Restless legs syndrome （RLS） is a common neurological sensory-motor disorder， and the diagnosis of RLS mainly rely on the subjective clinical symptoms described by the patient， with a lack of specific auxiliary examinations or biomarkers. The diagnosis of this disease is still challenging for atypical cases. Various other diseases may have similar clinical symptoms as RLS， such as leg discomfort， leg pain and abnormal leg movement. This article summarizes the RLS mimics that might be confused with RLS symptoms， including the neurogenic， vascular， and musculoskeletal factors that might cause leg discomfort and pain， as well as the differential diagnosis of sleep-related movement disorders with symptoms overlapped with RLS， so as to help clinicians recognize RLS phenotype and provide a reference for the diagnosis of diseases that might be confused with RLS.

Cerebral small vessel disease （CSVD） is a spectrum of pathological conditions affecting intracranial small blood vessels and is associated with a variety of clinical manifestations， including cognitive impairment， gait abnormalities， and sleep disorders. In recent years， the association between CSVD and sleep disorders has attracted increasing attention. This article reviews the association of CSVD with various sleep disorders such as obstructive/central sleep apnea hypoventilation syndrome， restless legs syndrome， and insomnia， analyzes the mechanisms by which sleep disorders cause CSVD， and proposes potential directions for future research.

Severe acute pancreatitis(SAP)is a critical condition in general surgery settings,characterized by high mortality and poor prognosis.On February 28,2024,the Department of Hepatobiliary Surgery at the First Affiliated Hospital of Harbin Medical University admitted a 36-year-old male patient.The patient presented with"upper abdominal pain accompanied by fever for three months and jaundice of the skin and sclera for one week."Physical examination revealed 11 puncture tubes,and a palpable mass measuring 3 cm × 5 cm in the upper abdomen.Enhanced CT and magnetic resonance cholangiopancreatography indicated acute pancreatitis.The patient was diagnosed with"SAP,infectious pancreatic necrosis,and biliary stenosis."He had severe abdominal infection and complex postoperative complications,making treatment challenging.Consequently,a multidisciplinary team(MDT)consultation was initiated.After three rounds of MDT consulfation and freating,the patient ultimately recovered successfully and was discharged.This article reviews the MDT treatment process for this patient and summarizes the characteristics of this condition based on relevant literature to provide insights and experience for clinical practice.

OBJECTIVE To compare the similarities and differences of the two methods in analyzing the use of opioids in third grade class A medical institutions and provide a reference for the management of opioids in medical institutions. METHODS Two methods， Defined Daily Dose （DDD） and Oral Morphine Equivalent （OME）， were used to count the opioid prescription data of five comprehensive medical institutions of third grade class A （named H1-H5） in Shanxi province in 2020， calculate consumption sum of opioid， annual per capita consumption sum， patient cost burden and drug consumption sum ratio， compare the index results presented by the two analysis methods， and explore the application scenarios of the advantages of each of the two evaluation methods. RESULTS The ranking of consumption sum of opioid and patient cost burden calculated by the two methods was the same in the five sample medical institutions， but the ranking of per capita consumption sum was different. Taking the 5 medical institutions as a whole， the top 4 rankings of consumption sum ratio for each species of opioid compared by both methods were the same， i. e. remifentanil＞sufentanil＞oxycodone＞morphine. The ratio of remifentanil was close to 50%. When comparing the ranking of consumption sum ratio in each medical institution， the ranking calculated by the two methods was different for those medical institutions except for H1 medical institutions. The consumption sum ratio of fentanyl calculated by DDD method was significantly higher than that of OME method； whereas consumption sum ratio of remifentanil calculated by OME method was significantly higher than that of DDD method. Perioperative patients had the highest consumption sum ratio， about 50%. The consumption sum ratio of critically ill patients in H3 jwsydey@163.com medical institutions and inpatient patients with cancer pain and other patients in H5 medical institutions calculated by DDD method was significantly higher than that by OME method. There were differences in the order of cost burden of different types of patients calculated by two methods. CONCLUSIONS DDD method can accurately reflect the dosage of opioid drugs and facilitate the monitoring and management of the dosage； OME method can more reflect the analgesic effect and compare the cost burden of patients.

Objective: To study the non/hypo-response to hepatitis B vaccination in HIV-infected patients, identify the influencing factors and provide evidence for the development of hepatitis B prevention and control strategies and measures for special population. Methods: On the basis of the randomized controlled trial of 20 µg hepatitis B vaccine immunization at 0-1-6 month, 0-1-2-6 month and 60 µg hepatitis B vaccine immunization at 0-1-2-6 month, the HIV-infected patients who completed one-month follow-up after the full course vaccination were selected as study subjects. Quantification of antibody to hepatitis B surface antigen (anti-HBs) in serum samples was performed by using chemiluminescent microparticle immunoassay (CMIA) and demographic characteristics, disease history, HIV infection and treatment status of the study subjects were collected. Statistical analysis was conducted by χ² test, t test, unconditional logistic regression and interaction analyses. Results: The non/hypo-response rates to hepatitis B vaccination were 34.65% (35/101), 24.49% (24/98) and 10.99% (10/91) in 20 µg group at 0-1-6 month or 0-1-2-6 month and 60 µg group at 0-1-2-6 month (P<0.001), respectively. Logistic regression analysis showed that after controlling for confounding factors, the risk for non/hypo-response was 0.22 times higher in HIV-infected patients receiving 60 µg hepatitis B vaccine at 0-1-2-6 month than in patients receiving 20 µg hepatitis B vaccine at 0-1-6 month (95%CI: 0.10-0.50), the risk for non/hypo-response was higher in men than in women (OR=3.65, 95%CI: 1.88-7.07), and the risk for non/hypo-response was 2.64 times higher in those without hepatitis B vaccination history than in those with hepatitis B vaccination history (95%CI: 1.10-6.32). Moreover, there were multiplicative interactions between immunization schedule and gender (OR=2.49, 95%CI: 1.24-5.00). Conclusion: The non/hypo-response rate to hepatitis B vaccination was significantly lower in HIV-infected patients receiving 60 µg hepatitis B vaccine at 0-1-2-6 month than in those receiving 20 µg hepatitis B vaccine at 0-1-6 month and 0-1-2-6 month. Gender, vaccination schedule and history of hepatitis B vaccination were the influencing factors of the non/hypo-response to hepatitis B vaccination. There was a multiplicative interaction between vaccination schedule and gender, and men receiving 20 µg hepatitis B vaccines had a higher risk for non/hypo-response to hepatitis B vaccination.
Female ; Follow-Up Studies ; HIV Infections/immunology* ; Hepatitis B/prevention & control* ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines/administration & dosage* ; Humans ; Immunization Schedule ; Male

Gene editing technology has been a hotspot in the field of biotechnology. CRISPR/Cas systems are efficient gene editing tools because of its specificity, simplicity and flexibility, these features enabled the rapid application of CRISPR/Cas systems in a variety of organisms. Moreover, the combination of transcriptional activator with dead Cas protein can achieve specific regulation of gene expression at the transcription level, which has made important contributions to the development of biotechnology in medical and agriculture. Overexpression of foreign genes is a common method to verify gene function and regulation. However, due to the limitation of vector capacity, it is difficult to achieve overexpression of multiple genes. CRISPR/Cas9 activation system can regulate the expression of multiple genes under the guidance of different guide RNAs to verify gene functions at the regulatory level. This review summarizes the composition of the CRISPR/Cas9 activation system and different activation strategies, and summarizes solutions for excessive activation. It may facilitate the application of CRISPR/Cas9 activation system in genetic improvement of cotton and herbicide resistance research.
Biotechnology ; CRISPR-Cas Systems/genetics* ; Gene Editing ; Phenotype ; RNA, Guide, Kinetoplastida/metabolism*

Early distinction of bipolar disorder (BD) from major depressive disorder (MDD) is difficult since no tools are available to estimate the risk of BD. In this study, we aimed to develop and validate a model of oxidative stress injury for predicting BD. Data were collected from 1252 BD and 1359 MDD patients, including 64 MDD patients identified as converting to BD from 2009 through 2018. 30 variables from a randomly-selected subsample of 1827 (70%) patients were used to develop the model, including age, sex, oxidative stress markers (uric acid, bilirubin, albumin, and prealbumin), sex hormones, cytokines, thyroid and liver function, and glycolipid metabolism. Univariate analyses and the Least Absolute Shrinkage and Selection Operator were applied for data dimension reduction and variable selection. Multivariable logistic regression was used to construct a model for predicting bipolar disorder by oxidative stress biomarkers (BIOS) on a nomogram. Internal validation was assessed in the remaining 784 patients (30%), and independent external validation was done with data from 3797 matched patients from five other hospitals in China. 10 predictors, mainly oxidative stress markers, were shown on the nomogram. The BIOS model showed good discrimination in the training sample, with an AUC of 75.1% (95% CI: 72.9%-77.3%), sensitivity of 0.66, and specificity of 0.73. The discrimination was good both in internal validation (AUC 72.1%, 68.6%-75.6%) and external validation (AUC 65.7%, 63.9%-67.5%). In this study, we developed a nomogram centered on oxidative stress injury, which could help in the individualized prediction of BD. For better real-world practice, a set of measurements, especially on oxidative stress markers, should be emphasized using big data in psychiatry.
Biomarkers/metabolism* ; Bipolar Disorder/metabolism* ; Depressive Disorder, Major/diagnosis* ; Early Diagnosis ; Humans ; Oxidative Stress

To analyze the main factors influencing the ethical review work of municipal hospitals in Shanxi Province by investigating the current situation of the construction and operation of ethics committees, and to put forward reasonable suggestions for improving the work of ethics committees. Questionnaire surveys and interviews were used to investigate the composition of ethics committees, systems and standard operating procedures, personnel training, review project methods, time limits, etc. of 24 hospitals at municipal levels in Shanxi Province. The establishment and system of ethics committees in tertiary hospitals at prefecture and city level were basically reasonable, and they could actively play the role of ethics committees. At present, most hospitals do not pay enough attention to the work of ethics committees, lack of full-time staff and systematic training, resulting in insufficient ethics review capabilities. The construction of the ethics committee of the second-level hospital is a mere formality, and no substantive work has been carried out. It is recommended to strengthen the supervision, increase the training of ethics committees and researchers, improve the information management of ethics committees, and establish regional ethics committees to further improve the ability and efficiency of ethics review.

The research on human hepatobiliary development and disorders has been constrained by minimal access to human fetal tissue, and low accuracy of animal models. To overcome this problem, we have established a system for the differentiation of human pluripotent stem cells (hPSCs) into functional hepatobiliary organoids (HBOs). We have previously reported that our 45-d approach closely mimics key stages of hepatobiliary development, starting with the differentiation of hiPSC into endoderm and a small part of mesoderm, and subsequently into hepatoblast-like cells, followed by the parallel generation of hepatocyte-like cells and cholangiocyte-like cells, formation of immature HBO expressing early hepatic and biliary markers, and mature HBO displaying hepatobiliary functionality. In this study, we present an updated version of our previous protocol, which only needs 35 days to achieve maturation in vitro. Furthermore, a hepatobiliary culture medium is developed to functionally maintain the HBOs for more than 1.5 months. The capacity of this approach for producing large amounts of functional HBOs and enabling long-term culture in vitro holds promise for applications on developmental research, disease modeling, as well as screening of therapeutic agents.

Classic hypothalamic-pituitary-end-organ feedback loops – the hypothalamic-pituitary-adrenal axis (HPAA), hypothalamic-pituitary-thyroidal axis (HPTA), and hypothalamic-pituitary-gonadal axis (HPGA) – are associated with the neuroendocrine and immune systems in major depressive disorder (MDD). Female patients with MDD present with evident neuroendocrine and immunological changes. Glucocorticoid, thyroid hormone, and reproductive steroid levels fluctuate with menstrual cycles, which might lead to glucocorticoid receptor resistance, impairment of triiodothyronine conversion, and sex hormone secretion disorders. In this review, we summarize the independent and interactive functions of these three axes in female MDD patients. The similar molecular structure of steroids implies an interrelationship between the hypothalamic-pituitary-end-organ axes and the competitive inhibitory effects at the receptor level, especially when considering the HPAA and HPGA.