ObjectiveBased on the concept of quality by design（QbD）， the processing process of calcined Pyritum was optimized， and its X-ray diffraction（XRD） fingerprint was established. MethodsThe safety， effectiveness and quality controllability of calcined Pyritum were taken as the quality profile（QTPP）， the color， hardness， metallic luster， phase composition， the contents of heavy metals and hazardous elements were taken as the critical quality attributes（CQAs）， and the calcination temperature， calcination time， paving thickness and particle size were determined as the critical process parameters（CPPs）. Differential thermal analysis， X-ray diffraction（XRD） and inductively coupled plasma mass spectrometry（ICP-MS） were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum. Then， based on the criteria importance through intercriteria correlation（CRITIC）-entropy weight method， the optimal processing process of calcined Pyritum was optimized by orthogonal test. Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process， and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures， and similarity evaluation and cluster analysis were carried out. ResultsThe results of single factor experiments showed that the physical phase of Pyritum changed from FeS₂ to Fe₇S₈ during the process of temperature increase， the color gradually deepened from dark yellow， and the contents of heavy metals and harmful elements decreased. The optimized processing process of calcined Pyritum was as follows：calcination temperature at 750 ℃， calcination time of 2.5 h， paving thickness of 3 cm， particle size of 0.8-1.2 cm， vinegar quenching 1 time［Pyritum-vinegar（10∶3）］. After calcination， the internal structure of Pyritum was honeycomb-shaped， which was conducive to the dissolution of active ingredients. XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established. The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96， and it could effectively distinguish the raw products and unqualified products. ConclusionTemperature is the main factor affecting the quality of calcined Pyritum. After processing， the dissolution of the effective components in Pyritum increases， and the contents of heavy metals and harmful substances decrease， reflecting the function of processing to increase efficiency and reduce toxicity. The optimized processing process is stable and feasible， and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.

ObjectiveBased on the concept of quality by design（QbD）， the processing process of calcined Pyritum was optimized， and its X-ray diffraction（XRD） fingerprint was established. MethodsThe safety， effectiveness and quality controllability of calcined Pyritum were taken as the quality profile（QTPP）， the color， hardness， metallic luster， phase composition， the contents of heavy metals and hazardous elements were taken as the critical quality attributes（CQAs）， and the calcination temperature， calcination time， paving thickness and particle size were determined as the critical process parameters（CPPs）. Differential thermal analysis， X-ray diffraction（XRD） and inductively coupled plasma mass spectrometry（ICP-MS） were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum. Then， based on the criteria importance through intercriteria correlation（CRITIC）-entropy weight method， the optimal processing process of calcined Pyritum was optimized by orthogonal test. Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process， and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures， and similarity evaluation and cluster analysis were carried out. ResultsThe results of single factor experiments showed that the physical phase of Pyritum changed from FeS₂ to Fe₇S₈ during the process of temperature increase， the color gradually deepened from dark yellow， and the contents of heavy metals and harmful elements decreased. The optimized processing process of calcined Pyritum was as follows：calcination temperature at 750 ℃， calcination time of 2.5 h， paving thickness of 3 cm， particle size of 0.8-1.2 cm， vinegar quenching 1 time［Pyritum-vinegar（10∶3）］. After calcination， the internal structure of Pyritum was honeycomb-shaped， which was conducive to the dissolution of active ingredients. XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established. The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96， and it could effectively distinguish the raw products and unqualified products. ConclusionTemperature is the main factor affecting the quality of calcined Pyritum. After processing， the dissolution of the effective components in Pyritum increases， and the contents of heavy metals and harmful substances decrease， reflecting the function of processing to increase efficiency and reduce toxicity. The optimized processing process is stable and feasible， and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective To systematically evaluate the short-term efficacy and safety of lung subsegmentectomy and segmentectomy in the treatment of small pulmonary nodules. Methods Computer searches were conducted on PubMed, The Cochrane Library, EMbase, Scopus, Web of Science, SinoMed, Wanfang Data, VIP, and CNKI databases to collect relevant literature on the short-term efficacy and safety of lung subsegmentectomy and segmentectomy for small pulmonary nodules from the inception to April 2024. Two researchers independently screened the literature and extracted data according to inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software, and the Newcastle-Ottawa Scale (NOS) was used to assess the quality of the selected literature. Results A total of 15 retrospective cohort studies with 2417 patients were included, among whom 796 patients underwent lung subsegmentectomy and 1621patients underwent segmentectomy. The NOS scores of the included literature were all≥6 points. Meta-analysis results showed that compared with segmentectomy, lung subsegmentectomy had a lower overall postoperative complication rate [OR=0.54, 95%CI (0.39, 0.75), P<0.01] and fewer lymph nodes dissected [MD=−0.43, 95%CI (−0.81, −0.06), P=0.02]. There was no statistical difference between the two surgical methods in terms of operation time [MD=5.11, 95%CI (−4.02, 14.23), P=0.27], intraoperative blood loss [MD=−14.62, 95%CI (−29.58, 0.34), P=0.06], postoperative hospital stay [MD=−0.24, 95%CI (−0.49, 0.01), P=0.06], postoperative drainage time [MD=−0.14, 95%CI (−0.46, 0.18), P=0.40], intraoperative margin width [MD=0.10, 95%CI (−0.16, 0.35), P=0.46], or recurrence rate [OR=1.57, 95%CI (0.53, 4.61), P=0.42]. Subgroup analysis results showed that when using uniportal video-assisted thoracoscopy for surgery, compared with segmentectomy, lung subsegmentectomy had less intraoperative blood loss [MD=−15.57, 95%CI (−28.84, −2.30), P=0.02], shorter postoperative hospital stay [MD=−0.49, 95%CI (−0.63, −0.35), P<0.01], shorter postoperative drainage time [MD=−0.19, 95%CI (−0.35, −0.03), P=0.02], and lower overall complication rate [OR=0.55, 95%CI (0.31, 0.98), P=0.04]. Conclusion Lung subsegmentectomy can achieve similar efficacy as segmentectomy and has a lower overall postoperative complication rate. In terms of safety, lung subsegmentectomy can achieve a margin range close to that of segmentectomy. When performing uniportal thoracoscopic surgery, lung subsegmentectomy has advantages over segmentectomy in terms of intraoperative blood loss, postoperative hospital stay, and drainage time.

Objective:To explore the application effects of a teaching for understanding (TfU) model based on outcome-based education (OBE) in clinical nursing internship in dermatology.Methods:We assigned 34 nursing interns at the department of dermatology of a grade A tertiary hospital in Chengdu in 2021 to observation group to receive instruction using an OBE-based TfU model and another 34 nursing interns in 2022 to control group to be taught using a traditional teaching model. The two groups were compared for theoretical and practical assessment scores, core competencies, clinical communication, and satisfaction with teaching. SPSS 26.0 was used to perform the t-test and chi-square test. Results:The observation group had significantly higher scores than the control group for theoretical assessment [(90.63±2.84) vs. (85.84±4.50)] and practical assessment [(93.15±1.67) vs. (91.12±2.71)]; core competencies overall [(154.38±8.05) vs. (150.18±6.96)] and lifelong learning [(20.18±1.90) vs. (18.85±1.85)], general clinical skills [(23.06±3.30) vs. (18.85±1.85)], and critical thinking and reasoning ability [(11.68±1.47) vs. (10.62±1.41)]; and communication abilities overall [(90.94±5.36) vs. (84.50±5.79)] and harmonious relationship establishment [(20.21±1.86) vs. (18.76±1.92)], patient problem confirmation [(16.91±1.69) vs. (15.26±2.09)], keen listening [(17.35±1.32) vs. (15.44±2.06)], and effective information transmission [(8.91±1.60) vs. (7.85±1.73)] compared with the control group (all P<0.05). The score of satisfaction with teaching of the observation group was significantly higher than that of the control group [(94.12±4.99) vs. (90.53±7.38), P<0.05). Conclusions:The TfU model based on OBE can effectively improve nursing students' theoretical and practical assessment scores, core competencies, communication skills, and satisfaction with internship teaching, which is conducive to their all-round development and professional practice. In addition, this study provides innovative ideas and reform directions for clinical nursing practice teaching.

Aim To study the resistance of SIRT3 ex-pression in dopaminergic neurons against the inflamma-tory damage caused by microglia activation and its re-lated mechanism.Methods Dopaminergic neurons(MN9D cells)and microglia(BV-2 cells)were co-cultured to establish an inflammatory injury model in vitro.MN9D cells were divided into the control group,model group,SIRT3 group and SIRT3+PJ34 group.mRNA levels were analyzed by real-time quantitative polymerase chain reaction,cell apoptosis rate was de-tected by flow cytometry,changes in mitochondrial membrane potential were tested by JC-1 method,and the opening of mitochondrial permeability transport pore(mPTP)was analyzed by co-incubation of calce-in-AM and CoCl2.The protein expression was detected by Western blot.Results Compared to the model group,overexpression of SIRT3 in the SIRT3 group significantly reduced the apoptosis rate of MN9D cells.It also led to a significant increase in the expression of SIRT3 and SOD2 genes,as well as a notable decrease in PARP-1,tumor necrosis factor-α,and interleukin 1β(IL-1β)protein expressions.Moreover,it resulted in a substantial reduction in the p-NF-κB p65/NF-κB p65 ratio.There was an improvement observed in mito-chondrial membrane potential along with decreased mPTP opening and ROS production in the SIRT3 group.These differences among these groups were sta-tistically significant(all P＜0.05).After inhibiting PARP-1 activity of MN9D cells in the SIRT3+PJ34 group,except for the insignificant changes in SIRT3 and IL-1 β protein expression,the changing trend of other indicators was further enhanced on the basis of SIRT3 group.The differences between two groups re-mained statistically significant(all P＜0.05).Con-clusions SIRT3 expression can attenuate the inflam-matory damage of dopaminergic neurons induced by microglia activation,and the mechanism may be relat-ed to improving mitochondrial function,inhibiting PARP-1 activity and NF-κB signaling pathway caused by the reduction of ROS production.

Objective To explore the diagnostic value of ultrasound for thyroid nodules with a spoke-wheel blood flow pattern.Methods The clinical data of the patients with thyroid nodules presenting a spoke-wheel blood flow pattern examined by ultrasound were collected,and the gray-scale ultrasound features of the nodules were recorded.The diagnostic performance of the Thyroid Imaging Reporting and Data System by American College of Radiology(ACR TI-RADS),Chinese Thyroid Imaging Reporting and Data System(C-TIRADS),and combined specific indicators for the thyroid nodules with a spoke-wheel blood flow pattern was evaluated by comparison with the pathological results,which was regarded as the gold standard.Results A total of 64 patients with thyroid nodules were finally included,including 47 patients with malignant nodules and 17 patients with benign nodules.In addition to the general ultrasound features,central scar mostly appeared in malignant nodules(x2=5.968,P=0.015),while central coarse calcification was more common in benign nodules(x2=10.899,P=0.001).After the combination of central scar and central gross calcification,the diagnostic performance of ACR TI-RADS and C-TIRADS was improved(both P＜0.001).Conclusions When the thyroid nodule shows a spoke-wheel blood flow pattern,one should be cautious of the possibility of malignancy.Combining central scar and central coarse calcification can improve the accuracy of ultrasonic diagnosis.

Purpose: Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients. Materials and Methods: Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m2 nab-paclitaxel, 800 mg/m2 gemcitabine, and 25 mg/m2 cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy. Results: After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients’ survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1–positive (PD-1+) cells (p=0.032) were observed in the response patients. Conclusion In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.

Humans ; Child ; Retrospective Studies ; Thrombocytosis/etiology*

ObjectiveTo investigate the effect of myosin heavy chain 7 gene-derived miRNA-208b-3p on the fibrotic phenotype of cardiac fibroblasts. MethodsmiRNA chip array was performed to detect the dysregulated miRNAs in the myocardium of diabetic db/db mice and db/m control mice. Neonatal mouse ventricular cardiomyocytes （NMVCs） and cardiac fibroblasts （CFs） were isolated from C57BL/6 mice and cultured. Real-time quantitative PCR （RT-qPCR） was conducted to determine the expression of miR-208b-3p in mouse CFs and NMVCs subjected to angiotensinⅡ（AngⅡ） and high glucose plus glucose oxidase （G/Go） treatment， respectively. Cell counting kit 8（CCk8） assay， flow cytometry and determination of fibrosis-related protein， including COL1A1， COL3A1and α-SMA， were performed in mCFs transfected with miR-208b-3p. Dual luciferase reporter assay was performed to confirm the interaction between miR-208b-3p and the 3'-UTR of metal response element binding transcription factor 2 （Mtf2） and progesterone receptor membrane component 1（Pgrmc1）， respectively. The expressions of Mtf2 and Pgrmc1 at the mRNA and protein levels in mCFs after miR-208b-3p mimic transfection were determined using RT-qPCR and Western blot assay， respectively. The small interfering RNA （siRNA） was used to inhibit Mtf2 and Pgrmc1 expression in mCFs， and the effects of Mtf2 siRNA， Pgrmc1 siRNA and miR-208b-3p on fibrosis-related protein expression in mCFs were investigated. ResultsResults of miRNA chip array and RT-qPCR assay showed that miR-208b-3p was up-regulated in the myocardium of the diabetic db/db mice. miR-208b precursor and the host gene of Myh7 were consistently increased in db/db mice. miR-208b-3p and Myh7 mRNA were expressed in mCFs and NMVCs， but the levels of miR-208b-3p and Myh7 mRNA in NMVCs were much higher than those in mCFs. miR-208b-3p was up-regulated in mCFs and NMVCs subjected to Ang Ⅱ and G/Go treatment， respectively. miR-208b-3p could significantly enhance fibrosis-related protein， including COL1A1， COL3A1 and α-SMA， in mCFs， without affecting the proliferation activity and cell cycle distribution of mCFs. Dual luciferase reporter assay revealed the interactions of miR-208b-3p with the 3'-UTR of Mtf2 and Pgrmc1. The results of RT-qPCR and Western blotting confirmed that miR-208b-3p inhibited Mtf2 and Pgrmc1 expression at the post- transcriptional level. Transfection with miR-208b-3p mimic， Mtf2 siRNA and Pgrmc1 siRNA could consistently enhance the fibrosis-related protein expression in the cardiac fibroblasts. ConclusionsmiR-208b-3p enhances fibrosis-related gene expression by targeting Mtf2 and Pgrmc1in mCFs.