ObjectiveTo evaluate the effectiveness of exhalation-inhalation exercise on early pulmonary rehabi-litation for patients with acute exacerbation of chronic obstructive pulmonary disease （AECOPD）. MethodsA total of 120 participants with AECOPD were randomly divided into a treatment group and a control group， with 60 participants in each group. The control group treated with conventional western medicine， while the treatment group received exhalation-inhalation exercise training on the basis of conventional western medicine treatment， with 30 minutes per session and 5 sessions per week. The course of treatment for both groups was 12 weeks. The primary outcome was the 6-minute walking distance （6MWD）. The secondary outcomes included pulmonary function indexes including forced expiratory volume in one second/forced vital capacity （FEV1/FVC）， percentage of predicted forced expiratory volume in one second （FEV1%） and percentage of predicted forced vital capacity （FVC%）， St.George's Respiratory Questionnaire （SGRQ） score， modified Medical Research Council （mMRC） dyspnea scale score， COPD assessment test （CAT） score， hospital anxiety and depression scale-anxiety subscale ［HADS（A）］ score， and hospital anxiety and depression scale-depression subscale ［HADS（D）］ score. Meanwhile， safety of all participants was recorded and assessed. ResultsDuring the treatment， 12 participants dropped out from both the treatment group and the control group， with 48 participants in each group finally included in the analysis. The 6MWD of both groups after treatment was higher than that before treatment， and the 6MWD of the treatment group was higher than that of the control group （P＜0.05 or P＜0.01）. After treatment， the SGRQ score， mMRC score and CAT score of the treatment group were lower than those before treatment， while FEV1%， FVC% and FEV1/FVC were higher than those before treatment （P＜0.05）. Moreover， after treatment， the FEV1/FVC of the treatment group was higher than that of the control group， while the SGRQ score， mMRC score and CAT score were lower than those of the control group （P＜0.05 or P＜0.01）. There was no statistically significant difference in pulmonary function indexes， SGRQ score， mMRC score and CAT score after treatment in the control group （P＞0.05）. No statistically significant difference was observed in HADS（A） score and HADS（D） score after treatment within and between groups （P＞0.05）. The incidence of adverse reactions in the treatment group was 6.25% （3/48）， and 0 in the control group， with no statistically significant difference between groups （P＞0.05）. ConclusionExhalation-inhalation exercise for patients with AECOPD in early pulmonary rehabilitation can improve patients' exercise tole-rance， quality of life， clinical symptoms and pulmonary function， with good safety.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

OBJECTIVES: To clarify the role of hippocampal glutamate system in regulating HPA axis in mediating the effect of electroacupuncture (EA) at the heart meridian for improving myocardial injury in rats with acute myocardial ischemia (AMI). METHODS: Male SD rats were randomized into sham-operated group, AMI group, EA group, and L-glutamic acid+EA group (n=9). Rat models of AMI were established by left descending coronary artery ligation, and EA was applied at the "Shenmen-Tongli" segment; the rats in L-glutamic acid+EA group were subjected to microinjection of L-glutamic acid into the bilateral hippocampus prior to AMI modeling and EA treatment. Cardiac functions of the rats were evaluated using echocardiography, and ECG and heart rate variation (HRV) were analyzed using PowerLab and LabChart. Pathological changes in the myocardial tissue was examined using HE staining, and serum levels of myocardial enzymes were detected with ELISA. Myocardial expressions of TH and GAP43 were detected with immunohistochemistry, and colocalization of VGLUT1, VGLUT2 and c-fos were observed using immunofluorescence staining; the expressions of VGLUT1, VGLUT2, NMDAR1 and NMDAR2B were detected using Western blotting. RESULTS: The rat models of AMI showed significantly decreased LVEF and LVFS and increased serum levels of myocardial enzymes in positive correlation with the HPA axis. Numerous TH- and GAP43-positive cells were observed in the hippocampus, where the expressions of NE and E, neurons colabeled with VGLUT1, VGLUT2 and c-fos, and expressions of VGLUT1, VGLUT2, NMDAR1, NMDAR2B and Glu increased significantly. All these changes were significantly improved by interventions with EA as compared with those in AMI and L-Glutamate+EA groups. CONCLUSIONS In rats with AMI, EA at the heart meridian can regulate excessive glutamate release in the hippocampus, thereby inhibiting HPA axis hyperactivity and reducing sympathetic nerve activity to protect the myocardial tissue.
Animals ; Electroacupuncture ; Male ; Rats, Sprague-Dawley ; Hippocampus/metabolism* ; Rats ; Glutamic Acid/metabolism* ; Myocardial Ischemia/physiopathology* ; Hypothalamo-Hypophyseal System/physiopathology* ; Pituitary-Adrenal System/physiopathology* ; Receptors, N-Methyl-D-Aspartate/metabolism*

BACKGROUND: Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC. METHODS: A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms. RESULTS: Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC. CONCLUSIONS This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.

Breast cancer patients in China tend to be diagnosed at a younger age, making fertility issues a significant clinical and societal challenge. Current evidence indicates that the fertility rate among breast cancer survivors is substantially lower than that of the general population of the same age. Both the disease itself and anti-tumor treatments-including chemotherapy, radiotherapy, endocrine therapy, targeted therapy, and immunotherapy-can adversely affect female fertility. Therefore, fertility considera-tions should be integrated into the comprehensive management of breast cancer from the time of diagnosis. Several guidelines and consensus statements have been established to direct fertility management in these patients. Clinical practice has achieved some success in fertility preservation through pharmacological, surgical, and assisted reproductive technologies, which help mitigate treatment-related damage to fertility. Nevertheless, further progress relies on multidisciplinary collaboration, particularly in addressing the ethical and legal aspects of fertility preservation. Recent advances in research on hereditary breast cancer, risk assessment, and preimplantation genetic testing for polygenic diseases offer new perspectives and directions for fertility management in breast cancer patients. This review systematically summarizes the current fertility status, existing management strategies, and cutting-edge research on healthy reproduction in breast cancer patients, with the aim of supporting the standardization of fertility management protocols.

OBJECTIVES: Multiple myeloma (MM) is a highly heterogeneous hematologic malignancy, with disease progression driven by cytogenetic abnormalities and a complex bone marrow microenvironment. This study aims to construct a prognostic model for MM based on transcriptomic data and lipid metabolism related genes (LRGs), and to identify potential drug targets for high-risk patients to support clinical decision-making. METHODS: In this study, 2 transcriptomic datasets covering 985 newly diagnosed MM patients were retrieved from the Gene Expression Omnibus (GEO) database. Univariate Cox regression and 101 machine learning algorithms were used for gene selection. An LRG-based prognostic model was constructed using Stepwise Cox (both directions) and random survival forest (RSF) algorithms. The association between the prognostic score and clinical events was evaluated, and model performance was assessed using time-dependent receiver operating characteristic (ROC) curves and the C-index. The added predictive value of combining prognostic scores with clinical variables and staging systems was also analyzed. Differentially expressed genes between high- and low-risk groups were identified using limma and clusterProfiler and subjected to pathway enrichment analysis. Drug sensitivity analysis was conducted using the Genomics of Drug Sensitivity in Cancer (GDSC) database and oncoPredict to identify potential therapeutic targets for high-risk patients. The functional role of key LRGs in the model was validated via in vitro cell experiments. RESULTS: An LRG-based prognostic model (LRG17) was successfully developed using transcriptomic data and machine learning. The model demonstrated robust predictive performance, with area under the curve (AUC) values of 0.962, 0.912, and 0.842 for 3-, 5-, and 7-year survival, respectively. Patients were stratified into high- and low-risk groups, with high-risk patients showing significantly shorter overall survival (OS) and event-free survival (EFS) (both P<0.001) and worse clinical profiles (e.g., lower albumin, higher β2-microglobulin and lactate dehydrogenase levels). Enrichment analysis revealed that high-risk patients were significantly enriched for pathways related to chromosome segregation and mitosis, whereas low-risk patients were enriched for immune response and immune cell activation pathways. Drug screening suggested that AURKA inhibitor BMS-754807 and FGFR3 inhibitor I-BET-762 may be more effective in high-risk patients. Functional assays demonstrated that silencing of key LRG PLA2G4A significantly inhibited cell viability and induced apoptosis. CONCLUSIONS LRGs serve as promising biomarkers for prognosis prediction and risk stratification in MM. The overexpression of chromosomal instability-related and high-risk genetic event-associated genes in high-risk patients may explain their poorer outcomes. Given the observed resistance to bortezomib and lenalidomide in high-risk patients, combination therapies involving BMS-754807 or I-BET-762 may represent effective alternatives.
Humans ; Multiple Myeloma/mortality* ; Prognosis ; Lipid Metabolism/genetics* ; Transcriptome ; Machine Learning ; Male ; Female ; Gene Expression Profiling ; Algorithms

Objective To observe the effect of specialist team-led walking-cognition dual-task train-ing combined with active self-disclosure on control and balance abilities in elderly patients with acute ischemic stroke(AIS).Methods A total of 90 elderly AIS patients treated in our hospital from January 2022 to January 2024 were enrolled and randomly assigned into the control group and the observation group,with 45 cases in each group.The control group received routine walk-ing training,while the observation group received specialist team-led walking-cognition dual-task training combined with active self-disclosure intervention.Control ability,balance ability,walking ability,cognitive function and psychological status were compared between the two groups.Results After intervention,the scores of Sheikh Trunk Control Scale and Fugl-Meyer Assessment(FMA),and the static balance score,dynamic balance score and total score of Berg Balance Scale(BBS)were significantly increased in both the observation and the control groups(P＜0.05),and all above scores were obviously higher in the former group than the latter one(P＜0.01).The two groups also obtained notably shorter single-and dual-task walking time after intervention,but there were no statistical difference in the single-task walking time in both groups before and after intervention(P＞0.05).After intervention,the observation group had significantly shorter dual-task walking time(22.87±7.36 s vs 27.52±8.71 s,P=0.008)and lower walking time cost of dual task[(11.16±4.07)％vs(25.61±7.82)％,P=0.000]when compared with the control group.After intervention,the scores of Mini-Mental Status Examination were increased,and the scores of Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale were decreased in the two groups(P＜0.05).Conclusion Specialist team-led walking-cognition dual-task training com-bined with active self-disclosure intervention can effectively improve trunk control ability,balance ability,walking ability,cognitive function and psychological state in elderly AIS patients,has cer-tian clinical application value.

Objective:To observe the effect of ankle joint proprioception training on ankle joint proprioception, balance and gait in patients with thalamic infarction.Methods:Fifty-six patients with thalamic infarction were divided into a control group and a treatment group, each of 28, using a random number table. Both groups were given conventional lower limb rehabilitation training, but the treatment group was additionally provided with ankle joint proprioception training. Before and after 4 weeks of the treatment, the Tecnobody proprioception testing system was used to determine the average trajectory error rate (ATE) and the time taken in the test. The Berg Balance Scale (BBS) and a balance tester were used to assess balance. A gait analyzer was used to collect spatial-temporal measures of the patients′ walking, including the stride amplitude, stride rate, the proportion of the time spent in the swing phase, and foot dorsiflexion and plantarflexion angles.Results:After the treatment, the time used, ATE, ankle proprioception, BBS scores, static balance test scores, stability limits, stride length, stride rate, swing phase time percentage, and foot dorsiflexion and plantarflexion angles had improved in both groups compared with before the treatment ( P≤0.05). Compared with the control group, the treatment group had a smaller average ATE, spent less time on the ankle proprioception test, had higher BBS scores, had lower scores on the static balance test, had larger limits of stability, took longer strides at a faster rate, and spent a greater percentage of time in the swing phase. That group also showed greater ankle dorsiflexion and plantarflexion on average ( P≤0.05). ATE difference of the affected lower limb and the time to complete the ankle proprioception test were positively correlated with the gap in the static balance ability test, and negatively correlated with the gaps in the BBS score, the limits of stability, stride length, stride rate, and the time share of the swing phase, as well as the dorsiflexion and plantarflexion angles of the foot. Conclusions:Ankle proprioception training, in addition to effectively improving ankle proprioception, can improve the balance and gait of persons with thalamic infarction. It is worthy of clinical application and promotion.

Very-late-onset schizophrenia-like psychosis(VLOSLP)is considered the most common mental disorder in the elderly following dementia and depression, and its clinical symptomatology is different from that of schizophrenia with onset around the average age.The diagnostic classification system and prognosis of VLOSLP are very complicated, and it is still controversial whether it should be classified as a prodromal symptom of dementia or as a type of late-onset schizophrenia.This article reviewed studies concerning the epidemiology, clinical features, diagnosis, prognosis, and neuroimaging of VLOSLP, hoping to provide value as a reference for future clinical research and treatment.