Selenoproteins, as the active form of selenium, play an important role in various physiological and pathological processes, such as anti-oxidation, anti-tumor, immune response, metabolic regulation, reproduction and aging. Although the expression level of selenoproteins in adipose tissue is significantly influenced by dietary selenium intake, it is closely related to the homeostasis of adipose tissue. In this review, we summarized the role of selenoproteins in the physiological function of adipose tissue and the pathogenesis of obesity in recent years, in order to provide a rationale for developing potential therapeutic agents for the treatment of obesity and related metabolic diseases.
Selenoproteins/metabolism* ; Adipose Tissue/physiology* ; Obesity/metabolism* ; Humans ; Animals ; Selenium

Based on the α7 nicotinic acetylcholine receptor(α7nAChR), this study examined how tetrahydropalmatine(THP) affected BV2 microglia exposed to lipopolysaccharide(LPS), aiming to clarify the possible mechanism underlying the anti-depression effect of THP from the perspectives of preventing inflammation and regulating polarization. First, after molecular docking and determination of the content of Corydalis saxicola Bunting total alkaloids, THP was initially identified as a possible anti-depression component. The BV2 microglia model of inflammation was established with LPS. BV2 microglia were allocated into a normal group, a model group, low-and high-dose(20 and 40 μmol·L~(-1), respectively) THP groups, and a THP(20 μmol·L~(-1))+α7nAChR-specific antagonist MLA(1 μmol·L~(-1)) group. The CCK-8 assay was used to screen the safe concentration of THP. A light microscope was used to examine the morphology of the cells. Western blot and immunofluorescence were used to determine the expression of α7nAChR. qRT-PCR was performed to determine the mRNA levels of inducible nitric oxide synthase(iNOS), cluster of differentiation 86(CD86), suppressor of cytokine signaling 3(SOCS3), arginase-1(Arg-1), cluster of differentiation 206(CD206), tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. The experimental results showed that THP at concentrations of 40 μmol·L~(-1) and below had no effect on BV2 microglia. THP improved the morphology of BV2 microglia, significantly up-regulated the protein level of α7nAChR, significantly down-regulated the mRNA levels of iNOS, CD86, SOCS3, TNF-α, IL-6, and IL-1β, significantly up-regulated the mRNA levels of Arg-1 and CD206, and dramatically lowered the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. However, the antagonist MLA abolished the above-mentioned ameliorative effects of THP on LPS-treated BV2 microglia. As demonstrated by the aforementioned findings, THP protected LPS-treated BV2 microglia by regulating the M1/M2 polarization and preventing inflammation, which might be connected to the regulation of α7nAChR on BV2 microglia.
Berberine Alkaloids/chemistry* ; alpha7 Nicotinic Acetylcholine Receptor/chemistry* ; Microglia/metabolism* ; Mice ; Animals ; Cell Line ; Corydalis/chemistry* ; Humans ; Molecular Docking Simulation ; Inflammation/drug therapy* ; Nitric Oxide Synthase Type II/immunology* ; Tumor Necrosis Factor-alpha/immunology*

OBJECTIVE: To assess relationships between cold spells and genitourinary hospitalization risk. METHODS: Hospitalization records for genitourinary system diseases (GUDs) from 16 districts in Beijing (2013-2018) were analyzed. Cold spells were defined based on varying intensity thresholds. A two-stage analytical method was employed: first, generalized linear models assessed district-specific associations between cold spells and hospitalizations; second, random-effects meta-analysis aggregated the district-level results. Subgroup analyses were performed by admission type (emergency vs. outpatient), age, and sex. RESULTS: A total of 271,579 GUD-related hospitalizations were recorded. Cold spells (p1day2，daily mean temperature below the 1 ^st percentiles of the daily mean temperature distribution from January 1, 2013, to December 31, 2018, lasting for two or more consecutive days) were linked to a significant rise in hospitalization risks: 1.43 (95% CI: 1.32-1.56) for all GUDs, 1.35 (95% CI: 1.23-1.49) for urinary system diseases, and 1.46 (95% CI: 1.28-1.67) for renal failure, when compared to non-cold spell days. Emergency admissions showed higher risk increases than outpatient admissions. CONCLUSION Extreme cold spells significantly elevate hospitalization risks for GUDs. This highlights the urgent need for targeted public health interventions to mitigate cold-related health impacts, especially for vulnerable populations.
Humans ; Hospitalization/statistics & numerical data* ; Male ; Female ; Cold Temperature/adverse effects* ; Infant ; Child, Preschool ; Middle Aged ; Adult ; Child ; Aged ; Adolescent ; Young Adult ; Beijing/epidemiology* ; Female Urogenital Diseases/etiology* ; Male Urogenital Diseases/etiology* ; Infant, Newborn ; Risk Factors

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

Refractory depression is a drug-resistant subtype of major depressive disorder for which there is a lack of effective and durable treatments.Seroxibine,the active substance in the mushroom Capsicum annuum,is a natural 5-hydroxytryptamine hallucinogen that activates the 5-hydroxytryptamine 2A receptor to mediate multiple aspects of antidepressant effects.In recent years,it has received renewed attention for its outstanding therapeutic effects in the treatment of refractory depression or other psychiatric disorders.Therefore,this paper summarizes the studies on neuroplasticity,brain neural connectivity network,neurotransmitters,immune factors,microbiota-gut-brain axis,and clinical efficacy of seloxipine in domestic and international literature,and explores the possible mechanisms of seloxipine's effect on refractory depression,with a view to providing theoretical basis for the clinical application of this drug.

Purpose::Although traditional craniotomy (TC) surgery has failed to show benefits for the functional outcome of intracerebral hemorrhage (ICH). However, a minimally invasive hematoma removal plan to avoid white matter fiber damage may be a safer and more feasible surgical approach, which may improve the prognosis of ICH. We conducted a historical cohort study on the use of multimodal image fusion-assisted neuroendoscopic surgery (MINS) for the treatment of ICH, and compared its safety and effectiveness with traditional methods.Methods::This is a historical cohort study involving 241 patients with cerebral hemorrhage. Divided into MINS group and TC group based on surgical methods. Multimodal images (CT skull, CT angiography, and white matter fiber of MRI diffusion-tensor imaging) were fused into 3 dimensional images for preoperative planning and intraoperative guidance of endoscopic hematoma removal in the MINS group. Clinical features, operative efficiency, perioperative complications, and prognoses between 2 groups were compared. Normally distributed data were analyzed using t-test of 2 independent samples, Nonnormally distributed data were compared using the Kruskal-Wallis test. Meanwhile categorical data were analyzed via the Chi-square test or Fisher’s exact test. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. Results::A total of 42 patients with ICH were enrolled, who underwent TC surgery or MINS. Patients who underwent MINS had shorter operative time ( p < 0.001), less blood loss ( p < 0.001), better hematoma evacuation ( p =0.003), and a shorter stay in the intensive care unit ( p =0.002) than patients who underwent TC. Based on clinical characteristics and analysis of perioperative complications, there is no significant difference between the 2 surgical methods. Modified Rankin scale scores at 180 days were better in the MINS than in the TC group ( p =0.014). Conclusions::Compared with TC for the treatment of ICH, MINS is safer and more efficient in cleaning ICH, which improved the prognosis of the patients. In the future, a larger sample size clinical trial will be needed to evaluate its efficacy.

Objective To evaluate the efficacy of double U-stitch and modified"double U-stitch pancreaticojejunostomy"in pancreaticoduodenectomy.Methods We retrospectively analyzed the clinical information of 150 patients who underwent pancreaticoduodenectomy between January 2022 and September 2023 in Wang Wei's team in department of pancreatic surgery,Fudan University Shanghai Cancer Center.The patients were divided into two groups according to the pancreaticojejunostomy method:the double U-stitch 1.0 group(70 cases before modification)and the double U-stitch 2.0 group(80 cases after modification).The postoperative complications of the two groups were compared.Results The overall postoperative complications were significantly lower in the double U-stitch 2.0 group as compared with the double U-stitch 1.0 group(13.8％vs.38.6％,P=0.001).The incidence of clinically relevant pancreatic fistula was 18.6％in the double U-stitch 1.0 group,while this was significantly decreased in the double U-stitch 2.0 group(6.3％)(P=0.021).Postoperative extraluminal hemorrhage occurred in 5 patients in the double U-stitch 1.0 group,while in the double U-stitch 2.0 group,only one patient experienced postoperative intraluminal hemorrhage,the difference was statistically significant between two groups(P=0.007).The median postoperative length of hospital stay was significantly shorter in the double U-stitch 2.0 group than that in the double U-stitch 1.0 group(11d vs.14 d,P=0.001).Conclusions The modified"double U-stitch pancreaticojejunostomy"can significantly reduce the incidence of clinically relevant pancreatic fistula and other relevant severe complications,which helps improve the safety of the procedure.

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.