OBJECTIVES: To investigate the efficacy and safety of empagliflozin in patients with glycogen storage disease (GSD)-associated inflammatory bowel disease (IBD). METHODS: A cross-sectional study was conducted, enrolling 25 patients with GSD-associated IBD who received empagliflozin treatment. General data, details of empagliflozin use, and adverse events were collected. Clinical symptoms and biochemical parameters before and after empagliflozin therapy were compared. RESULTS: Twenty-five patients with GSD-associated IBD were included, with a median age at diagnosis of 0.7 years, and a mean age at initiation of empagliflozin therapy of (11 ± 6) years. The initial dose of empagliflozin was (0.30 ± 0.13) mg/(kg·d), with a maintenance dose of (0.40 ± 0.21) mg/(kg·d), and a treatment duration of (34 ± 6) months. Seventy-eight percent (18/23) of patients' parents reported that empagliflozin therapy reduced the frequency of infections and oral ulcers, and increased neutrophil counts. Clinically, the number of patients with anorexia decreased from 12 to 5 after treatment, and 30% showed improved appetite (P<0.05). The numbers of patients with diarrhea, mucus/bloody stools, perianal disease, and oral ulcers decreased from 19, 9, 11, and 21 before treatment to 7, 1, 0, and 10 after treatment, respectively (P<0.05). Laboratory findings showed that absolute neutrophil counts increased, while platelet counts, lactate, and uric acid levels decreased significantly after empagliflozin treatment (P<0.05). Adverse reactions occurred in 7 patients (28%) during empagliflozin treatment. Two cases occurred in the treatment initiation phase, presenting as hypotension or profuse sweating with dehydration, along with urinary tract infections (UTIs); empagliflozin was discontinued in both cases. During the maintenance phase, 3 cases of UTIs and 2 cases of hypoglycemia (one with profuse sweating) were reported. CONCLUSIONS Empagliflozin therapy can increase neutrophil counts, reduce the incidence of infections and oral ulcers, alleviate diarrhea and abdominal pain, improve appetite, and ameliorate platelet count, lactate, and uric acid levels in patients with GSD-associated IBD, demonstrating significant clinical benefit. UTIs, hypoglycemia, hypotension, profuse sweating, and dehydration may be potential adverse reactions associated with empagliflozin therapy.
Humans ; Benzhydryl Compounds/adverse effects* ; Male ; Female ; Glucosides/adverse effects* ; Inflammatory Bowel Diseases/etiology* ; Child ; Child, Preschool ; Cross-Sectional Studies ; Adolescent ; Glycogen Storage Disease/drug therapy* ; Infant

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

BACKGROUND:Traditional Chinese medicine has been proved to have a significant role in anti-osteoporosis,and the effectiveness and mechanism of Ligustri Lucidi Fructus and its the active ingredients against osteoporosis have gradually gained the attention of scholars.OBJECTIVE:To analyze and summarize the research progress of Ligustri Lucidi Fructus and its active ingredients against osteoporosis in vitro and in vivo.METHODS:We searched the relevant literature included in CNKI and PubMed databases using the search terms of"Osteoporosis,Bone marrow mesenchymal stem cells,Osteoblast,Osteoclast,Ligustri Lucidi Fructus,Signal path"in Chinese and English,respectively.According to the needs of the research,we established the corresponding criteria and screened the literature.A total of 82 papers were included in the final review.RESULTS AND CONCLUSION:(1)The active ingredients of Ligustri Lucidi Fructus that exert anti-osteoporotic effects in vitro and in vivo mainly involve the following:Salidroside activates the Wnt/β-catenin signaling pathway by inhibiting the expression of Sclerostin and Dickkopf-related protein 1.This activation process enhances the expression of phosphorylated low-density lipoprotein receptor-related protein 6 in ovariectomized rats and primary osteoblasts,while decreasing the expression of glycogen synthase kinase 3β.Further,it promotes the expression of β-catenin,runt-related transcription factor 2 and cellular myelocytomatosis oncogene in the nucleus,thereby promoting the bone formation capacity of osteoblasts.The advantage is that it acts directly on osteoblasts to promote bone formation,which provides a new strategy for the treatment of osteoporosis.(2)Olive bittersweet significantly increases bone mineral density and regulates bone metabolism by decreasing terminal interleukin-6 and alkaline phosphatase concentrations in Sprague-Dawley rats.In vitro experiments showed that olive bittersweet promotes the proliferation of osteoblasts and up-regulates the protein and mRNA expression of osteoprotegerin,while inhibiting the protein and mRNA expression of receptor activator of nuclear factor-κB ligand.This mechanism of action is closely related to the regulation of the balance of the osteoprotegerin/receptor activator of nuclear factor-κB ligand system,demonstrating the advantage of increasing bone mineral density and maintaining bone health by regulating factors related to bone metabolism,but there is no significant effect on Ca2+concentration,which may limit its use in some specific types of osteoporosis.(3)By decreasing the expression of phosphatidylinositol 3 kinase,reducing the phosphorylation of protein kinase B and the expression of osteoclast-specific marker protein c-Fos,pineconiferin effectively inhibits the activation of phosphatidylinositol 3 kinase/protein kinase B/c-Fos pathway in osteoclasts.This inhibition reduces the proliferation and maturation of osteoclasts,which can help to reduce bone resorption.The advantage of this inhibition is that it can directly target osteoclasts,which provides a new target for osteoporosis treatment.However,the specific regulatory mechanism of osteoclasts needs to be studied in depth,and its long-term effect and safety need to be further evaluated.(4)The active ingredients of Ligustri Lucidi Fructus have shown good therapeutic effects on osteoporosis,but their mechanism of action is complex,involving the interaction of multiple genes,proteins and signaling pathways.In the future,large-scale clinical trials need to be carried out to verify its effectiveness and safety,and the strategy of combining the active ingredients of Ligustri Lucidi Fructus with other drugs needs to be further explored in order to obtain better therapeutic effects.

Objective To investigate the impact of immunohistochemical detection of omentin-1(omentin-1),secreted phosphoprotein 1(SPP1),and mismatch repair(MMR)protein expression status on the clinicopathological characteristics and prognosis of endometrial cancer(EC),in order to provide references for disease assessment,prognosis evaluation,and the development of molecular targeted therapies.Methods A total of 159 patients diagnosed with EC who were admitted to our hospital between December 2019 and December 2021 were enrolled as the study group.Additionally,152 samples of normal endometrial tissue were collected from patients undergoing hysterectomy due to benign uterine diseases and served as the control group.The expression levels of omentin-1,SPP1,and MMR proteins in endometrial tissues were compared among the study group,the control group,and EC patients with different clinicopathological characteristics and prognostic outcomes.Spearman correlation analysis was performed to evaluate the correlations among these biomarkers in EC tissues.The influencing factors of EC prognosis were analyzed through multivariate logistic regression.Kaplan-Meier survival curves were constructed to assess the association between the expression of these proteins and patient prognosis.Results The positive expression rate of SPP1 and the MMR deletion rate in endometrial tissues of the study group were significantly higher than those in the control group(P<0.05),while the positive expression rate of omentin-1 in endometrial tissues was significantly lower than that in the control group(P<0.05).In patients with EC exhibiting myometrial invasion≥1/2,the proportion of omentin-1 negativity was lower compared to omentin-1 positivity(P<0.05).Among EC patients with poorly differentiated tumors,the rates of SPP1 positivity and MMR deficiency were significantly increased(P<0.05).Spearman correlation analysis revealed that omentin-1 expression was negatively correlated with both MMR protein deletion and SPP1 overexpres-sion(P<0.05),whereas MMR deficiency was positively correlated with SPP1 overexpression(P<0.05).In the poor prognosis group,the positive expression rate of SPP1 and the deletion rate of MMR were elevated,while omentin-1 expression was reduced in endometrial tissues(P<0.05).The results of multivariate logistic analysis showed that omentin-1 negative,SPP1 positive,and MMR deletion were risk factors for the prognosis of EC patients(P<0.05).Kaplan-Meier survival curves were constructed based on follow-up data(Figures 1-3),indicating that patients with omentin-1 negativity,SPP1 positivity,and MMR deficiency had significantly worse prognoses(P<0.05).Conclusions With the development and progression of the clinicopathological features of EC,abnormalities were observed in the immunohistochemical expression of omentin-1,SPP1,and MMR proteins.Specifically,omentin-1 negativity,SPP1 positivity,and MMR protein deletion were associated with a poorer prognosis in EC patients.

Anti-leucine-rich glioma-inactivated 1 protein (LGI1) antibody-associated encephalitis is an autoimmune encephalitis mediated by LGI1 antibodies, which can occur in both adults and children. Its common clinical manifestations include epileptic seizures, cognitive and psychiatric disorders; rare symptoms include sleep disorders and autonomic disorders; and its characteristic manifestations are faciobrachial dystonic seizures and refractory hyponatremia. Since anti-LGI1 antibody-associated encephalitis is relatively rare in clinical practice, this article reviews the disease in terms of etiology and pathogenesis, clinical manifestations, auxiliary examinations, diagnosis and differential diagnosis, treatment, recurrence and prognosis. It aims to improve clinicians′ understanding of this disease, provide references for its early diagnosis and treatment, and thereby improve patients′ prognosis.

Objective To investigate the association of endometrial thickness(EMT)with obstetric and neonatal outcomes of monoparous pregnancy in fresh cleavage embryos transfer.Methods A total of 1 845 patients of monoparous pregnancy after fresh cleavage embryos transfer cycles from Jan 2016 to Mar 2022 at Shanghai First Maternity and Infant Hospital,Tongji Universtiy were analyzed retrospectively.Patients were categorized into three groups by EMT on transferation day:≤8 mm(group A),8-14 mm(group B)and≥14 mm(group C).The primary outcomes were preterm birth(PTB),birth weight and birth weight z-score,small-for-gestation age,large-for-gestation age,very low birth weight,low birth weight and macrosomia.The second outcomes were pregnancy and perinatal complications.The relationship between EMT and adverse neonatal outcomes was estimated by Logistic regression analysis.Results The rate of ectopic pregnancy was increased significantly in group A.No significant differences were found among the three groups in gestation age,birth weight,birth weight z-score,PTB,small for gestation age,large for gestation age,low birth weight,very low birth weight and macrosomia.Compared with group B,the odds of adverse neonatal outcomes did not show significant differences before and after adjustment in both group A and group C by Logistic regression analysis.Conclusion Thinner EMT in fresh cleavage embryos transfer is associated with higher rate of ectopic pregnancy,while it is not independently associated with adverse perinatal outcomes.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.