Guided by the theory of latent pathogens， it is believed that the basic pathogenesis of adult-onset Still's disease is the latent pathogens in the deep yin level. The onset of the disease is fundamentally characterized by the deficiency of both qi and yin as the root， with dampness， heat， phlegm， and blood stasis as the branch， which triggered by intruding pathogens activate the latent pathogens in yin level. The treatment focuses on nourishing yin and dispersing heat as the key therapeutic method. It is proposed that clearing and resolving dampness-heat， expelling pathogens outward， dispersing the latent pathogens， reinforcing healthy qi and consolidating the root， boosting qi and nourishing yin as treatment idea. In clinic， Qinghao Biejia Decoction （青蒿鳖甲汤） could be used as the basic formula， and modified with characteristic herb pairs such as Qinghao （Artemisia annua） - Digupi （Lycium chinense） to enrich yin and clear heat， and enforce the power of clearing deficient heat； Biejia （Lawsonia inermis） - Xuchangqing （Vincetoxicum mukdenense） to enrich yin and activate blood， unblock the collaterals and dissipate masses； Duhuo （Angelica biserrata） - Mudanpi （Paeonia × suffruticosa） to dispel wind and activate blood， resolve dampness and unblock the collaterals， so as to clear and warm simultaneously， and regulate qi and blood at the same time； and Chuanshanlong （Dioscorea nipponica） - Difuzi （Bassia scoparia） to dissolve stasis and dispel phlegm， explore and dispel latent pathogens.

Mitochondria serve as multifunctional powerhouses within cells, coordinating essential biological activities that are critical for cell viability, including material metabolism, signal transduction, and the maintenance of homeostasis. They support cells in adapting to complex and fluctuating environments. Oocytes, being the largest cells in multicellular organisms, contain a high number of mitochondria with unique structural characteristics. Mitochondria play active roles in the development and maturation of oocytes. A decline in mitochondrial function negatively affects both the quality and quantity of oocytes, thereby contributing to ovarian aging. However, the specific mechanisms through which mitochondrial dysfunction influences the progression of ovarian aging and impacts reproductive longevity remain unclear. Furthermore, medical strategies aimed at rejuvenating mitochondria to restore ovarian reserve and improve female reproductive potential may open new avenues for clinical treatment. In this review, we summarize the current understanding and key evidence regarding the role of mitochondrial dysfunction in ovarian aging and present emerging medical approaches targeting mitochondria to alleviate premature ovarian aging and enhance reproductive performance.
Humans ; Female ; Mitochondria/physiology* ; Ovary/physiology* ; Aging/physiology* ; Animals ; Oocytes/metabolism*

Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants and young children, as well as an important cause of respiratory tract infections in immunocompromised patients and the elderly, which poses a significant economic and social burden worldwide. In recent years, substantial progress has been made in understanding the structure and function of RSV proteins and the interactions between RSV with host factors which is helpful to the discovery of new therapeutic targets and the development of novel interventions. Although two vaccines and two monoclonal antibodies for RSV prevention have been approved, the antiviral treatment remains an unmet clinical need. In this review, we summarize the structure, protein functional properties, and pathological mechanisms of RSV and the current status of RSV drug development. In addition, remaining challenges and innovative ideas for RSV prevention and treatment have also been highlighted.

Immunotherapy has become a pivotal modality in clinical cancer treatment. However, its effectiveness is limited to a small subset of patients due to the low antigenicity, impaired innate response, and various adaptive immune resistance mechanisms of the tumor microenvironment (TME). Accumulating evidence reveals the critical roles of metal elements in shaping immunity against tumor progression and metastasis. The marriage of metalloimmunotherapy and nanotechnology further presents new opportunities to optimize the physicochemical and pharmacokinetic properties of metal ions in a precise spatiotemporal control manner. Several metallodrugs have demonstrated encouraging immunotherapeutic potential in preliminary studies and are currently undergoing clinical trials at different stages, yet challenges persist in scaling up production and addressing long-term biosafety concerns. This review delineates how metal materials modulate biological activities across diverse cell types to orchestrate antitumor immunity. Moreover, it summarizes recent progress in smart drug delivery-release systems integrating metal elements, either as cargo or vehicles, to enhance antitumor immune responses. Finally, the review introduces current clinical applications of nanomedicines in metalloimmunotherapy and discusses potential challenges that impede its widespread translation into clinical practice.

Objective:To investigate the effect of β-elemene on mitochondrial structure and function of the A549 cells of non-small cell lung cancer(NSCLC),and to elucidate the mechanism of β-elemene in the treatment of NSCLC.Methods:The A549 cells at logarithmic growth stage were divided into blank control group(0 mng·L-1 β-elemene),low,medium and high doses of β-elemene groups(10,25 and 50 mg·L-1),and solvent control group(0.5％ethanol in equal volume).After treatment for 24 h,the cell activities in various groups were detected by MTT assay;the morphology changes of mitochondria in the cells in various groups was observed by transmission electron microscope;the levels of adenosine 5′-triphosphate(ATP)in the cells in various groups were detected by colorimetry;the mitochondrial membrane potential of the A549 cells in various groups were detected by JC-1 flow cytometry;mitochondrial membrane permeability transfer hole assay was used to detect the mitochondrial membrane permeabilities of the cells in various groups.Results:The MTT results showed that compared with blank control group,the cell activities in low,medium and high doses of β-elemene groups were decreased gradually(P＜0.05),while the cell activity in solvent control group had no significant change,and the difference was not significant(P＞0.05).The transmission electron microscope results showed that compared with blank control group,the mitochondria of A549 cells in low,medium and high doses ofβ-elemene groups showed swelling,vacuolation,disordered arrangement and dissolution,while the mitochondrial morphology of the A549 cells in solvent control group had no significant changes.The colorimetric method results showed that compared with blank control group,the ATP levels in the A549 cells in low,medium and high dose β-elemene groups were gradually decreased(P＜0.05),while the ATP level in the A549 cells in solvent control group had no significant change,and the difference was not significant(P＞0.05).The JC-1 flow cytometry method results showed that compared with blank control group,the mitochondrial membrane potential of the A549 cells in low,medium and high doses ofβ-elemene groups were decreased,and the percentages of the cells in Q2-4 region were increased(P＜0.05);the percentage of the A549 cells in the Q2-4 region in solvent control group had no significant change.The results of mitochondrial membrane permeability transfer hole experiment showed that compared with blank control group,the mitochondrial membrane permeabilities of the A549 cells in low,medium and high doses of β-elemene groups were increased,and the percentages of the cells in M4 region were increased(P＜0.05);the mitochondrial membrane permeability of the A549 cells and the percentage of the M4 cells in solvent control group had no significant changes,and the difference was not significant(P＞0.05).Conclusion:β-elemene can inhibit the proliferation of the A549 cells,and the mechanism may be that the mitochondrial structure of A549 cells is damaged by reducing the level of ATP and mitochondrial membrane potential,changing the mitochondrial morphology and increasing the mitochondrial membrane permeability.

Objective To evaluate the influencing factors of aspiration in neurological critically ill patients by Meta-analysis.Methods PubMed,Embase,Web of Science,CNKI,and Wanfang Data were searched from inception to 1 October,2023,to obtain relevant studies on influencing fac-tors of aspiration in neurological critically ill patients.The literature screening,data extraction and quality evaluation were completed by two researchers.RevMan 5.4 and Stata 13.0 software were ap-plied for pooled Meta-analysisand assessed publication bias,respectively.Results A total of 8 arti-cles,including 1,315 neurocritical care patients,were included in this study.Nine influencing factors related to aspiration were extracted for Meta-analysis.The Meta-analysis results showed that the three influencing factors that caused aspiration in neurocritical care patients were stroke history(OR=5.03,95％CI,2.71 to 9.32,P＜0.000 01),National Institutes of Health Stroke Scale(NIHSS)score＞10(OR=3.35,95％CI,1.75 to 6.42,P=0.000 3),and gastric residual volume＞150mL(OR=7.13,95％CI,2.55 to 9.96,P=0.001).Conclusion This study provides a scientific basis for clinical healthcare professionals to early identify high-risk patients for aspiration,take targeted inter-vention measures,and prevent the occurrence of aspiration.

Objective To explore the influencing factors of cognitive impairment in non-dialysis patients with chronic kidney disease(CKD).Methods A total of 60 hospitalized non-dialysis patients with CKD in the Department of Nephrology of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from September 2022 to September 2023 were enrolled as research objects.According to the estimated glomerular filtration rate(eGFR),they were divided into stage 1 to 2 of CKD group[eGFR ≥60 mL/(min·1.73 m2)]with 23 cases,the stage 3 of CKD group[eGFR 30～＜60 mL/(min·1.73 m2)]with 20 cases,and stage 4 to 5 of CKD group[eGFR＜30 mL/(min·1.73 m2)]with 17 cases.The Montreal Cognitive Assessment Scale(MoCA)was used to evaluate the cognitive function of the patients.Basic data and common clinical laboratory in-dicators on hospital admission were collected to analyze the differences in cognitive function levels under different renal function statuses and to explore the influencing factors of cognitive impairment.Results The incidence rates of cognitive impairment in the stage 1 to 2 of CKD group,stage 3 of CKD group,and stage 4 to 5 of CKD group were 47.8％,85.0％,and 94.1％respectively,the median MoCA scored 26,24 and 20 respectively,with statistically significant between-group differ-ences(P＜0.05).Cognitive function was significantly negatively correlated with age(r=-0.634,P＜0.001),blood urea nitrogen(BUN)(r=-0.574,P＜0.001),serum creatinine(Cr)(r=-0.417,P＜0.001),cystatin C(Cys-C)(r=-0.327,P=0.011),serum β2-microglobulin(β2-MG)(r=-0.259,P=0.046),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(r=-0.474,P＜0.001),and was significantly positively correlated with hemoglobin(HB)(r=0.401,P=0.001)and eGFR(r=0.485,P＜0.001).Multivariate Logistic regression analysis showed that age(P=0.006)and NT-proBNP(P=0.041)were influencing factors of cognitive im-pairment in non-dialysis patients with CKD.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of age for prediction were 0.860,0.864 and 0.812 respectively,the AUC,sensitivity,and specificity of NT-proBNP for pre-diction were 0.808,0.795 and 0.875 respectively,and the combined prediction of age and NT-proBNP had an AUC,sensitivity,and specificity of 0.893,0.955,and 0.750,respectively.Conclusion As renal function deteriorates,the incidence rate and severity of cognitive impairment in non-dialysis patients with CKD tend to increase.Advanced age,renal function deterioration,high NT-proBNP level,and anemia are associated with the occurrence of cognitive impairment in non-di-alysis patients with CKD,among which age and NT-proBNP are influencing factors for cognitive im-pairment.

In the era of rational molecular design of fusion proteins,linker selection has garnered significant attention as a critical determinant of construct functionality.Suboptimal selection of linkers may result in such structural perturbations as protein misfolding,reduced expression yields,and compromised bioactivity.Consequently,the strategic selection of linkers tailored to specific objectives of molecular design by optimizing spatial orientation,maintaining domain autonomy or enabling post-translational modifications has emerged as a pivotal research frontier.Given these challenges,this review outlines the common properties of linkers,ways of classification,and the functional-structural interplay in current applications.Furthermore,we propose context-dependent selection frameworks for therapeutic proteins,biosensors,and enzyme cascades,which can serve as a systematic methodology to guide linker optimization in next-generation fusion protein engineering.

BACKGROUND:Reducing the rate of abnormal fertilization is an effective approach to improving the efficacy of in vitro fertilization and reducing patients'financial strain.However,the current research on abnormal fertilization has focused on exploring the types of prokaryotic nuclei and their generation mechanisms,as well as analyzing embryos formed by abnormal fertilization,chromosomal ploidy and utilization value.There is a lack of clinical prediction models for abnormal fertilization based on retrospective studies. OBJECTIVE:To construct a nomogram model to predict abnormal female factors in in vitro fertilization. METHODS:A total of 5 075 patients undergoing treatment for conventional in vitro fertilization at Nanxishan Hospital of Guangxi Zhuang Autonomous Region from March 2017 to March 2022 were retrospectively analyzed.The male confounders were calibrated on a 1:1 propensity score with a match tolerance of 0.02,and 1 672 cases were successfully matched.According to the Vienna Consensus,patients with≥60%normal fertilization capacity were included in the normal fertilization group(n=836)and those with<60%normal fertilization capacity were included in the abnormal fertilization group(n=836).The model and validation groups were obtained by random sampling at a ratio of 7:3.Factors related to the occurrence of abnormal fertilization following conventional in vitro fertilization in the model group were screened using univariate analysis and the best matching factors were selected using the Least Absolute Shrinkage and Selection Operator(LASSO)and included in a multifactorial forward stepwise Logistic regression to identify their independent influencing factors and plot a nomogram.Finally,the prediction model was validated for discrimination,accuracy and clinical application efficacy using receiver operating characteristic curves,calibration curves,clinical decision curves and clinical impact curves. RESULTS AND CONCLUSION:The univariate analysis indicated the factors influencing the occurrence of abnormal fertilization were age,controlled ovarian hyperstimulation protocol,number of assisted pregnancies,years of infertility,infertility factors,anti-mullerian hormone,sinus follicle count,basal luteinizing hormone,luteinizing hormone concentration on the human chorionic gonadotropin day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).LASSO regression further identified the best matching factors,including age,microstimulation protocol,number of assisted pregnancies,years of infertility,anti-mullerian hormone,luteinizing hormone level on human chorionic gonadotropin injection day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).Multifactorial forward stepwise Logistic regression results showed that age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day were independent influencing factors for the occurrence of abnormal fertilization following conventional in vitro fertilization.The receiver operating characteristic curves showed an area under the curve of 0.761(0.746,0.777)for the model group and 0.767(0.733,0.801)for the validation group,indicating that the model has good discrimination.The mean absolute error of the calibration curve was 0.044,and the Hosmer-Lemeshow test indicated that there was no significant difference between the predicted probability of abnormal fertilization and the actual probability of abnormal fertilization(P>0.05),indicating the prediction model has good consistency and accuracy.The clinical decision curves and clinical impact curves showed that the model and validation groups had the maximum net clinical benefit at valve probability values of 0.00-0.52 and 0.00-0.48,respectively,and there was a good clinical application efficacy in this valve probability range.To conclude,the nomogram model has good discrimination and accuracy as well as clinical application efficacy for predicting the occurrence of abnormal fertilization in women undergoing conventional in vitro fertilization based on age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day.

BACKGROUND:Due to the mismatch between the design of the proximal femoral nail antirotation Asian version(PFNA-Ⅱ)and Asian population,extrusion of the proximal femoral intertrochanteric nail may occur in the treatment of femoral intertrochanteric fractures.The influence of the protruding length on the curative effect of the operation needs to be further discussed. OBJECTIVE:To quantitatively measure the protruding length of the proximal trochanter of the femur with intramedullary nail after PFNA-Ⅱ,and to analyze the effect of protruding length on the efficacy of PFNA-Ⅱ in the treatment of femoral intertrochanteric fractures. METHODS:Totally 68 patients with femoral intertrochanteric fractures treated with PFNA-Ⅱ internal fixation in the First Affiliated Hospital of Anhui Medical University were selected.The extramedullary process of the proximal trochanter of the femur was quantitatively measured on the anterior and posterior X-ray films of the hip joint within 6 months after operation.According to the existence of extrusion of the proximal trochanter intramedullary nail,the patients were divided into protruding group and non-protruding group.The data of sex,height,fracture type,length and diameter of the intramedullary nail,the position of screw blade in the femoral neck and protruding length of proximal greater trochanter were collected.The postoperative curative effect was judged by visual analog scale pain score and hip joint Harris score at 6 months after operation.The influence of protruding proximal trochanter of the PFNA-Ⅱ intramedullary nail on the operative effect was observed. RESULTS AND CONCLUSION:(1)There were significant differences in sexual characteristics between the protruding group and the non-protruding group(P=0.001).(2)According to AO/OTA classification,there were no significant differences in fracture type between the protruding group and the non-protruding group(P=0.289).(3)There was no significant difference in the length and diameter of the intramedullary nail between the two groups(P=0.067,P=1.000).(4)There was no significant correlation between the height of all patients and the length of the intramedullary nail(P=0.510),but there was a significant correlation between height and protruding length(P=0.034).There was no significant correlation between screw blade position and protruding length(P=0.968).(5)Six months after operation,there was no significant difference in the hip Harris score(P=0.373),but the visual analog scale pain score was significantly higher in the protruding group than that in the non-protruding group(P=0.000).(6)The results suggest that nail extrusion often occurs in the proximal greater trochanter when PFNA-Ⅱ is used in the treatment of intertrochanteric fractures in Asians.When the nail extended into the proximal soft tissue of the greater trochanter,patients complained of proximal greater trochanteric pain and the visual analog scale score of proximal greater trochanter pain in the patient was significantly higher than that in the non-protruding group.To be more suitable for the Asian population,we suggest that the PFNA-Ⅱ should be improved to further shorten the proximal nail end to obtain better clinical results of femoral intertrochanteric fracture fixation.