Objective To explore the key environmental factors influencing the distribution and spatially stratified heterogeneity of the suitable habitats of Ranunculus ternatus Thunb.;To predict its potential suitable habitats within China;To provide theoretical guidance for the conservation of its wild resources,artificial introduction and cultivation,and production planning.Methods Based on the MaxEnt model,a distribution prediction model was established using 148 selected species distribution information and 28 environmental factor data.The ENMeval package in R language was used to optimize the model parameters.Quantitative analysis(q-value ranking)of environmental factors affecting spatial differentiation in potential suitable areas using geographic detector factor detection and interaction detection.Results After optimization,the accuracy of model was improved and the degree of overfitting was reduced.The average value of the area under the curve(AUC)was 0.940.The contribution rate of environmental factors and the jackknife test showed that the key environmental factors influencing the distribution of Ranunculus ternatus Thunb.mainly included the precipitation in March,the precipitation in November,elevation,the solar radiation intensity in October,the solar radiation intensity in December,and the average temperature in January.The results of raster calculation showed that the area of highly suitable habitats of Ranunculus ternatus Thunb.was approximately 4.105×104 km2,the area of moderately suitable habitats was approximately 4.243×105 km2,and the area of lowly suitable habitats was approximately 6.385×105 km2,accounting for about 3.8%,38.4%and 57.8%of the total area of suitable habitats,respectively.Conclusion This study can provide a basis for the conservation and sustainabele utilization of the wild resources of Ranunculus ternatus Thunb.

Deutetrabenazine(DTBZ)is a selective oral small molecule inhibitor of vesicular monoamine transporter 2(VMAT2).Its pharmacological action works by inhibiting VMAT2,thereby reducing the release of presynaptic dopamine and alleviating tardive dyskinesia symptoms caused by long-term use of dopamine receptor antagonists.Compared with tetrabenazine,DTBZ has longer half-life,lower peak plasma concentration,and smaller plasma concentration fluctuations.Clinical studies demonstrate that DTBZ significantly improves abnormal involuntary movement in patients with tardive dyskinesia and has a favourable safety profile.Based on available clinical evidence and practical experience,this paper discuss the common questions about DTBZ including the suitable population,dose,duration of treatment,combination administration with antipsychotics,efficacy assessment and application in special populations.This article aimed to provide guidance and recommendations on clinical application of DTBZ for clinicians.

Schizophrenia is a chronic and debilitating mental disorder.Around 20%to 40%of patients do not respond well to normal antipsychotic medication,and are ultimately diagnosed with treatment-resistant schizophrenia(TRS),representing the most severe and challenging form of schizophrenia.Currently,clozapine is the standard treatment for TRS.Early identification and standardized treatment can be beneficial to patients with TRS by controlling acute-phase symptoms as soon as possible,reducing suicidal rate and improving their quality of life.Under the guidance of the Steering Committee,this consensus was formed after multiple discussions by 30 psychiatric experts and anonymous Delphi surveys including 17 consensus opinions on treatment-resistant schizophrenia,which cover risk factors and prevention,diagnosis and evaluation,standardized clozapine treatment and management of adverse reactions,treatment regimens for clozapine resistance and intolerance,and psychosocial intervention,etc.The consensus-making process also incorporated evidence-based medicine to help standardize and guide diagnosis and treatment for adults with TRS in China.

Objective:To develop and validate machine learning models for predicting the cumulative live birth rate (CLBR) following in vitro fertilization (IVF) and to analyze key predictive features using SHAP values. Methods:This retrospective study included data from patients who underwent IVF-embryo transfer at the Department of Reproductive Medicine, Baoding Maternal and Child Health Hospital, between January 2017 and December 2022. Patients were categorized into two groups based on live birth outcome: the live birth group ( n=1 036) and the non-live birth group ( n=756). The dataset was randomly divided into a training set and a validation set in a ratio of 7∶3. Five algorithms were utilized for model development: logistic regression, random forest, extreme gradient boosting (XGBoost), support vector machine, and neural networks. Model performance was assessed using the area under the receiver operating characteristic (AUC) curve, F1 score, and calibration curves. Clinical decision curve analysis (DCA) was employed to evaluate the clinical utility of the models. SHAP values were used to interpret feature importance in the XGBoost model and enhance its explainability. Results:The XGBoost model demonstrated the best performance in predicting CLBR,with accuracy of 72.44%, AUC of 0.775, and F1 score of 0.654, accuracy and F1 score outperforming logistic regression (accuracy was 70.02%, F1 score was 0.585), random forest (accuracy was 71.69%, F1 score was 0.606), support vector machine (accuracy was 70.20%, F1 score was 0.607), and neural network (accuracy was 68.72%, F1 score was 0.560). The calibration curve of XGBoost closely aligned with the diagonal line, indicating that the predicted probabilities were very close to the actual outcomes, demonstrating good calibration. DCA indicated that the XGBoost model provided higher net benefits across a wide range of clinical decision thresholds. SHAP value analysis identified number of previous IVF failures, antral follicle count, anti-Müllerian hormone level, percentage of normal sperm morphology, and sperm DNA fragmentation index as key predictors of CLBR.Conclusion:The XGBoost model exhibits excellent predictive performance and calibration for CLBR, with SHAP values providing important insights into feature importance. This model has the potential to support the development of personalized treatment strategies in clinical practice. However, its generalizability needs to be validated using external datasets to ensure its applicability to diverse populations.

Blonanserin,a second-generation atypical antipsychotic agent,acts as an antagonist for dopamine D2,D3,and serotonin 5-HT2A receptors.Clinical studies have demonstrated that blonanserin is non-inferior to other antipsychotics,such as haloperidol and risperidone,in alleviating the symptoms of schizophrenia.Moreover,it exhib-its beneficial effects on cognitive symptoms and social functioning,with a favorable safety profile,making it one of the key treatment options for schizophrenia.With extensive clinical experience accumulated in China,this expert consensus aims to provide psychiatrists with updated and localized guidance on the optimal use of blonan-serin.Based on a systematic review of the latest evidence-particularly studies in Chinese population,this paper pres-ents the updated Chinese expert recommendations for the clinical use of blonanserin in 2024.

Objective To analyze the clinical characteristics and explore the potential mechanisms under-lying acute wheezing associated with respiratory syncytial virus(RSV)and human rhinovirus(HRV)infections in infants.Methods A retrospective analysis was conducted on 560 infants who consecutively presented to the emer-gency department of Qingdao University Affiliated Women and Children's Hospital between January 2022 and December 2024 with acute exacerbation of wheezing caused by RSV and/or HRV infection;these infants constituted the infection group.A control group of 120 healthy infants who underwent routine physical examinations at the same hospital during the same period was also included.Multiplex PCR amplification sequencing technology was employed to detect respiratory pathogens via nucleic acid analysis.The infection group was further classified into the RSV-only group(n=248),the HRV-only group(n=186),and the co-infection group(HRV+RSV,n=126).One-way analysis of variance(ANOVA)was used to compare body mass index(BMI),peripheral blood white blood cell(WBC)count,neutrophil count,lymphocyte count,C-reactive protein(CRP)levels,and concentrations of interleukin(IL)-1β,IL-6,Toll-like receptor 4(TLR4),NOD-like receptor protein 3(NLRP3)inflamma-some,and matrix metalloproteinase-9(MMP-9)across the groups.Additionally,comparisons were made regarding gender distribution,severity of wheezing,history of wheezing,history of eczema,parental allergic history,oxygen supplementation requirements,and presence of concurrent pulmonary infection among the infected infants.Based on wheezing severity,the infection group was further divided into a severe wheezing group and a mild wheezing group.Clinical characteristics and biological indicators were analyzed and compared between these two groups to identify potential independent risk factors.Pearson correlation analysis was performed to evaluate the association between peripheral blood levels of IL-6,NLRP3,and MMP-9 and the severity of acute wheezing exacerbation in children.Results A one-way ANOVA indicated statistically significant differences in WBC count,neutrophil count,CRP,IL-1β,IL-6,TLR4,NLRP3,and MMP-9 levels across the study groups(all P<0.001).Both the RSV and co-infection groups demonstrated significantly higher rates of severe wheezing,oxygen requirement,and prolonged wheezing duration compared to the HRV group(all P<0.05).Among these,the co-infection group exhibited the highest oxygen requirement rate,although the duration of wheezing was shorter than that observed in the RSV group(P<0.05).The incidence of concurrent pulmonary infection was significantly greater in the RSV group compared to the HRV group(P<0.05).Additionally,the proportion of infants with a prior history of wheez-ing was significantly higher in the RSV group than in both the HRV and co-infection groups(P<0.05).Both the RSV and co-infection groups showed a significantly higher prevalence of eczema history among infants compared to the HRV group(P<0.05).Moreover,the co-infection group had a significantly higher proportion of parental allergic history compared with both the RSV and HRV groups(P<0.05).Clinical data analysis stratified by wheezing severity revealed that RSV was the most commonly detected virus among the enrolled infants,particularly in those presenting with severe wheezing(χ2=3.940,P=0.002).The severe wheezing group exhibited significantly higher rates of prior wheezing,history of eczema,parental allergy,need for oxygen supplementation,and concurrent pulmonary infections compared to the mild wheezing group(P<0.001).Furthermore,the duration of wheezing was significantly prolonged in the severe group relative to the mild group(t=2.058,P=0.040).Levels of IL-6,NLRP3,and MMP-9 were also significantly elevated in the severe wheezing group(P<0.05).Multivariate logistic regression analysis revealed that RSV infection,along with elevated levels of IL-6,NLRP3,and MMP-9,were independent risk factors associated with severe wheezing(OR=3.217,1.023,1.022,and 1.056,respectively;all P<0.05).In children with RSV/HRV infection,the severity of acute wheezing demonstrated a positive correlation with NLRP3 and MMP-9 levels(P<0.05).The Pearson correlation coefficient between NLRP3 and MMP-9 was r=0.238(P<0.001),indicating a weak yet statistically significant positive relationship.Conclusions RSV may provoke more severe respiratory inflammatory responses and clinical manifestations compared to HRV.Individuals with a genetic predisposition to allergies or a pre-existing history of respiratory conditions may experience height-ened severity of wheezing following viral infection.The NLRP3 inflammasome may further intensify airway inflam-mation and remodeling through the promotion of MMP-9 release.These mechanisms may collectively contribute to the pathogenesis of acute wheezing episodes and subsequently influence the progression of respiratory diseases.

Objective:To develop and validate machine learning models for predicting the cumulative live birth rate (CLBR) following in vitro fertilization (IVF) and to analyze key predictive features using SHAP values. Methods:This retrospective study included data from patients who underwent IVF-embryo transfer at the Department of Reproductive Medicine, Baoding Maternal and Child Health Hospital, between January 2017 and December 2022. Patients were categorized into two groups based on live birth outcome: the live birth group ( n=1 036) and the non-live birth group ( n=756). The dataset was randomly divided into a training set and a validation set in a ratio of 7∶3. Five algorithms were utilized for model development: logistic regression, random forest, extreme gradient boosting (XGBoost), support vector machine, and neural networks. Model performance was assessed using the area under the receiver operating characteristic (AUC) curve, F1 score, and calibration curves. Clinical decision curve analysis (DCA) was employed to evaluate the clinical utility of the models. SHAP values were used to interpret feature importance in the XGBoost model and enhance its explainability. Results:The XGBoost model demonstrated the best performance in predicting CLBR,with accuracy of 72.44%, AUC of 0.775, and F1 score of 0.654, accuracy and F1 score outperforming logistic regression (accuracy was 70.02%, F1 score was 0.585), random forest (accuracy was 71.69%, F1 score was 0.606), support vector machine (accuracy was 70.20%, F1 score was 0.607), and neural network (accuracy was 68.72%, F1 score was 0.560). The calibration curve of XGBoost closely aligned with the diagonal line, indicating that the predicted probabilities were very close to the actual outcomes, demonstrating good calibration. DCA indicated that the XGBoost model provided higher net benefits across a wide range of clinical decision thresholds. SHAP value analysis identified number of previous IVF failures, antral follicle count, anti-Müllerian hormone level, percentage of normal sperm morphology, and sperm DNA fragmentation index as key predictors of CLBR.Conclusion:The XGBoost model exhibits excellent predictive performance and calibration for CLBR, with SHAP values providing important insights into feature importance. This model has the potential to support the development of personalized treatment strategies in clinical practice. However, its generalizability needs to be validated using external datasets to ensure its applicability to diverse populations.

OBJECTIVE To evaluate the quality differences of Alpinia katsumadai from different habitats. METHODS High- performance liquid chromatography（HPLC） was used to establish the fingerprints of A. katsumadai from 18 batches of different habitats， and the quality of A. katsumadai from different habitats was comprehensively evaluated by similarity evaluation， cluster analysis （CA）， principal component analysis （PCA）， orthogonal partial least squares-discriminant analysis （OPLS-DA） and the content determination results of alpinetin， pinocembrin， cardamonin and alnustone in A. katsumadai. RESULTS The similarity of HPLC fingerprints for 18 batches of A. katsumadai was ＞0.9. Eleven common peaks were identified from the chromatogram， and four of them were specifically characterized. Both CA and PCA grouped 18 batches of A. katsumadai into 3 categories， extracting 2 principal components （the cumulative variance contribution rate reached 89.798%）. OPLS-DA identified 9 quality difference markers， namely the components corresponding to peaks 4， 9， 3， 2， 7 （pinocembrin）， 8 （cardamonin）， 6 （alpinetin）， 10 and 11 （alnustone）. The content of alpinetin， pinocembrin， cardamonin， and alnustone ranged from 4.507 1-11.579 7， 5.154 4-14.183 3， 5.109 5-13.588 3 and 4.494 6-11.277 2 mg/g， respectively. CONCLUSIONS The quality of A. katsumadai from different habitats is quite different， and the quality of A. katsumadai from Hainan is the best.

OBJECTIVE To explore the mechanism of Huayu jiedu formula in regulating inflammatory injury in chronic kidney disease （CKD）. METHODS Fifty male SD rats were randomly divided into a sham surgery group （10 rats） and a modeling group （40 rats）. The CKD model was replicated in the modeling group by unilateral ureteral obstruction surgery. After successful modeling， the rats were randomly divided into model group， esaxerenone group （positive control）， and TCM low- and high-dose groups， with 10 rats in each group. The Esaxerenone group was given 1 mg/kg of esaxerenone， while the TCM low- and high-dose groups were given 13.7 and 27.4 g/kg of Huayu jiedu formula respectively， the sham surgery group and model group were given an equal volume of physiological saline， all groups were intervened continuously for 14 days. Hematoxylin eosin and Masson staining were used to observe the pathological changes in rat kidney tissue. Conventional biochemical methods were used to detect serum urea （SUr）， serum creatinine （SCr）， malondialdehyde （MDA）， and superoxide dismutase （SOD） levels； enzyme-linked immunosorbent assay was used to detect the levels of serum interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α（TNF-α）； immunohistochemistry and Western blot were used to detect the protein expression of peroxisome proliferator-activated receptor γ coactivator-1α（PGC-1α） ， mitochondrial transcription factor A （TFAM）， absent in melanoma 2（AIM2）， caspase-1， gasdermin D （GSDMD）， IL-1β and IL-18 in renal tissue； real-time fluorescence quantitative PCR was used to detect the mRNA expression of AIM2. RESULTS Compared with the sham surgery group， the renal tissue of the model group showed pathological changes such as glomerular deformation and destruction， severe tubular dilation， and increased deposition of blue fibrin； the levels of SUr， SCr， MDA， IL-1β， IL-6， TNF-α，the protein expression of AIM2， GSDMD， caspase-1， IL-1β， IL-18 ， and the mRNA expression of AIM2 were significantly increased or up-regulated （P＜0.01）； the levels of SOD， the protein expression of PGC-1α， TFAM were significantly reduced or down-regulated （P＜0.01）. Compared with the model group， all treatment groups showed improvement in the above symptoms and most indicators in rats. CONCLUSIONS Huayu jiedu formula may improve renal function， alleviate renal inflammatory damage and pyroptosis， and exert renal protective effects by regulating the AIM2 pyroptosis pathway.

BACKGROUND: The level of measurable residual disease (MRD) before and after transplantation is related to inferior transplant outcomes, and post-hematopoietic stem cell transplantation measurable residual disease (post-HSCT MRD) has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease (pre-HSCT MRD). However, only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia (ALL). This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 1683 ALL patients from Peking University People's Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariable analysis was performed to determine independent influencing factors from the univariable analysis. RESULTS: Both in total patients and in T-cell ALL or B-cell ALL, pediatric or adult, human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups, positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity ( P  <0.001 for all). Disease status (complete remission 1 [CR1] vs . ≥CR2) was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL, pediatric, or haploidentical SCT subgroups ( P  = 0.027; P  = 0.003; P  = 0.035; P  = 0.003, respectively). A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status. The cumulative incidence of post-HSCT MRD positivity was 12.3%, 25.1%, and 38.8% for subjects with scores of 0, 1, and 2-3, respectively ( P  <0.001). Multivariable analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival. CONCLUSION Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology* ; Neoplasm, Residual ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; Risk Factors ; Adolescent ; Adult ; Child ; Child, Preschool ; Young Adult ; Middle Aged ; Infant ; Transplantation, Homologous ; Proportional Hazards Models ; Retrospective Studies