Objective: To explore the correlation between the expression levels of endoplasmic reticulum stress(ERS) and trophoblast apoptosis-related markers and severe preeclampsia(SPE) in placental tissues of pregnant women with early-and late-onset SPE and normal pregnancy. Methods: Placental tissues from 20 early and late haired severe preeclamptic singleton pregnant women who attended the Hospital were collected(early-onset group, late-onset group), and 20 cases pregnant women of normal blood pressure and no other pregnancy complications who delivered in our hospital during the same period were selected as the normal group. Transmission electron microscopy was used to observe the ultrastructure of the endoplasmic reticulum of trophoblast cells in placental tissues. Protein blotting assay was used to detect the expression levels of endoplasmic reticulum stress-related proteins, including Glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), Phosphorylated eukaryotic translation initiation factor 2α(p-eIF2α) and Phosphatidylinositol-requiring enzyme 1(p-IRE1)α. Immunohistochemistry assay was used to detect the expression of proliferating cell nuclear antigen(Ki67), a proliferation marker, in placental tissues, and TUNEL staining was used to detect placental tissue trophoblast apoptosis. Results: The endoplasmic reticulum of trophoblast cells in the placental tissues of the normal pregnant women group was normal in volume, with no dilatation or swelling. In contrast, the endoplasmic reticulum of placental tissues in the severe preeclampsia group showed obvious edema and significant dilatation, and the dilatation was more obvious in the early-onset group than in the late-onset group. The expression level of endoplasmic reticulum stress-related proteins GRP78(P<0.001,P<0.05) and CHOP(P<0.01,P<0.001), the phosphorylation levels of eIF2α(P<0.000 1,P<0.01) and IRE1α(P<0.000 1,P<0.001) increased in placental tissues of both early-onset and late-onset groups compared to those of the normal group. The p-eIF2α/eIF2α(P<0.001) to p-IRE1α/IRE1α ratio(P<0.05) and GRP78(P<0.01) protein expression levels were significantly higher in the early-onset group than in the late-onset group. Compared with the normal group, the number of Ki67-positive cells per field of view was significantly reduced in the early-onset and late-onset groups(P<0.000 1,P<0.05), and the number of Ki67-positive cells was significantly lower in the early-onset group than in the late-onset group(P<0.01). There were more positive apoptotic cells per field of view in the placental tissues of the early-onset group, and the apoptosis rate of trophoblast cells was significantly higher than that in the other two groups(P<0.001,P<0.01). Conclusion Increased trophoblast apoptosis and suppressed proliferation in placental tissues of patients with severe preeclampsia may be associated with endoplasmic reticulum stress overactivation, and the activation level is higher in placental tissues of early-onset severe preeclampsia than that of late-onset group.

Charcoal-processed traditional Chinese herbal medicine has various therapeutic effects， including astringing， hemostasis， anti-diarrhea， clearing heat， tonifying， and warming the interior. This paper summarizes the clinical application features， compatible experiences， dosages， and precautions for over 20 types of charcoal-processed herbal medicine in the treatment of gynecological bleeding disorders caused by dysfunctions such as dysfunctional uterine bleeding， endometriosis， uterine incision pseudocavity， and vaginal bleeding resulting from threatened miscarriage. The charcoal-processed herbal medicine include Huangqin （Scutellaria Baicalensis） Charcoal， Dahuang （Rheum Palmatum） Charcoal， Cebai （Platycladus Orientalis） Charcoal， Diyu （Sanguisorba Officinalis） Charcoal， Daji （Cirsium Setosum） Charcoal， Xiaoji （Cirsium Japonicum） Charcoal， Shengdi （Rehmannia Glutinosa） Charcoal， Aiye （Artemisia Argyi） Charcoal， Paojiang （Zingiber Officinale） Charcoal， Xuduan （Dipsacus Asper） Charcoal， Duzhong （Eucommia Ulmoides） Charcoal， Qiancao （Rubia Cordifolia） Charcoal， Puhuang （Typha Angustifolia） Charcoal， Shanzha （Crataegus Pinnatifida） Charcoal， Jingjie （Schizonepeta Tenuifolia） Charcoal， Xueyu （Carthamus Tinctorius） Charcoal， Zonglyu （Areca Catechu） Charcoal， Wumei （Prunus Mume） Charcoal， Shudahuang （Rheum Officinale） Charcoal， Lianfang （Nymphaea Alba） Charcoal， Mianmaguanzhong （Clematis Armandii） Charcoal， and Oujie （Nelumbo Nucifera） Charcoal.

BackgroundExecutive function deficits constitute a core problem in attention-deficit/hyperactivity disorder （ADHD）. Previous assessments of executive function in children with ADHD have predominantly relied on performance-based neuropsychological tests conducted in laboratory settings， though their predictive validity for real-world functional outcomes remains limited. In contrast， ecological executive function emphasizes the evaluation of complex task management in naturalistic contexts， demonstrating a stronger predictive power for functional adaptation in daily living among children with ADHD， such as multitasking performance， social interactions and so on. However， current empirical evidence regarding ecological executive function in this population remains insufficient. ObjectiveTo investigate the executive function characteristics of children with ADHD from an ecological perspective， thereby providing references for developing targeted interventions. MethodsA case control study was conducted， including 277 ADHD children who met the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） criteria and were selected at the Child Health Care and Mental Health Center of Shenzhen Children's Hospital from June 2017 to December 2020， as well as 98 healthy controls were recruited from primary and secondary schools in Shenzhen. All participants were assessed using Wechsler Intelligence Scale for Children， fourth edition （WISC-IV） and Behavior Rating Inventory of Executive Function （BRIEF）. Differences in WISC-IV and BRIEF scores were compared between ADHD group and control groups， followed by the comparison of BRIEF scores by gender and ADHD subtypes. ResultsAmong the 277 children with ADHD， 136 cases （49.10%） had predominantly inattentive type （ADHD-I）， 6 cases （2.17%） had predominantly hyperactive-impulsive type （ADHD-HI）， and 135 cases （48.73%） had combined type （ADHD-C）. ADHD group demonstrated significantly lower scores on both the WISC-IV total IQ and four index scores （verbal comprehension， perceptual reasoning， working memory and processing speed） than control group （t=3.698~9.335， P<0.01）. After controlling for WISC-IV total IQ as a covariate， the scores of each factor in the dimensions of behavioral regulation index （inhibition， shifting， emotional control） and metacognition index （task initiation， working memory， planning， monitoring and organization） were all higher in ADHD group than in control group， and the differences were statistically significant （F=46.563~290.475， P<0.01）. In terms of gender， no statistically significant difference was found in BRIEF composite scores （behavioral regulation index or metacognition index） of children with ADHD （t=0.105~1.190， P>0.05）. In terms of ADHD subtypes， children with ADHD-C reported significantly higher scores than those with ADHD-I on the scores of inhibition， emotional control， organization and monitoring in BRIEF （t=2.481~7.343， P<0.05 or 0.01）. ConclusionChildren with ADHD have multidimensional deficits in ecological executive function， which vary across different subtypes. ［Funded by Shenzhen Excellent Science and Technology Innovation Talent Training Project （number， RCYX20221008092849069）； the Sanming Project of Medicine in Shenzhen］

Multiple myeloma (MM) is a hematological malignancy that poses significant treatment challenges due to its heterogeneity and propensity for relapse and progression. In the last two decades, the therapeutic landscape of MM has changed dramatically, but the disease remains largely incurable, with many patients facing treatment resistance. This review evaluates the current status of MM treatments, emphasizing the limitations of traditional therapies and the emerging role of immunotherapy in improving patient outcomes. It highlights the importance of achieving and maintaining minimal residual disease negativity and a balanced immune response as key treatment goals. Furthermore, it discusses the advancements in immunotherapies that are improving the prospects for patients, particularly those with relapsed or refractory disease. Innovative strategies, such as chimeric antigen receptor T-cell therapy, bispecific antibodies, and bispecific T cell engagers, have shown significant promise by targeting the malignant cells and the bone marrow microenvironment, which are essential for disease persistence and resistance to therapy. Future research should focus on refining MM treatment strategies, including the integration of immunotherapy into earlier treatment lines and the development of predictive biomarkers for personalized treatment approaches, ultimately enhancing patient outcomes.

Targeted covalent inhibitors, primarily targeting cysteine residues, have attracted great attention as potential drug candidates due to good potency and prolonged duration of action. However, their discovery is challenging. In this research, a database-assisted liquid chromatography-tandem mass spectrometry (LC-MS/MS) strategy was developed to quickly discover potential cysteine-targeting compounds. First, compounds with potential reactive groups were selected and incubated with N-acetyl-cysteine in microsomes. And the precursor ions of possible cysteine-adducts were predicted based on covalent binding mechanisms to establish in-house database. Second, substrate-independent product ions produced from N-acetyl-cysteine moiety were selected. Third, multiple reaction monitoring scan was conducted to achieve sensitive screening for cysteine-targeting compounds. This strategy showed broad applicability, and covalent compounds with diverse structures were screened out, offering structural resources for covalent inhibitors development. Moreover, the screened compounds, norketamine and hydroxynorketamine, could modify synaptic transmission-related proteins in vivo, indicating their potential as covalent inhibitors. This experimental-based screening strategy provides a quick and reliable guidance for the design and discovery of covalent inhibitors.

Objective To study the initial pumping speed of sodium citrate in single plasma exchange with regional citrate anticoagulation(RAC).Methods From January to December 2021,15 patients and 67 times of treatment with local sodium citrate anticoagulation single plasma exchange in the hospital were in-cluded in the study.According to the initial pumping speed of sodium citrate,they were included in the low-speed group(n=33)and the high-speed group(n=34).The transmembrane pressure,filter pressure drop and venous pressure were compared between the two groups at 30 minutes,one hour and two hours after treatment.The free calcium concentration after plasma separator at 15 minutes and one hour after treatment,and the coagulation of plasma separator and extracorporeal circulation pipeline at the end of treatment were compared between the two groups.The concentration of free calcium,blood gas analysis and electrolyte were compared at the beginning of treatment,one hour after treatment and at the end of treatment.Results The free calcium concentration after the filter was monitored at 15 minutes and one hour of treatment in both groups was within the effective range of anticoagulation recommended by the guidelines.There were no lips,fingertip numbness and hand-foot convulsions in the two groups during the treatment,and no bleeding oc-curred after the treatment.There were four cases of hypocalcemia and two cases of alkalosis in the low-speed group,and 13 cases of hypocalcemia and eight cases of alkalosis in the high-speed group.The difference be-tween the two groups was statistically significant(P＜0.05).There were 15 cases of grade Ⅰ coagulation and five cases of grade Ⅱ coagulation in plasma separator and pipeline in the low-speed group,while there were 14 cases of grade Ⅰ coagulation and four cases of grade Ⅱ coagulation in plasma separator and pipeline in the high-speed group.There was no significant difference between the two groups(P＞0.05).Conclusion In plasma exchange treatment,according to the low initial pumping speed,RAC can not only ensure the anticoagulant effect,but also reduce the incidence of complications such as hypocalcemia and alkalosis.

OBJECTIVE To explore the effect mechanism of Eucommia ulmoides on improving postpartum depression in rats. METHODS Pregnant rats were randomly divided into normal group， postpartum depression group， and low-dose and high-dose groups of E. ulmoides （1.34， 2.68 g/kg， calculated by crude drug）， with 10 rats in each group. Except for the normal group， the rats in other groups suffered from fear stress to induce postpartum depression model during pregnancy； at the same time of modeling， the administration groups were given relevant medicine intragastrically， while the normal group and postpartum depression group were given physiological saline intragastrically for 21 days. Postpartum behaviors of rats during the experiment were assessed using the open field test， Morris water maze test and sucrose preference test. Additionally， the levels of corticosterone （CORT） in serum， corticotropin releasing factor （CRF） and urocortin （UCN） in hypothalamus， and adrenocorticotropic hormone （ACTH） in hypophysis were detected； meanwhile， the protein expressions of CRF receptor 1 （CRFR1）， CRFR2， and voltage-dependent anion channel 1 （VDAC1） in hippocampal tissue were measured； the proportions of apoptotic cells and JC-1 high potential cells in hippocampal tissue were determined， and the morphology of hippocampal tissue was observed. RESULTS Compared with postpartum depression group， the high-dose group of E. ulmoides showed improvements in appetite， mental state， and hair color in rats； their body weight had increased； the scores of vertical movement， horizontal movement and self-sorting significantly increased； from the 2ed to 4th day avoidance latency significantly shortened， and the times of crossing the platform and the time of crossing the platform Δ 基金项目国家自然科学基金青年基金项目（No.82204789） significantly increased/prolonged （P＜0.05）； the ratio of glucose and water consumption significantly increased at 20 days of pregnancy and 30 days postpartum （P＜0.05）； the levels of CRF， UCN， ACTH and CORT， phagocytic rate， protein expressions of CRFR2 and VDAC1， and the proportion of apoptosis cells in hippocampal tissue were decreased significantly （P＜0.05）； the proportion of JC-1 high potential cells significantly increased （P＜0.05）， and the phenomenon of edema around neuronal cells was significantly improved. CONCLUSIONS E. ulmoides can improve postpartum depression by inhibiting excessive activation of hypothalamic-pituitary-adrenal axis， decreasing the expression of CRFR2， thereby inhibiting the expression of VDAC1， and decreasing the apoptosis of neuronal cells.

OBJECTIVE To explore the effect mechanism of Eucommia ulmoides on improving postpartum depression in rats. METHODS Pregnant rats were randomly divided into normal group， postpartum depression group， and low-dose and high-dose groups of E. ulmoides （1.34， 2.68 g/kg， calculated by crude drug）， with 10 rats in each group. Except for the normal group， the rats in other groups suffered from fear stress to induce postpartum depression model during pregnancy； at the same time of modeling， the administration groups were given relevant medicine intragastrically， while the normal group and postpartum depression group were given physiological saline intragastrically for 21 days. Postpartum behaviors of rats during the experiment were assessed using the open field test， Morris water maze test and sucrose preference test. Additionally， the levels of corticosterone （CORT） in serum， corticotropin releasing factor （CRF） and urocortin （UCN） in hypothalamus， and adrenocorticotropic hormone （ACTH） in hypophysis were detected； meanwhile， the protein expressions of CRF receptor 1 （CRFR1）， CRFR2， and voltage-dependent anion channel 1 （VDAC1） in hippocampal tissue were measured； the proportions of apoptotic cells and JC-1 high potential cells in hippocampal tissue were determined， and the morphology of hippocampal tissue was observed. RESULTS Compared with postpartum depression group， the high-dose group of E. ulmoides showed improvements in appetite， mental state， and hair color in rats； their body weight had increased； the scores of vertical movement， horizontal movement and self-sorting significantly increased； from the 2ed to 4th day avoidance latency significantly shortened， and the times of crossing the platform and the time of crossing the platform Δ 基金项目国家自然科学基金青年基金项目（No.82204789） significantly increased/prolonged （P＜0.05）； the ratio of glucose and water consumption significantly increased at 20 days of pregnancy and 30 days postpartum （P＜0.05）； the levels of CRF， UCN， ACTH and CORT， phagocytic rate， protein expressions of CRFR2 and VDAC1， and the proportion of apoptosis cells in hippocampal tissue were decreased significantly （P＜0.05）； the proportion of JC-1 high potential cells significantly increased （P＜0.05）， and the phenomenon of edema around neuronal cells was significantly improved. CONCLUSIONS E. ulmoides can improve postpartum depression by inhibiting excessive activation of hypothalamic-pituitary-adrenal axis， decreasing the expression of CRFR2， thereby inhibiting the expression of VDAC1， and decreasing the apoptosis of neuronal cells.

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1^-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Animals ; Humans ; Mice ; Rats ; Bone Remodeling/physiology* ; Caspase 1 ; Periodontal Ligament ; Pyroptosis ; Tooth Movement Techniques

Objective To investigate the relationship between aspartate aminotransferase-platelet ratio index(APRI)and hepatocellular carcinoma(HCC)recurrence after radiofrequency ablation(RFA),and to construct a nomogram model for predicting the prognosis.Methods The clinical data of a total of 204 patients,whose initial diagnosis was HCC and received RFA at the Wujin Hospital Affiliated to Jiangsu University of China between January 2017 and December 2020,were retrospectively analyzed.The optimal cut-off value of APRI was determined using receiver operating characteristic(ROC)curve.Kaplan-Meier curves were plotted to estimate the recurrence-free survival(RFS)of high-APRI group patients and low-APRI group patients.The independent predictors of HCC recurrence after RFA were identified by using univariate and multivariate Cox regression analysis,and significant variables were selected to construct a nomogram model.The predictive ability of the nomogram model for HCC recurrence was evaluated by the consistency index(C-index)and calibration curves.Results The incidence of HCC recurrence after RFA was 57.4%(117/204),the optimal cut-off value of APRI for predicting HCC recurrence was 0.501,and the area under curve(AUC)value was 0.678(95%CI=0.603-0.752).High-APRI group(≥0.501)had 121 patients and low-APRI group(＜0.501)had 83 patients.High APRI index was significantly correlated with low RFS(χ2=12.929,P＜0.01).The univariate and multivariate Cox regression analysis revealed that the number of tumors(HR=1.541,95%CI=1.039-2.286,P=0.031),maximum tumor diameter(HR=1.461,95%CI=1.011-2.112,P=0.044),serum AFP level(HR=2.286,95%CI=1.576-3.318,P＜0.01)and APRI index(HR=1.873,95%CI=1.257-2.790,P=0.002)were the independent risk factors for HCC recurrence.Based on the above four variables,a nomogram model for predicting HCC recurrence after RFA was constructed,the C-index was 0.769(95%CI=0.676-0.862),and the AUC values for 1-,2-,and 3-year RFS prediction were 0.707,0.719,and 0.707,respectively.The calibration curves showed that a good consistency existed between the predicted probability and actual probability.Conclusion The nomogram model based on APRI and tumor biological characteristics has an excellent predictive ability for HCC recurrence after RFA.(J Intervent Radiol,2024,32:38-43)