Cognitive impairment （CI） is a clinical syndrome characterized by progressive decline in advanced cognitive functions such as memory， thinking， and judgment. Its etiology and pathogenesis are complex， and there is currently a lack of specific drug interventions. Metformin， as a first-line hypoglycemic drug for type 2 diabetes， not only lowers blood glucose levels but also improves CI. This article reviews and summarizes the pharmacological effects and mechanisms of metformin in improving Alzheimer’s disease， diabetes cognitive impairment， cognitive impairment after chemotherapy， in order to provide novel insights and approaches for the treatment of CI-related diseases. Studies have shown that the mechanism by which MET intervenes in CI mainly includes regulating β-amyloid protein and tau protein metabolism， reducing insulin resistance， inhibiting neuroinflammation， improving synaptic plasticity， improving mitochondrial dysfunction， regulating gut microbiota and lipid metabolism， etc. Future research needs to be conducted through interdisciplinary collaboration， fully integrating multiple omics data， and combining advanced technologies to further reveal their mechanisms of effect.

OBJECTIVE To investigate the efficacy and safety of the interleukin-1 （IL-1） receptor antagonist anakinra in the treatment of refractory adult onset Still’s disease （AOSD）， and provide more real-world evidence and practical experience for the treatment of AOSD with this drug. METHODS A retrospective analysis was conducted on the diagnosis and treatment process of a patient with AOSD complicated with dermatomyositis who received anakinra； systematically searched for relevant literature on the treatment of AOSD with anakinra in Chinese and English databases such as CNKI， PubMed， Medline， etc.， and conduct literature review on its efficacy and safety. RESULTS The patient in this case had poor treatment with multiple traditional drugs and was considered to have AOSD combined with dermatomyositis. After being admitted to the hospital and treated with a combination therapy of anakinra and glucocorticoids for several days， the patient’s clinical symptoms and inflammatory indicators significantly improved， and no serious adverse drug reactions occurred. Pharmacists designed specialized pharmaceutical monitoring pathways and conduct regular follow-up after discharge. After discharge， the patient took medication regularly， and the condition was maintained and relieved； during this period， there was redness and swelling at the injection site which resolved on its own without any other obvious discomfort. Literature review showed that anakinra could increase the response rate and remission rate of AOSD patients， and significantly reduce the dosage of glucocorticoids； adverse events were mainly injection site reactions， with a low overall risk of infection and good safety； however， there was a significant difference in the treatment course， and there was currently no unified plan. CONCLUSIONS Anakinra is an efficient and safe biological agent for treating AOSD， which can rapidly induce and maintain disease remission. For AOSD patients， clinical consideration may be given to using IL-1 antagonists to reduce glucocorticoid dependence， while strengthening long-term medication monitoring.

Cognitive impairment is a major public health challenge facing global aging societies， and currently lacks effective treatment measures. Herb pair， characterized by their rigorous compatibility and synergistic effects， demonstrate unique advantages in clinical practice. Acorus tatarinowii-Polygala tenuifolia is a classic herbal pair for treating cognitive impairment， widely utilized in various traditional Chinese medicine formulations， such as Kaixin san， Shenghui tang， and Yuanzhi san. This article summarizes the pharmacological mechanisms of A. tatarinowii， P. tenuifolia and their compatible compound prescriptions in ameliorating cognitive impairment. It is found that they can exert effects in ameliorating cognitive impairment through mechanisms such as reducing amyloid β-protein deposition and inhibiting excessive phosphorylation of Tau protein， suppressing inflammatory responses， alleviating oxidative stress， protecting neurons and regulating neurotransmitters， modulating the structure and function of the blood- brain barrier， and regulating autophagy. Subsequently， in-depth analysis can be conducted on the active ingredients of A. tatarinowii- P. tenuifolia herb pair that ameliorate cognitive impairment， along with the addition of relevant clinical trials for verification. This will provide theoretical foundations and research approaches for the treatment of cognitive impairment using traditional Chinese medicine.

Nerve block is a technique for anesthesia and pain management, which is realized by blocking nerve conduction in a specific nerve area with local anesthetic drugs. Compared with general anesthesia, nerve block has many advantages, which can provide local and selective analgesic effect, and meanwhile reduce complications and drug side effects related to general anesthesia. Dexmedetomidine is a type of α₂ adrenergic receptor agonist, and as a potential adjuvant, dexmedetomidine has been widely applied in nerve block. Dexmedetomidine has sedative, analgesic and anti-anxiety effects, and can be used in combination with local anesthetics to enhance the effect of nerve block. In this paper, the clinical effects of dexmedetomidine as an adjuvant of nerve block in various parts are reviewed, and application in maxillofacial nerve block and stellate ganglion block was added in order to provide reference for nerve block anesthesia and analgesia.

The quality of recovery after surgery not only affects patient's satisfaction degree, but also affects patient's prognosis. With the goal of promoting early recovery, the potential advantages of amide local anesthetic lidocaine in perioperative intravenous application have attracted much attention. Intravenous infusion of lidocaine has many benefits, such as analgesia, anti-inflammatory, anti-tumor, and organ protection, and can effectively improve patient's prognosis. This study reviewed the current status of lidocaine in clinical intravenous application, explored its advantages in promoting patient's recovery, and briefly described the relevant mechanisms and safety of its application in the perioperative period.

We previously identified a unique nucleus, the cerebrospinal fluid (CSF)-contacting nucleus. This study aims to understand its gene architecture and preliminarily suggest its functions. The results showed that there were about 19,666 genes in this nucleus, of which 913 were distinct from the dorsal raphe nucleus (non-CSF contacting). The top 40 highly-expressed genes are mainly related to energy metabolism, protein synthesis, transport, secretion, and hydrolysis. The main neurotransmitter is 5-HT. The receptors of 5-HT and GABA are abundant. The channels for Cl^-, Na⁺, K⁺, and Ca²⁺ are routinely expressed. The signaling molecules associated with the CaMK, JAK, and MAPK pathways were identified accurately. In particular, the channels of transient receptor potential associated with nociceptors and the solute carrier superfamily members associated with cell membrane transport were significantly expressed. The relationship between the main genes of the nucleus and life activities is preliminarily verified.
Rats ; Animals ; Rats, Sprague-Dawley ; Serotonin/metabolism* ; Signal Transduction ; Cerebrospinal Fluid/metabolism*

Objective:To investigate the effect of pioglitazone on white matter injury after cerebral ischemia-reperfusion in mice and its mechanism.Methods:Forty-two young male C57BL/6J mice were randomly divided into sham operation group, model group, and pioglitazone group ( n=14 in each group). The model of cerebral ischemia-reperfusion was induced by transient middle cerebral artery occlusion with suture-occluded method. On the 3 rd and 7 th day after the establishment of the model, the neural function was assessed by the adhesive removal test. The mice were killed on the 7 th day after the establishment of the model. HE staining was used to detect the extent of cerebral infarction. Immunofluorescence staining and Western blot analysis were used to detect the degree of white matter damage and the changes of microglia phenotype. Results:On the 7 th day after cerebral ischemia-reperfusion, the adhesive removal time in the PGZ group was significantly shortened compared with the model group ( P<0.05), the percentage of cerebral infarction volume was significantly reduced ( P<0.05), the ratio of MBP/NF200 fluorescence intensity in the cortical and striatal areas was significantly increased (all P<0.05), and the number of CD16 +/Iba1 + microglia was significantly decreased ( P<0.01), while the number of CD206 +/Iba1 + microglia tended to increase, but there was no statistical difference. Conclusion:Pioglitazone may reduce the degree of white matter injury and nerve function damage in mice with cerebral ischemia-reperfusion, and its mechanism may be associated with regulating the transformation of microglia from M1 type to M2 type.

Objective:To investigate the effect of irradiation on the expression of miR-150-5p and miR-23a-3p in human peripheral blood serum by collecting peripheral blood of tumor patients before and after radiotherapy, so as to provide scientific basis for finding radiation biomarkers.Methods:A total of 63 tumor patients treated with radiotherapy from October 2021 to March 2022 were enrolled in this study. The relative expression levels of miR-150-5p and miR-23a-3p in peripheral blood serum in these patients were detected using the real-time fluorescence quantitative PCR (qPCR) before and after radiotherapy. The differential changes in the expression levels of the two miRNAs in the peripheral blood serum of the patients before and after radiotherapy were compared, and their relationships with factors such as cancer types were analyzed.Results:The relative expression levels of miR-150-5p and miR-23a-3p in peripheral blood serum of the patients after radiotherapy were significantly lower than those before radiotherapy ( t = 4.97, Z = -2.77, P < 0.05). Among different cancer types, the relative expression level of miR-150-5p in the patients with breast cancer, esophageal cancer, or other digestive tract cancer decreased after radiotherapy ( t = 3.47, 2.47, 2.87, P < 0.05), and the relative expression level of miR-23a-3p in the patients with digestive tract cancer decreased after radiotherapy ( Z = -1.99, P < 0.05). The changes in the expression level of miR-150-5p before and after radiotherapy were not affected by gender, age, chemotherapy, and cancer type ( P > 0.05). By contrast, the changes in the expression level of miR-23a-3p before and after radiotherapy were significantly affected by gender, age, and chemotherapy ( t=2.04, -3.34, -2.29, P<0.05). Conclusions:The expression of miR-150-5p in the serum of tumor patients may be affected by radiotherapy, which has the potential to be used as a biological indicator of radiation.

Objective:To explore the associations of urinary retinol binding protein (RBP) and β 2-microglobulin (β 2-MG) with urinary albumin to creatinine ratio (UACR) and renal function in hospitalized patients with type 2 diabetes mellitus (T2DM). Methods:A total of 1 030 Chinese patients with T2DM were included in this study. The subjects were divided into the UACR normal group (<30 mg/g), microalbuminuria group (30-300 mg/g) and macroalbuminuria group (>300 mg/g). Patients with normal UACR were further divided into two groups according to the estimated glomerular filtration rate (eGFR): the eGFR low group (<90 ml·min -1·1.73m -2) and the normal eGFR group (≥90 ml·min -1·1.73m -2). Urine RBP and β 2-MG levels among the groups were compared. Multiple linear regression analyses were applied to evaluate risk factors of urine RBP and β 2-MG. Results:In all patients ( n=1 030), urine RBP and β 2-MG increased gradually with the increase of UACR across the three groups, the proportions of abnormal urine RBP (>0.7 mg/L) and β 2-MG (>370 μg/L) in these groups were 3.8%, 8.5%, 39.0% ( P<0.001), and 12.9%, 26.7%, 46.8% ( P<0.001), respectively. In the UACR normal group ( n=788), 12.2% of the patients were with eGFR<90 ml·min -1·1.73m -2. The proportion of abnormal β 2-MG (>370 μg/L) was higher in the eGFR low group than that in the eGFR normal group (29.2% vs. 10.7%, P<0.001). Multivariate linear stepwise regression analyses were performed using natural logarithm of urine RBP or β 2-MG as dependent variable, and showed that urine RBP was independently associated with UACR ( β=0.0005, P<0.001), serum creatinine ( β=0.006, P<0.001) and glycosylated hemoglobin A1c ( β=0.050, P=0.001), and β 2-MG was independently correlated with UACR ( β=0.000 4, P<0.001), serum creatinine ( β=0.011, P<0.001), systolic blood pressure ( β=0.005, P=0.031) and fasting blood-glucose ( β=0.027, P=0.046). Conclusions:Urine RBP and β 2-MG are positively associated with high UACR and impaired renal function in T2DM patients, and these changes could occur before UACR and eGFR turned out to be abnormal. It is recommended that urine RBP and β 2-MG be detected as early as possible to identify diabetic kidney disease in patients with normal UACR and eGFR.

Objective:To investigate the imaging and clinical characteristics of posttransplantation lymphoproliferative disorders (PTLD) after liver transplantation in children.Methods:From February 2017 to November 2020, the imaging and clinical data of 17 children with PTLD after liver transplantation confirmed by pathology or clinical diagnosis were retrospectively analyzed in Shanghai Children′s Medical Center, School of Medicine, Shanghai Jiao Tong University. The site, range, density/signal/echo of the lesions were observed.Results:The mean age at transplantation was 8 (7, 11) months, and 14 patients were younger than 1 year old. The interval between liver transplantation and PTLD diagnosis was 22 (10, 34) months, ranging from 3 to 54 months. The interval was less than 1 year in 6 patients (early onset) and equal or greater than 1 year in 11 patients (late onset). Fifteen patients had Epstein-Barr virus infection. Among the 12 pathologically confirmed PTLD cases, 8 cases were diffuse large B-cell lymphoma, 3 cases were Burkitt lymphoma, and 1 case was reactive plasma cell hyperplasia. Among the 17 children with PTLD, 8 cases demonstrated involvement of lymph nodes and 16 cases had extranodal involvement. The latter included 15 cases of abdominal involvement. Abdominal sites involved included small intestine in 14 cases, colon in 7 cases, mesentery in 4 cases, kidney in 3 cases, liver in 2 cases, abdominal lymph nodes in 2 cases, peritoneum in 1 case, and stomach in 1 case. The sites of extra-abdominal involvement included lymph nodes in 7 cases, lung in 3 cases, skull in 1 case, brain in 1 case, pleura in 1 case, chest wall in 1 case, and nasopharynx in 1 case. The most common abdominal imaging abnormalities were thickening of the intestinal wall, eccentric mass and dilation of the lumen. Both small intestines and colons could be involved, and the former more commonly. Multiple masses were found in patients with liver and kidney involvement. The most common imaging manifestation of PTLD outside the abdomen was lymph node enlargement, which was found in 7 cases, and the most common was in the neck. The manifestation was shorter diameter of lymph nodes>10 mm, uniform density and signal, with mild enhancement.Conclusions:PTLD can occur months to years after liver transplantation in children, which can affect many parts of the whole body. Extranodal lesions are more than intranodal lesions. Abdominal involvement is most common in PTLD, and the infection rate of EB virus is high. Combined with medical history, EB virus infection status and imaging examination are helpful for early diagnosis.