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.

Esophageal carcinoma is a malignant disease with a high incidence rate and poor prognosis. The mitochondrial apoptosis pathway plays a pivotal role in the regulation of cell death and has become a focal point in current cancer therapeutics research. Various active components from traditional Chinese medicine （TCM） can target the mitochondrial apoptosis pathway to inhibit esophageal carcinoma， presenting as potential therapeutic agents for this disease. This paper summarizes relevant research on the inhibition of esophageal carcinoma by active components in TCM via targeting the mitochondrial apoptosis pathway. It has been found that flavonoids （casticin， icariin， luteolin， kaempferol， hesperetin， deguelin， etc.）， terpenoids （oridonin， Jaridonin， artesunate， ethyl acetate fraction of pleurotus ferulatus triterpenoid， etc.）， alkaloids （matrine， swainsonine， etc.）， polyphenols （curcumin， epigallocatechin-3-gallate， corilagin， etc.）， steroids （α-hederin， polyphyllin Ⅵ， etc.）， phenols （optimized scorpion venom peptide CT-K3K7， gecko active polypeptide， etc.）， volatile oils （cinnamaldehyde， α -asarone， etc.） and other active components from TCM can target the intrinsic mitochondrial apoptosis pathway， induce apoptosis in esophageal carcinoma cells， and inhibit their proliferation， invasion and migration by regulating oxidative stress， blocking the cell cycle， regulating signaling pathways such as PI3K/Akt and MAPK.

ObjectiveTo explore the mechanism by which Buyang Huanwutang regulates the glutathione peroxidase 4 （GPX4）-acyl-CoA synthetase long-chain family member 4 （ACSL4） axis to inhibit ferroptosis and promote neurological functional recovery after spinal cord injury （SCI）. MethodsNinety rats were randomly divided into five groups： sham operation group， model group， low-dose Buyang Huanwutang group （12.5 g·kg^-1）， high-dose Buyang Huanwutang group （25 g·kg^-1）， and Buyang Huanwutang + inhibitor group （25 g·kg^-1 + 5 g·kg^-1 RSL3）. The SCI model was established by using the allen method. Tissue was collected on the 7th and 28th days after operation. Motor function was assessed by using the Basso-Beattie-Bresnahan （BBB） scale. Hematoxylin-eosin （HE）， Nissl， and Luxol fast blue （LFB） staining were performed to observe spinal cord histopathology. Transmission electron microscopy was used to examine mitochondrial ultrastructure. Immunofluorescence staining was used to detect the number of NeuN-positive cells and the fluorescence intensity of myelin basic protein （MBP）， GPX4， and ACSL4. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） was used to analyze the mRNA expression of GPX4 and ACSL4. Enzyme linked immunosorbent assay （ELISA） was performed to measure the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD）. Colorimetric assays were used to determine the iron content in spinal cord tissue. ResultsCompared to the sham operation group， the model group exhibited significantly reduced BBB scores （P<0.01）， severe pathological damage in spinal cord tissue， and marked mitochondrial ultrastructural disruption. In addition， the model group showed a decrease in the number of NeuN-positive cells （P<0.01）， reduced fluorescence intensity of MBP and GPX4 （P<0.01）， lower levels of GSH and SOD （P<0.01）， and downregulated mRNA expression of GPX4 （P<0.01）. Moreover， compared to the sham operation group， the model group had elevated levels of ROS， MDA， and tissue iron content （P<0.01）， along with increased fluorescence intensity and mRNA expression of ACSL4 （P<0.01）. Compared with the model group and Buyang Huanwutang + inhibitor group， the Buyang Huanwutang group showed significantly improved BBB scores （P<0.05， P<0.01） and exhibited less severe spinal cord tissue damage， reduced edema and inflammatory cell infiltration， increased neuronal survival， and more intact myelin structures. Additionally， mitochondrial ultrastructure was significantly improved in the Buyang Huanwutang group. Compared to the model group and Buyang Huanwutang + inhibitor group， the Buyang Huanwutang group significantly increased the number of NeuN-positive cells and the fluorescence intensity of MBP （P<0.05， P<0.01）. Furthermore， Buyang Huanwutang significantly increased the fluorescence intensity and mRNA expression of GPX4 （P<0.01） and decreased the fluorescence intensity and mRNA expression of ACSL4 （P<0.01） compared to the model group and Buyang Huanwutang + inhibitor group. Finally， the Buyang Huanwutang group significantly decreased ROS， MDA， and tissue iron content （P<0.01） and significantly increased GSH and SOD levels （P<0.01） compared to the model group and Buyang Huanwutang + inhibitor group. ConclusionBuyang Huanwutang inhibits ferroptosis through the GPX4/ACSL4 axis， reduces secondary neuronal and myelin injury and oxidative stress， and ultimately promotes the recovery of neurological function.

ObjectiveTo investigate the triglyceride-glucose (TyG) index and the level of serum homocysteine (Hcy) in association with the incidence of stroke in type 2 diabetes mellitus (T2DM) patients. MethodsBased on the chronic disease risk factor surveillance cohort in Pudong New Area, Shanghai, excluding those with stroke in baseline survey, T2DM patients who joined the cohort from January 2016 to October 2020 were selected as the research subjects. During the follow-up period, a total of 318 new-onset ischemic stroke patients were selected as the case group, and a total of 318 individuals matched by gender without stroke were selected as the control group. The Cox proportional hazards regression model was used to adjust for confounding factors and explore the serum TyG index and the Hcy biochemical indicator in association with the risk of stroke. ResultsThe Cox proportional hazards regression results showed that after adjusting for confounding factors, the risk of stroke in T2DM patients with 10 μmol·L⁻¹-¹ and Hcy>15 μmol·L⁻¹ was 1.532 times (95%CI: 1.017‒2.309 times, P=0.041) and 1.738 times (95%CI: 1.119‒2.699 times, P=0.014) higher respectively, compared to T2DM patients with Hcy≤10 μmol·L⁻¹. T2DM patients with TyG>9.074 had 1.396 times higher risk of stroke (95%CI: 1.091‒1.787, P=0.008) compared to those with TyG≤9.074. The study found that urea and α1-antitrypsin (α1-AT) were independent risk factors for the incidence of stroke in T2DM patients. For every unit increase in urea andα1-AT, the risk of stroke in T2DM patients increased by 233.6% (HR=3.336, 95%CI: 1.588‒7.009, P=0.001) and 11.3% (HR=1.113, 95%CI: 1.028‒1.205, P=0.008), respectively. Cumulative risk curves showed that Hcy>10 μmol·L⁻¹ and TyG>9.074 accelerated the time to stroke occurrence in T2DM patients. ConclusionElevated levels of Hcy>10 μmol·L⁻¹ and a higher TyG index are risk factors for stroke in T2DM patients. Effective interventions for Hcy and TyG should be conducted for diabetic patients to reduce the incidence of stroke.

Objective:To investigate the effect of "simulated Chinese medicine nursing clinic" teaching on syndrome differentiation ability among nursing students and the teaching effect of this method.Methods:A total of 325 students were randomly divided into conventional teaching group with 163 students (receiving conventional nursing teaching) and real situational teaching group with 162 students (receiving "simulated Chinese medicine nursing nursing clinic" teaching at the same time). A self-made questionnaire for syndrome differentiation-based nursing ability, assessment scores of traditional Chinese medicine nursing theories and skills, and a teaching satisfaction questionnaire were used for evaluation.Results:After intervention, the real situational teaching group (the treatment group and the experience group) had significantly higher socres of syndrome differentiation-based nursing ability (mastery of four diagnostic methods, diagnosis of syndromes, analysis of syndromes, determination of nursing principles, and development of nursing regimens) than the conventional teaching group (the treatment group and the conventional teaching group: 8.97±1.00/8.47±1.20/8.33±1.06/8.30±1.26/7.89±1.13 and 7.96±1.14/7.29±1.36/7.14±1.18/7.39±1.30/7.26±1.18, P<0.05; the experience group and the conventional teaching group: 8.39±1.10/8.17±1.15/8.07±1.06/7.97±1.26/7.73±1.38 and 7.96±1.14/7.29±1.36/7.14±1.18/7.39±1.30/7.26±1.18, P<0.05). The real situational teaching group had a significantly higher overall degree of satisfaction with teaching than the conventional teaching group [160 (97.6%) and 150 (92.0%), P<0.05]. Conclusions:The "simulated Chinese medicine nursing clinic" teaching program effectively enhances the thinking of syndrome differientiation and related abilities for nursing, improves the learning effect of traditional Chinese medicine nursing theories and skills, and increases the learning interest in traditional Chinese medicine nursing among nursing students.

Objective To investigate the effects of calcitriol intervention on PI3K/AKT signaling pathway and wound healing in rats with diabetic foot ulcer(DFU).Methods Thirty-two male SD rats were divided into normal control(Con)group,DFU group,calcitriol low dose(L)group and calcitriol high dose(H)group.A circular wound of 5 mm in diameter and deep to the fascia was made on the dorsum of the left foot of rats in each group.HE staining was used to evaluate the histopathological changes of the wounds.Immunohistochemical method was selected to compare the distribution of CD34-positive cells and the expression of p-PI3K and p-AKT in traumatic tissues of each group.ELISA was adopted in the detection of serum IL-6,IFN-γ,TNF-α and IL-7.RT-PCR was used to detect the mRNA expression of PI3K and AKT in each group,and western blot was used to detect the protein expression of PI3K,p-PI3K,AKT,p-AKT and VEGF.Results Compared with Con group,the expressions of IL-6,IFN-γ,TNF-α,IL-7,CD34,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K,p-AKT/AKT increased,while PI3K protein expression decreased in DFU,L and H groups(P<0.05),VEGF and AKT protein expression decreased in DFV and L groups(P<0.05).Compared with DFU group,the expressions of VEGF,AKT and PI3K protein increased(P<0.05),while the expressions of p-PI3K/PI3K,p-AKT/AKT decreased in L and H groups(P<0.05),IL-6 decreased in L group(P<0.05),and CD34 expression increased in H group(P<0.05),while IL-6,IFN-γ,TNF-α and IL-7,PI3K mRNA,AKT mRNA,p-AKT protein and p-PI3K protein expression decreased(P<0.05).Compared with L group,the expressions of CD34,VEGF,AKT and PI3K protein increased(P<0.05),while IL-6,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K and p-AKT/AKT decreased in H group(P<0.05).Conclusions Calcitriol intervention may reduce the activity of the PI3K/AKT signaling pathway,inhibit inflammation,promote neovascularization,and facilitate wound healing in rats with DFU.

Objective:To develop a risk prediction model of acute cerebral infarction (ACI) in patients with type 2 diabetes mellitus (T2DM).Methods:It was a cross-sectional study. The clinical data of 798 patients with T2DM hospitalized in the Department of Endocrinology and Neurology of Shanxi Bethune Hospital from August 2021 to October 2023 were collected. Based on whether they had concurrent ACI, the patients were divided into T2DM with ACI group (case group) and pure T2DM group (control group). The patients were then allocated to a training set ( n=558) and a validation set ( n=240) in a 7∶3 ratio by the sample functions in R software. LASSO regression was employed to screen and optimize variables, and a multivariate logistic regression analysis was used to establish the nomogram prediction model. The discriminative ability, calibration, and clinical usefulness of the risk prediction model were assessed with receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis, respectively. Results:LASSO regression identified gender, age, systolic blood pressure, fasting plasma glucose (FPG), albumin (ALB), and carotid vascular condition as the variables for prediction. The multivariable logistic regression analysis showed that female ( OR=0.489, 95% CI: 0.308-0.778) and ALB ( OR=0.846, 95% CI: 0.795-0.901) were protective factors for ACI occurrence in T2DM patients, while age ( OR=1.051, 95% CI:1.025-1.077), systolic blood pressure ( OR=1.047, 95% CI: 1.034-1.059), FPG ( OR=1.185, 95% CI: 1.089-1.288), and carotid plaque ( OR=7.359, 95% CI: 3.050-17.756) were risk factors. The area under the ROC curve (AUC) for risk of ACI in the training set was 0.863(95% CI: 0.833-0.893), and it was 0.846(95% CI: 0.797-0.896) for the validation set. Calibration curves and the Hosmer-Lemeshow goodness-of-fit test indicated good model fit (training set χ2=8.311, P=0.404; validation set χ2=3.957, P=0.861). Decision curve analysis showed that the clinical effectiveness of the model was higher when the threshold probabilities of the training set and the validation set was 0.02-0.93 and 0.12-0.99, respectively. Conclusion:In this study, a prediction model of ACI risk in T2DM patients was successfully established.

Objective:To observe any effect supplementing treadmill training with external application of relaxation cream on skeletal muscle cell apoptosis and IGF-1/PI3K/Akt signaling.Methods:Eight Wistar rats formed a healthy control group (the healthy group) and muscle atrophy was induced in the left hind limbs of another 32. Those 32 rats were randomly divided into a model control group (model group), a treadmill training group (treadmill group), a relaxation cream group (TCM group), and a group which received both treadmill training and the relaxation cream (combined group). After 6 weeks of the intervention, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) was used to detect any apoptosis of skeletal muscle cells. Western blotting was employed to detect the protein expression levels of insulin-like growth factor 1 (IGF-1), phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), B-cell lymphomato-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in the skeletal muscles.Results:The number of apoptotic cells in the skeletal muscles of the treadmill, TCM and combined groups was significantly less, on average, then in the model group. The difference in the combined group was significantly greater than in the other two groups. The expression of Bcl-2 protein in the model group was significantly lower than in the healthy group, while that of Bax protein had increased significantly. Compared with the model group, a significant increase in Bcl-2 protein expression and a significant decrease in Bax protein expression were observed in both the TCM and combined groups. Compared with the model group, the expression of IGF-1, p-PI3K and p-Akt proteins had increased significantly in both the TCM and combined groups, with significantly greater increases in the combined group, on average.Conclusion:Combining treadmill training with relaxation cream can inhibit the apoptosis of skeletal muscle cells, at least in DMA rats. The mechanism may be related to activation of the IGF-1/PI3K/Akt signaling pathway, up-regulation of Bcl-2 and down-regulation of Bax.

Objective:To explore with healthy adults any effect on postural control of transcranial direct current stimulation (tDCS) applied over the left dorsolateral prefrontal cortex (L-DLPFC) and the primary motor cortex (M1).Methods:Eighteen healthy adults received 3 tDCS stimulation protocols sequentially applied to either the left dorsolateral prefrontal cortex alone, the left dorsolateral prefrontal cortex and the bilateral primary motor cortex simultaneously or sham stimulation, respectively. Each intervention protocol lasted for 20 minutes with a total current intensity of less than 4mA, with a 7-day interval between the each stimulation protocol. Single-task and dual-task walking and balance tests were administered before and after each stimulation protocol, followed by statistical analysis.Results:The results of the single-task gait function testing showed that the change in step width before and after single-target tDCS stimulation was (-0.511±1.072)cm, significantly better than with sham stimulation. In the dual-task gait function tests the change in step width after single-target tDCS stimulation was (-0.511±1.072)cm, significantly better than in the other two groups.Conclusions:Stimulating only the dorsolateral prefrontal cortex can effectively regulate cognitive-motor postural control. Multi-target tDCS offers no particular advantage.