Depressive disorder is a prevalent mental illness characterized by pronounced and enduring symptoms of depression and cognitive impairment. The escalating pressures of modern society have led to a corresponding rise in the number of depressive disorder patients, particularly those exposed to adverse social, economic, political, and environmental factors which exacerbate the risk of this disorder. The pathogenesis of depressive disorder is multifaceted, encompassing oxidative stress, neuroplasticity alterations, neuroinflammation, neurotransmitter system imbalances, and intestinal microecological disruptions, among others. Clinically, conventional antidepressants are primarily predicated on the monoamine neurotransmitter hypothesis. This theory posits that depressive disorder can be ameliorated by regulating the levels of neurotransmitters within the body through a singular mechanism. However, the complex and multifaceted pathogenesis of depressive disorder results in limited selectivity for these drugs. Mitogen-activated protein kinase (MAPK) is a conserved serine/threonine kinase that plays a crucial role in various cellular physiological and pathological processes, including cell growth, differentiation, stress adaptation, and inflammatory response. It is instrumental in maintaining cellular homeostasis and regulating cellular responses. Numerous studies indicate that MAPK is involved in the pathogenesis and progression of depressive disorder through various pathogenesis. However, what deserves attention is that the interaction between the pathogenesis and dynamics of regulatory process remains unclear. Modulating MAPK has been shown to influence the onset and progression of depressive disorder, though the precise mechanism remains elusive. Within the MAPK family, aberrant activity of extracellular signal-regulated kinase (ERK) can damage hippocampal neurons and overactivate microglia, precipitating depressive disorder. Excessive activation of c-Jun N-terminal kinase (JNK) results in heightened neuronal apoptosis in the hippocampus and prefrontal cortex, and suppresses the expression of neurotrophic factors. p38, a key regulator in inflammatory reactions, can induce neuroinflammation when overactive, leading to depressive disorder. ERK, JNK, and p38 sub-pathways do not function in isolation but rather interact synergistically and/or antagonistically through shared activators and common target molecules. Consequently, these sub-pathways form a complementary and coordinated regulatory network. In addition, MAPK family members can jointly influence the process of depressive disorder by sharing upstream factors and regulating common downstream targets, and there is a lack of identification of their markers and screening for subgroups. The collective abnormal activities of these MAPK family members illuminate the underlying mechanisms of depressive disorder, suggesting that MAPK could serve as a potential therapeutic target for this disorder. As for the study of ERK, different models of depressive disorder have contradictory effects on its activity. The primary cause of these differences can be attributed to the distinct pathological environments utilized in the creation of depressive disorder models. In the future, it is suggested that we use the inducement of depressive disorder as a modeling standard to accurately simulate the onset of depressive disorder to carry out accurate treatment according to the causes of depressive disorder. Research shows that classic clinical drugs, novel MAPK inhibitors and certain traditional Chinese medicines can prevent and treat depressive disorder by regulating the MAPK signaling pathway. Research on MAPK remains limited, particularly concerning the permeability and cellular specificity across the blood-brain barrier and the identification of objective predictive markers. Although inhibitors face challenges, they also possess significant advantages and developmental potential. This paper systematically summarizes the current status of MAPK in the treatment of depressive disorder, in order to provide insights for researching the pathogenesis of depressive disorder and developing new antidepressant drugs.

Depressive disorder is a prevalent mental illness characterized by pronounced and enduring symptoms of depression and cognitive impairment. The escalating pressures of modern society have led to a corresponding rise in the number of depressive disorder patients, particularly those exposed to adverse social, economic, political, and environmental factors which exacerbate the risk of this disorder. The pathogenesis of depressive disorder is multifaceted, encompassing oxidative stress, neuroplasticity alterations, neuroinflammation, neurotransmitter system imbalances, and intestinal microecological disruptions, among others. Clinically, conventional antidepressants are primarily predicated on the monoamine neurotransmitter hypothesis. This theory posits that depressive disorder can be ameliorated by regulating the levels of neurotransmitters within the body through a singular mechanism. However, the complex and multifaceted pathogenesis of depressive disorder results in limited selectivity for these drugs. Mitogen-activated protein kinase (MAPK) is a conserved serine/threonine kinase that plays a crucial role in various cellular physiological and pathological processes, including cell growth, differentiation, stress adaptation, and inflammatory response. It is instrumental in maintaining cellular homeostasis and regulating cellular responses. Numerous studies indicate that MAPK is involved in the pathogenesis and progression of depressive disorder through various pathogenesis. However, what deserves attention is that the interaction between the pathogenesis and dynamics of regulatory process remains unclear. Modulating MAPK has been shown to influence the onset and progression of depressive disorder, though the precise mechanism remains elusive. Within the MAPK family, aberrant activity of extracellular signal-regulated kinase (ERK) can damage hippocampal neurons and overactivate microglia, precipitating depressive disorder. Excessive activation of c-Jun N-terminal kinase (JNK) results in heightened neuronal apoptosis in the hippocampus and prefrontal cortex, and suppresses the expression of neurotrophic factors. p38, a key regulator in inflammatory reactions, can induce neuroinflammation when overactive, leading to depressive disorder. ERK, JNK, and p38 sub-pathways do not function in isolation but rather interact synergistically and/or antagonistically through shared activators and common target molecules. Consequently, these sub-pathways form a complementary and coordinated regulatory network. In addition, MAPK family members can jointly influence the process of depressive disorder by sharing upstream factors and regulating common downstream targets, and there is a lack of identification of their markers and screening for subgroups. The collective abnormal activities of these MAPK family members illuminate the underlying mechanisms of depressive disorder, suggesting that MAPK could serve as a potential therapeutic target for this disorder. As for the study of ERK, different models of depressive disorder have contradictory effects on its activity. The primary cause of these differences can be attributed to the distinct pathological environments utilized in the creation of depressive disorder models. In the future, it is suggested that we use the inducement of depressive disorder as a modeling standard to accurately simulate the onset of depressive disorder to carry out accurate treatment according to the causes of depressive disorder. Research shows that classic clinical drugs, novel MAPK inhibitors and certain traditional Chinese medicines can prevent and treat depressive disorder by regulating the MAPK signaling pathway. Research on MAPK remains limited, particularly concerning the permeability and cellular specificity across the blood-brain barrier and the identification of objective predictive markers. Although inhibitors face challenges, they also possess significant advantages and developmental potential. This paper systematically summarizes the current status of MAPK in the treatment of depressive disorder, in order to provide insights for researching the pathogenesis of depressive disorder and developing new antidepressant drugs.

ObjectiveTo evaluate the anti-inflammatory activity of the novel magnolol ester derivative YW and to investigate its effects on chondrocyte senescence and preliminary mechanisms. MethodsMagnolol and p-methylbenzoic acid were used as raw materials to synthesize the magnolol ester derivative YW （Molecular Formula： C₂₆H₂₄O₃， Molecular Weight： 384.17， HPLC Purity >96%） via DCC/DMAP-catalyzed esterification. Cytotoxicity was assessed using the CCK-8 assay. A lipopolysaccharide （LPS）-induced RAW264.7 macrophage activation model and an interleukin-1β （IL-1β）-induced rat primary chondrocyte model were established. The release and mRNA expression of inflammatory factors including nitric oxide （NO）， IL-1β， tumor necrosis factor-alpha （TNF-α）， and IL-6 were detected by enzyme-linked immunosorbent assay （ELISA）， Griess reagent method， and quantitative real-time PCR （RT-qPCR）. The expression of senescence markers such as inducible nitric oxide synthase （iNOS）， pro-interleukin-1β （pro-IL-1β）， lysine acetyltransferase 7 （KAT7）， cyclin-dependent kinase inhibitor 1A （p21）， and cyclin-dependent kinase inhibitor 2A （p16）， as well as proteins related to chondrocyte extracellular matrix synthesis and catabolism， were analyzed by Western blot （WB）. Molecular docking was performed using Discovery Studio 2019 to validate target binding. ResultsYW exhibited no significant cytotoxicity at concentrations ≤20 μmol/L. YW concentration-dependently inhibited LPS-induced macrophage inflammatory cytokine release， significantly downregulated iNOS， Pro-IL-1β protein， and inflammatory cytokine mRNA expression （P<0.01）. YW stably bound to KAT7 protein （binding energy： -94.2 kcal/mol）； YW downregulated KAT7 and aging marker protein expression in naturally aged and IL-1β-induced chondrocyte models （P<0.01）； YW regulated chondrocyte matrix synthesis and catabolic protein expression in IL-1β-induced chondrocytes （P<0.01）. ConclusionYW inhibits macrophage activation and inflammatory cytokine release while downregulating KAT7 and senescence marker protein expression in chondrocytes， thereby blocking chondrocyte senescence.

This paper reported a case of severe lupus nephritis in an adolescent with progressive hemolytic anemia, thrombocytopenia, and multiple organs involvement, in which renal damage was characterized by sustained elevation of serum creatinine and oliguria. Accurate diagnosis of lupus nephritis complicated with thrombotic microangiopathy was achieved through genetic testing and molecular technology. The use of double filtration plasmapheresis, blocking B-cell targets and complement activation targets, and supplementing frozen plasma provided more accurate, safe and effective treatment options for patients, which significantly improved prognosis.

This study was aimed at providing basic data for the control and prevention of Yersinia enterocolitica(Ye)infections.Ye isolates from stool samples collected from patients with diarrhea in a Beijing district between January 2019 and June 2024 were studied.Basic patient information and stool samples were collected,and quantitative polymerase chain reaction(qPCR)was applied to enriched cultures.Further analyses included virulence gene detection,whole-genome sequencing,and drug resistance detection.The detection rate of Ye was 0.76%(11/1 439),according to culture methods,thus yielding 12 Ye strains from distinct patients:11 isolated during the study period and 1 from 2017.The 12 Ye positive patients were 6-41 years of age,and their clinical presentations predominantly featured watery stools(66.67%,8/12)and loose stools(33.33%,4/12).The frequencies of nausea,vomiting,and fever were 41.67%(5/12),41.67%(5/12),and 8.33%(1/12),respectively.The drug resistance rates of Ye to TET,AMP,and NAL were 50.00%(6/12),33.33%(4/12),and 25.00%(3/12),respectively.One Ye strain exhibited multidrug resistance to ETP,MEM,TET,CIP,NAL,and AMP.According to qPCR detection of five common virulence genes,two Ye strains were identified as ystA+/ystB-type(ystA+/ystB-/ail+/yadA+/virF+),whereas ten strains were identified as ystA-/ystB+type(ystA-/ystB+/ail-/yadA-/virF-).VFDB database analysis based on genome sequences indicated that 12 Ye strains carried an average of 11 key virulence genes associated with adhesion,invasion,protease activity,and flagellar movement,and predicted 106 virulence genes and 12 virulence gene profiles.Only the two ystA+/ystB-Ye strains contained elements related to the TTSS and ABC transporter function.Detection of ystA-/ystB+Ye in stool isolation and culture of diarrhea cases might potentially have been missed in some cases,thus highlighting the importance of fluorescence PCR screening of fecal growth solutions to enhance isolation efficiency.Moreover,our findings revealed the genetic diversity of Ye isolated from diarrhea cases,thereby indicating the presence of multiple types of virulence genes within this pathogen.

Hepatic encephalopathy is a neuropsychiatric syndrome secondary to severe liver disease.Recent studies have shown that the development of hepatic encephalopathy is closely associated with bile acid/short-chain fatty acid metabolic disorder.As the core theory of traditional Chinese medicine,the theory of Yin and Yang provides a unique perspective for analyzing the association between bile acids/short-chain fatty acids and hepatic encephalopathy.Bile acids function like Yang,governing the free flow of Qi and assisting in metabolic processes,while short-chain fatty acids belong to Yin,maintaining internal stability and conservation,preserving the intestinal barrier,and combating inflammation and toxins.Bile acids and short-chain fatty acids constrain each other and are interdependent to regulate the dynamic equilibrium of the gut-liver-brain axis.On this basis,by regulating the metabolic imbalance of bile acids and short-chain fatty acids,it is expected to restore the dynamic balance of Yin and Yang in patients with hepatic encephalopathy under the synergistic intervention of traditional Chinese medicine and Western medicine.

Objective To evaluate the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets using hydroxyethyl starch(HES)130/0.4 sodium chloride injection as an extraction medium.Methods Firstly,40 Sprague Dawley(SD)rats including 20 male and 20 female ones were seleted and randomly enrolled into a sample group and a control group by sex,with 20 ones in each group.Secondly,instead of plasma HES 130/0.4 sodium chloride injection was used to leach disposable plasma virus-inactivated blood transfusion sets to prepare the test solution by simulating clinical application such as lighting,adsorption and filtration and storage.Finally,the test solution and HES 130/0.4 sodium chloride injection were injected into the tail vein of the SD rats at a dose of 20 mL/kg for 28 d in the sample group and in the control group respectively,and the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets and the feasibility of using HES 130/0.4 sodium chloride injection as the extraction medium to assess their subchronic systemic toxicity were evaluated with clinical observation,body mass monitoring,clinical pathology examination,gross necropsy and histopathology examination.Results The sample group and control group had no significant differences in mortality rates,clinical observation results,body mass,gross necropsy results,hematological and coagulation examination results and organ weight(all P>0.05);blood biochemical examinations showed the male rats in the sample group had the cholesterol(CHO)values higher while the creatinine(CR)values lower than those in the control group,with the differences being statistically significant(both P<0.05)and the two indexes within the range of the laboratory's historical reference data,and other blood biochemical indexes were not significantly different(all P>0.05);the sample group had the spleen weight-to-body mass ratios of the female rates lower significantly than those in the control group(P<0.05),and the ratios of other organ weight to body mass had significant differences(all P>0.05);histopathology examination showed slight pathological changes in liver,spleen and kidney of female rats and in spleen and kidney of male rats in the sample group,and the female and male rats in the control group had similar pathological changes found in the sample group,which might be caused by HES metabolites.Conclusion Disposable plasma virus-inactivated blood transfusion sets prove to have no significant subchronic systemic toxicity,and its feasible to use HES 130/0.4 sodium chloride injection as the extraction medium to evaluate the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets.[Chinese Medical Equipment Journal,2025,46(10):29-35]

OBJECTIVE: To analyze the factors influencing the development of refeeding syndrome (RFS) in patients with sepsis and its impact on clinical prognosis. METHODS: A retrospective case-control study method was used to collect the clinical data of patients with sepsis admitted to the intensive care unit (ICU) of Qingdao Municipal Hospital from December 2018 to December 2023. The patients were divided into RFS and non-RFS groups according to whether RFS occurred, and the basic data, nutritional status and assessment scale, laboratory indicators, nutritional intake, medical history and prognosis were compared between the two groups. Binary multifactorial Logistic regression analysis was used to screen the influencing factors of the occurrence of RFS in patients with sepsis. RESULTS: A total of 544 patients with sepsis were finally enrolled, of whom 250 did not develop RFS and 294 developed RFS, with an incidence of 54.0%. Compared with the non-RFS group, the patients in the RFS group had lower body mass index (BMI), albumin, prealbumin, baseline electrolytes (serum phosphorus, serum potassium, and serum magnesium), creatinine-height index, and protein intake, and had higher nutritional risk screening 2002 (NRS2002) score, sequential organ failure assessment (SOFA) score, calorie intake, and the proportions of feedings during the 48 hours of ICU admission, history of diabetes and septic shock. Binary multifactorial Logistic regression analysis showed that BMI [odds ratio (OR) = 0.910, 95% confidence interval (95%CI) was 0.857-0.947, P < 0.001], SOFA score (OR = 1.166, 95%CI was 1.085-1.254, P < 0.001), albumin (OR = 0.946, 95%CI was 0.902-0.991, P = 0.019), baseline serum phosphorus (OR = 0.343, 95%CI was 0.171-0.689, P = 0.003), baseline serum potassium (OR = 0.531, 95%CI was 0.377-0.746, P < 0.001), creatinine-height index (OR = 0.891, 95%CI was 0.819-0.970, P = 0.008), caloric intake (OR = 1.108, 95%CI was 1.043-1.178, P = 0.001), protein intake (OR = 0.107, 95%CI was 0.044-0.260, P < 0.001), and feedings during the 48 hours of ICU admission (OR = 0.592, 95%CI was 0.359-0.977, P = 0.040) and septic shock (OR = 0.538, 95%CI was 0.300-0.963, P = 0.037) were independent influence factors on the occurrence of RFS in septic patients. Of the 544 patients, 267 died at 28 days, with a mortality of 49.1%. The 28-day mortality of patients in the RFS group was significantly higher than that in the non-RFS group [54.4% (160/294) vs. 42.8% (107/250); χ² = 7.302, P = 0.007]. 544 patients had a length of ICU stay of 20 (17, 24) days. The patients in the RFS group had a significantly longer length of ICU stay than that in the non-RFS group [days: 20 (17, 25) vs. 19 (17, 23); Z = -2.312, P = 0.021]. CONCLUSIONS The incidence of RFS in septic patients is high. Factors influencing the occurrence of RFS in septic patients include BMI, SOFA score, albumin, baseline serum phosphorus, baseline serum potassium, caloric intake, protein intake, feeding within 48 hours of ICU admission, and septic shock. RFS prolongs the length of ICU stay and increases the 28-day mortality in patients with sepsis.
Humans ; Retrospective Studies ; Sepsis/complications* ; Prognosis ; Refeeding Syndrome/etiology* ; Case-Control Studies ; Intensive Care Units ; Male ; Nutritional Status ; Female ; Risk Factors ; Middle Aged ; Logistic Models ; Body Mass Index ; Aged

Multiple myeloma(MM)is a hematologic malignancy characterized by the malignant prolifer-ation of plasma cells.Currently,proteasome inhibitors(PIs),immunomodulatory drugs(IMiDs),and autologous hematopoietic stem cell transplantation(ASCT)are the primary approaches used to improve the survival outcomes of MM patients.However,as treatment advances,most patients still face refractory and relapsed diseases,and the path to a cure remains challenging.In recent years,monoclonal antibod-ies(mAbs),chimeric antigen receptor T cells(CAR-T),antibody-drug conjugates(ADCs),and bispe-cific antibodies(BsAbs)have all demonstrated promising efficacy in clinical studies and applications.These antibody and cell-based immunotherapies have brought new hope to patients with refractory and re-lapsed MM(RRMM).Each type of immunotherapy offers unique advantages in activating immune cells,targeting tumors,and improving patient outcomes,yet they also encounter challenges related to safety and resistance.In the future,with continuous advancements in molecular biology and antibody engineering,novel immunotherapeutic products are expected to achieve synergistic effects through combination strate-gies,thereby providing longer survival benefits and improved life quality for RRMM patients.This article aims to review the latest progress in immunotherapy for MM,systematically discussing the mechanisms of action,current clinical applications,and future development trends of mAbs,CAR-T,ADCs,and BsAbs.It is intended to serve as a comprehensive reference for researchers and clinicians and promote advancing precision immunotherapy for MM.

Objective:To investigate the feasibility of varicocele ligation with mobile phone microscope.Methods:The high-performance mobile phone and mobile phone stand were combined to act as a mobile phone microscope.And the varicocele ligation was performed under the mobile phone microscope.Results:All five patients successfully underwent varicocelectomy under the guidance of a mobile phone microscope.The average operation time was(112.8±52.2)with ranged from 74.0 to 195.0 minutes.Three pa-tients completed the follow-up after the operation with the proportion of improved sperm quality reaching 100.0％(3/3).Conclusion:High-performance mobile phone microscope can be used for varicocele ligation.