BACKGROUND:Prolyl hydroxylase domain 2(PHD2)inhibitors can regulate bone metabolism and relieve osteoporosis in ovariectomized rats.cpd17 is a small molecule oral PHD2 inhibitor newly developed by China Pharmaceutical University.It is effective in the treatment of renal anemia with few side effects,but its effect on bone formation and bone resorption is still unclear. OBJECTIVE:To investigate the effects of cpd17 on mouse osteogenic precursor cells. METHODS:Osteogenic precursor cells were treated with cpd17.Alkaline phosphatase activity and extracellular matrix mineralization were measured,and the expression levels of osteogenesis-and osteoclastogenesis-related markers,as well as PHD2 and hypoxia-inducible factor 1α,were detected.After inhibition of the hypoxia-inducible factor 1α pathway using LW6(a hypoxia-inducible factor 1α pathway inhibitor),alkaline phosphatase activity and extracellular matrix mineralization were detected again,as well as the expression levels of osteogenesis-and osteoclastogenesis-related markers,PHD2 and hypoxia-inducible factor 1α. RESULTS AND CONCLUSION:cpd17 significantly enhanced alkaline phosphatase activity and extracellular matrix mineralization,up-regulated the expression of osteogenesis-related markers,down-regulated the expression of osteoclastogenesis-related markers,up-regulated the expression of hypoxia-inducible factor 1α,down-regulate the expression of PHD2.However,cpd17's effects were significantly attenuated by LW6.To conclude,the PHD2 inhibitor cpd17 promotes osteogenic differentiation and inhibits osteoclastic differentiation through activation of the hypoxia-inducible factor 1α signaling pathway.

ObjectiveTo investigate the intervention effects of Suanzaoren Tang on depression model rats induced by isolation combined with chronic unpredictable mild stress （CUMS）， and to examine its influence on the c-Jun N-terminal kinase （JNK）/proto-oncogene protein （c-Myc）/tumor suppressor protein 53 （p53） signaling pathway， thereby revealing its potential functional mechanism. MethodsA total of 72 male SD rats were randomly divided into six groups using a strict random number table： blank group， model group， fluoxetine group （3.6 mg·kg^-1）， and high-， medium-， and low-dose Suanzaoren Tang groups （10， 5， 2.5 g·kg^-1），with 12 rats in each group. A depression model was established using isolation combined with CUMS. Fluoxetine and different doses of Suanzaoren Tang were administered continuously for 28 days. Behavioral indicators such as sucrose water consumption and open field test scores were recorded. Western blot and immunohistochemistry （IHC） were employed to analyze the expression of key proteins in the JNK/c-Myc/p53 signaling pathway， and the terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was used to evaluate the number of apoptotic cells in the hippocampus. ResultsCompared with the blank group， the model group exhibited a significantly reduced sucrose preference index （P<0.01）， a lower total score of horizontal and vertical movements in the open field test （P<0.01）， significantly increased expression of JNK， c-Myc， and p53 proteins in the hippocampus （P<0.01）， and a higher number of TUNEL-positive cells in the hippocampus （P<0.01）. Compared with the model group， the sucrose preference index and the total score of horizontal and vertical movements in the open field test significantly increased in the high- and medium-dose Suanzaoren Tang groups and the fluoxetine group （P<0.05， P<0.01）. The expression of JNK， c-Myc， and p53 proteins significantly decreased in all Suanzaoren Tang groups （high， medium， and low doses） and the fluoxetine group （P<0.05， P<0.01）. The number of TUNEL-positive cells in the hippocampus also significantly decreased in these groups （P<0.01）. ConclusionSuanzaoren Tang can regulate the expression of JNK/c-Myc/p53 proteins in the hippocampus of depression model rats， and its antidepressant mechanism may be related to its protective effect on hippocampal neurons.

Osteonecrosis of the femoral head(ONFH)is a disabling orthopedic disease,pathologically characterized by progressive collapse of the femoral head accompanied by destruction of the trabecular and articular cartilage structures,leading to hip joint pain and progressive functional impairment.Bone marrow mesenchymal stem cell-derived extracellular vesicles(BMSC-EVs)show great promise in tissue repair and regeneration,with low immunogenicity and tumorigenicity,and play roles in osteogenesis,angiogenesis,and immunomodulation.This review summarizes the therapeutic effects and underlying mechanisms of BMSC-EVs in ONFH,providing a theoretical basis for its treatment.

Objective To observe the efficacy of percutaneous vertebroplasty(PVP)combined with microwave ablation(MWA)for treating vertebral compression fractures(VCF)caused by metastatic cancer.Methods Totally 112 patients with VCF caused by metastatic cancer were retrospectively enrolled,including 77 cases(105 vertebrae)underwent MWA+PVP(group A)and 35 cases(68 vertebrae)who underwent PVP alone(group B).The success rates of the treatments were recorded,and complications were observed.Visual analogue scale(VAS)score of pain,daily morphine consumption(DMC)and Oswestry disability index(ODI)of patients were compared within and between groups after treatments,and local tumor recurrence rates after treatment were observed.Results The success rates of MWA and PVP were both 100%.After treatments,bone cement leakage occurred in 12 cases(12/77,15.58%)in group A and 19 cases(19/35,54.29%)in group B,in group A was lower than in group B(P＜0.001).No other complications occurred.One week and 1,3 and 6 months after treatments,VAS scores of pain,DMC and ODI in group A and B were all lower than those before treatments(all P＜0.001).Three and 6 months after treatments,VAS scores of pain in group A were lower than those in group B(both P＜0.01),while 6 months after treatments,DMC and ODI in group A were lower than those in group B(both P＜0.01).No significant difference of VAS scores of pain,DMC nor ODI was found between groups at the other time points(all P＞0.05).Six months after treatments,local tumor recurrence rate in lesions in group A(17.14%,18/105)was significantly lower than that in group B(32.35%,22/68)(P=0.020).Conclusion For treating VCF caused by metastatic cancer,PVP combined with MWA could reduce incidence of complications,prolong pain relief time and bring better short-term local tumor control effect.

Glucagon-like peptide-1 receptor agonists (GLP-1RA) have been widely used in the treatment of type 2 diabetes mellitus (T2DM). However, the acceleration of heart rate caused by GLP-1RA should not be ignored. In the general population and patients with diabetes, increased heart rate has an independent correlation with the incidence and mortality of cardiovascular diseases. In general, the long-acting GLP-1RA seem to exert a greater effect in increasing heart rate, and the effect is dose-dependent and negatively correlated with baseline heart rate. The increase in heart rate caused by GLP-1RA may be related to enhanced sympathetic nervous activity, reflex tachycardia as a response to vasodilation, etc. It is advisable to closely monitor the increased heart rate induced by GLP-1RA in clinical practice, especially in patients with high-risk factors for cardiovascular disease. In case of elevated heart rate, the management begins with immediate discontinuation of the GLP-1RA and symptomatic intervention should be given if necessary.

Objective:To explore the clinical features of nivolumab-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).Methods:Relevant databases at home and abroad (as of December 31, 2023) were searched to collect case reports of nivolumab-induced SJS/TEN, and the demographic characteristics, nivolumab application, combination drugs, clinical manifestations, intervention measures, and outcomes were extracted and analyzed descriptively and statistically.Results:A total of 27 case reports were included and 29 patients were enrolled in the study, including 18 males and 11 females. The age ranged from 45 to 86 years, with an average age of 67 years. The primary diseases were mainly melanoma, stomach cancer, and lung cancer. Twelve patients had records of nivolumab administration, and the dosage was within the recommended range in the labels; 13 patients had records of combination drugs, mainly other antineoplastic drugs, hypoglycemic drugs, antihypertensive drugs, lipid-regulating drugs, etc. The time from using nivolumab to the diagnosis of SJS/TEN was 7 d to 3 years, and 20 patients were <8 weeks. The clinical manifestations were mainly diffuse erythema, flaky skin peeling and erosion, mucosal involvement, etc. Sixteen patients had skin biopsy records, all of which met the histopathological characteristics of SJS/TEN. After the diagnosis of SJS/TEN, 17 patients discontinued nivolumab and received symptomatic treatments, of which 15 patients had improved skin symptoms, one patient had worsened skin symptoms, and one patient had no record of skin outcome; 12 patients had no record of whether or not discontinuing nivolumab, of which 8 patients had improved skin symptoms, 2 patients had worsened skin symptoms, one patient had no record of skin outcome, and one had no record of prognosis. One patient rechallenged nivolumab, severe SJS/TEN recurred. Thirteen of 29 patients died. Of them, 1 died due to cardiac arrest, 4 due to worsened skin rash, and 8 due to primary disease progression.Conclusions:SJS/TEN caused by nivolumab mostly occurs within 8 weeks of treatment, and the clinical manifestations were similar to those caused by other drugs. The mortality rate of nivolumab-induced SJS/TEN is high, and skin rash could be improved after withdrawal of nivolumab and symptomatic treatments.

The clinical diagnosis and treatment of urinary tract infection has long faced the challenges of insufficient standardization of diagnosis and treatment pathways,irrational use of antimicrobial drugs and high recurrence rate.How to optimize the hierarchical diagnosis and treatment pathway of urinary tract infection,standardize the use of antimicrobial drugs,and reduce the recurrence rate have always been the focus of clinical attention.There is significant heterogeneity in the existing diagnostic criteria for urinary tract infection,which seriously affects the comparability and evidence integration of clinical and research studies.In order to solve the above problems,a consensus on global multidisciplinary diagnostic criteria for urinary tract infection has been formed by international multidisciplinary experts after three rounds of Delphi method.Breaking through the traditional classification framework,the consensus innovatively established a four-dimensional quantitative scoring system including local symptoms and signs,systemic inflammatory response,quantitative analysis of pyuria and urine culture results,and established a hierarchical standard for stepwise urinary tract diagnosis according to the scoring threshold.Based on the key citations related to the consensus,this paper interprets in detail the basis for the selection of core indicators and the establishment of thresholds for the diagnosis of urinary tract infection in the consensus,and focuses on the key issues and implementation paths of the consensus in localization practice.This consensus provides a unified standard for standardizing the clinical diagnosis and treatment of urinary tract infection,improving the homogeneity of clinical research through standardized diagnostic processes,and promoting the standardization of UTI drug research and development and the rational use of antibiotics and precision.

Osteonecrosis of the femoral head(ONFH)is a disabling orthopedic disease,pathologically characterized by progressive collapse of the femoral head accompanied by destruction of the trabecular and articular cartilage structures,leading to hip joint pain and progressive functional impairment.Bone marrow mesenchymal stem cell-derived extracellular vesicles(BMSC-EVs)show great promise in tissue repair and regeneration,with low immunogenicity and tumorigenicity,and play roles in osteogenesis,angiogenesis,and immunomodulation.This review summarizes the therapeutic effects and underlying mechanisms of BMSC-EVs in ONFH,providing a theoretical basis for its treatment.

The clinical diagnosis and treatment of urinary tract infection has long faced the challenges of insufficient standardization of diagnosis and treatment pathways,irrational use of antimicrobial drugs and high recurrence rate.How to optimize the hierarchical diagnosis and treatment pathway of urinary tract infection,standardize the use of antimicrobial drugs,and reduce the recurrence rate have always been the focus of clinical attention.There is significant heterogeneity in the existing diagnostic criteria for urinary tract infection,which seriously affects the comparability and evidence integration of clinical and research studies.In order to solve the above problems,a consensus on global multidisciplinary diagnostic criteria for urinary tract infection has been formed by international multidisciplinary experts after three rounds of Delphi method.Breaking through the traditional classification framework,the consensus innovatively established a four-dimensional quantitative scoring system including local symptoms and signs,systemic inflammatory response,quantitative analysis of pyuria and urine culture results,and established a hierarchical standard for stepwise urinary tract diagnosis according to the scoring threshold.Based on the key citations related to the consensus,this paper interprets in detail the basis for the selection of core indicators and the establishment of thresholds for the diagnosis of urinary tract infection in the consensus,and focuses on the key issues and implementation paths of the consensus in localization practice.This consensus provides a unified standard for standardizing the clinical diagnosis and treatment of urinary tract infection,improving the homogeneity of clinical research through standardized diagnostic processes,and promoting the standardization of UTI drug research and development and the rational use of antibiotics and precision.

Objective To observe the efficacy of percutaneous vertebroplasty(PVP)combined with microwave ablation(MWA)for treating vertebral compression fractures(VCF)caused by metastatic cancer.Methods Totally 112 patients with VCF caused by metastatic cancer were retrospectively enrolled,including 77 cases(105 vertebrae)underwent MWA+PVP(group A)and 35 cases(68 vertebrae)who underwent PVP alone(group B).The success rates of the treatments were recorded,and complications were observed.Visual analogue scale(VAS)score of pain,daily morphine consumption(DMC)and Oswestry disability index(ODI)of patients were compared within and between groups after treatments,and local tumor recurrence rates after treatment were observed.Results The success rates of MWA and PVP were both 100%.After treatments,bone cement leakage occurred in 12 cases(12/77,15.58%)in group A and 19 cases(19/35,54.29%)in group B,in group A was lower than in group B(P＜0.001).No other complications occurred.One week and 1,3 and 6 months after treatments,VAS scores of pain,DMC and ODI in group A and B were all lower than those before treatments(all P＜0.001).Three and 6 months after treatments,VAS scores of pain in group A were lower than those in group B(both P＜0.01),while 6 months after treatments,DMC and ODI in group A were lower than those in group B(both P＜0.01).No significant difference of VAS scores of pain,DMC nor ODI was found between groups at the other time points(all P＞0.05).Six months after treatments,local tumor recurrence rate in lesions in group A(17.14%,18/105)was significantly lower than that in group B(32.35%,22/68)(P=0.020).Conclusion For treating VCF caused by metastatic cancer,PVP combined with MWA could reduce incidence of complications,prolong pain relief time and bring better short-term local tumor control effect.