of Bax,cytc,and Caspase3 proteins(P<0.05).Compared with the Western medicine group,the acupuncture group showed higher expression of Piezo1 and p-YAP proteins in the quadriceps muscle tissue,lower expression of YAP protein,higher expression of CTGF,AREG,Gli2,AFP proteins,higher expression of Bcl-2 and Bcl-xl proteins,and lower expression of Bax,cytc,and Caspase3 proteins(P<0.05).Conclusion Acupuncture increases the expression of Piezo1 protein in the quadriceps femoris muscle of knee osteoarthritis model rats,promotes the phosphorylation of YAP into the nucleus,thereby promoting proliferation,anti apoptotic proteins CTGF,AREG,Gli2,and AFP protein expression,inhibiting Caspase3-dependent mitochondrial apoptosis,and protecting muscle cells.

Ceftazidime-avibactam （CAZ/AVI）is a novel β-lactam antibiotic with broad-spectrum antibacterial activity and good tolerability. However， the physiological and pathological differences in special populations [e.g. augmented renal clearance （ARC） patients， undergoing continuous renal replacement therapy （CRRT） patients， neonates and children， obese patients， undergoing extracorporeal membrane oxygenation （ECMO） patients， elderly patients and liver dysfunction patients] may affect the pharmacokinetic （PK） properties of CAZ/AVI， leading to treatment failure. At present， there is currently a lack of corresponding guidelines or consensus on dose adjustment of CAZ/AVI in special populations. This article summarizes the research on PK/ pharmacodynamic （PD） characteristics and dose adjustment of CAZ/AVI in special populations and recommends the following dosing regimens： for ARC patients， the recommended dose is 2.5 g， q8 h； for undergoing CRRT patients with infections caused by sensitive strains （i.e. MIC＜4 mg/L） and infections at sites where hydrophilic antibiotics distribute well， a dose of 1.25 g， q8 h may be used； for undergoing CRRT patients with less sensitive strains or sites with poorer drug distribution， a dose of 2.5 g， q8 h or continuous infusion may be considered； for children aged 6 months to ＜18 years with normal or mildly impaired renal function， a dose of 62.5 mg/kg， q8 h is infused for 2 h （maximum dose not exceeding 2.5 g per dose）； for infants aged 3～6 months with normal or mildly impaired renal function， a dose of 50 mg/kg， q8 h is infused for 2 h； for obese patients， the recommended dose is 2.5 g， q8 h， with therapeutic drug monitoring recommended；undergoing ECMO patients， elderly patients， and those with impaired liver function may also use the recommended dose of 179368757@qq.com 2.5 g， q8 h.