ObjectiveTo assess the efficacy and safety of the Qi-regulating and phlegm-removing method（Liu Junzitang Combined with Linggang Wuwei Jiangxintang） for treating acute exacerbations of chronic obstructive pulmonary disease （AECOPD） with increased eosinophils （EOS）. MethodsSixty-eight AECOPD patients with increased EOS who were hospitalized in the Department of Pulmonary Diseases of Jinhua Traditional Chinese Medicine Hospital from April 2023 to April 2024 were recruited and randomly assigned to an experimental group （EG） or a control group （CG）. Both groups received conventional Western medicine， with the EG additionally receiving Liujunzitang and Linggan Wuwei Jiangxintang. The therapeutic efficacy indicators were measured after the treatment. The main therapeutic efficacy indicators included partial pressure of oxygen （PaO₂） and partial pressure of carbon dioxide （PaCO₂）. The secondary efficacy indicators included the TCM symptom scores， the COPD Assessment Test （CAT） score， the Modified Medical Research Council （mMRC） Dyspnea Scale score， and the length of hospital stay. The indicators were measured at baseline and on days 3 and 7 of intervention. The safety was evaluated based on the adverse events. ResultsBaseline characteristics were not statistically different between the two groups. Compared with CG， EG showed no significant difference in PaO₂ （P=0.773）， PaCO₂ （P=0.632） and or CAT score （P=0.336） at on day 3 but better PaO₂ （P=0.004）， PaCO₂ （P=0.008）， and CAT score （P=0.013） were significantly better at on day 7. Compared with CGAfter treatment， EG had lower TCM syndrome scores of than CG EG on day 3 （P=0.005） and day 7 were significantly decreased （P0.001）. There was no significant difference in mMRC score between the two groups on day 3 （P=0.514） and day 7 （P=0.176） as wasor the length of hospital stay （P=0.915）. The generalized linear mixed model （GLMM） showed that compared with CG， EG had significant improvements over time in PaO₂， PaCO₂， TCM syndrome symptom scores， CAT score， and mMRC score. ConclusionRegulating qi Qi and removing phlegm combined with conventional Western medicine can significantly alleviateimprove the clinical symptoms and improve the lung function of AECOPD patients with increased EOS increased AECOPDwhich has and demonstrates good safety.

ObjectiveTo assess the efficacy and safety of the Qi-regulating and phlegm-removing method（Liu Junzitang Combined with Linggang Wuwei Jiangxintang） for treating acute exacerbations of chronic obstructive pulmonary disease （AECOPD） with increased eosinophils （EOS）. MethodsSixty-eight AECOPD patients with increased EOS who were hospitalized in the Department of Pulmonary Diseases of Jinhua Traditional Chinese Medicine Hospital from April 2023 to April 2024 were recruited and randomly assigned to an experimental group （EG） or a control group （CG）. Both groups received conventional Western medicine， with the EG additionally receiving Liujunzitang and Linggan Wuwei Jiangxintang. The therapeutic efficacy indicators were measured after the treatment. The main therapeutic efficacy indicators included partial pressure of oxygen （PaO₂） and partial pressure of carbon dioxide （PaCO₂）. The secondary efficacy indicators included the TCM symptom scores， the COPD Assessment Test （CAT） score， the Modified Medical Research Council （mMRC） Dyspnea Scale score， and the length of hospital stay. The indicators were measured at baseline and on days 3 and 7 of intervention. The safety was evaluated based on the adverse events. ResultsBaseline characteristics were not statistically different between the two groups. Compared with CG， EG showed no significant difference in PaO₂ （P=0.773）， PaCO₂ （P=0.632） and or CAT score （P=0.336） at on day 3 but better PaO₂ （P=0.004）， PaCO₂ （P=0.008）， and CAT score （P=0.013） were significantly better at on day 7. Compared with CGAfter treatment， EG had lower TCM syndrome scores of than CG EG on day 3 （P=0.005） and day 7 were significantly decreased （P0.001）. There was no significant difference in mMRC score between the two groups on day 3 （P=0.514） and day 7 （P=0.176） as wasor the length of hospital stay （P=0.915）. The generalized linear mixed model （GLMM） showed that compared with CG， EG had significant improvements over time in PaO₂， PaCO₂， TCM syndrome symptom scores， CAT score， and mMRC score. ConclusionRegulating qi Qi and removing phlegm combined with conventional Western medicine can significantly alleviateimprove the clinical symptoms and improve the lung function of AECOPD patients with increased EOS increased AECOPDwhich has and demonstrates good safety.

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.

The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.
Animals ; Caenorhabditis elegans/genetics* ; Endosomes/immunology* ; Caenorhabditis elegans Proteins/immunology* ; Phosphatidylinositol 4,5-Diphosphate/immunology* ; Immunity, Innate ; Pseudomonas aeruginosa/immunology* ; rab GTP-Binding Proteins/genetics* ; Diglycerides/metabolism*

Objective:To investigate the impact of daily step count on glycemic outcomes in community residents with impaired glucose tolerance (IGT).Methods:This was a prospective cohort study, in October 2018, 204 residents who met the criteria of IGT were recruited in the Shijingshan District in Beijing. The subjects were tested for fasting blood glucose, oral glucose tolerance test 2-hour blood glucose (2hBG), glycated hemoglobin A 1c (HbA 1c), lipid profile, liver and kidney function, as well as measurements of height, weight and waist circumference. A dedicated mobile application was used to deliver prediabetes health knowledge monthly. Online guidance was provided to answer questions and daily step count was collected using the application. Three years later, a follow-up was conducted to assess the participants′ glycemic outcomes and other indexes, and a total of 142 participants completed the follow-up review. According to daily step count, the subjects were categorized into high step count group (42 cases,>7 000 steps daily), moderate step count group (54 cases, 5 000-7 000 steps daily), and low step count group (46 cases,<5 000 steps daily). Subjects were categorized into diabetes group (30 cases), prediabetes group (77 cases) and normal glucose tolerance group (35 cases) with glycemic outcomes. Independent sample t test was used to compare the differences in blood glucose, blood lipids, and step counts between the two groups. Kruskal-Wallis H test or one-way ANOVA was used to compare the differences in blood glucose, blood lipids, and step counts between multiple groups. The χ2 test was used to compare the differences in glycemic outcomes between multiple groups. Multivariate logistic regression analysis was used to assess the impact of daily step counts and body mass index on glycemic outcomes. Linear regression analysis was used to evaluate the relationship between daily step counts and 2 h BG. Results:A total of 142 participants completed the 3-year follow-up, including 43 males and 99 females, with a mean age of (60.15±5.67) years. At baseline, males had significantly higher body mass index, waist circumference, and fasting blood glucose when compared to those in females [(26.97±2.43) vs (24.89±2.93) kg/m 2, (92.68±7.75) vs (83.83±8.60) cm, (5.83±0.61) vs (5.62±0.52) mmol/L], the total cholesterol and HDL-C were also significantly lower in males than those in females [(5.10±1.16) vs (5.55±0.95) mmol/L, (1.35±0.34) vs (1.56±0.35) mmol/L] (all P<0.05). After 3-year follow-up, 21.1% (30/142) of IGT participants progressed to diabetes, with an annual conversion rate of approximately 7%. The normal glucose tolerance group showed significantly higher daily step counts when compared with the prediabetes and diabetes groups [(7 886±2 867) vs (5 981±2 655) vs (4 117±2 674) steps] ( H=31.778, P<0.001). Individuals with higher daily step counts exhibited lower body mass index, 2 h BG, and HbA 1c level when compared with those in the ones with moderate and low step counts [(24.26±3.09) vs (25.44±3.38) vs (26.26±3.59) kg/m 2, (7.50±1.71) vs (9.15±3.30) vs (11.19±3.84) mmol/L, 5.97%±0.46% vs 6.14%±0.99% vs 6.40%±0.96%] (all P<0.05). Higher step count was positively correlated with the reversal of prediabetes to normal blood glucose levels (moderate step count, OR=0.297, 95% CI: 0.109-0.804; low step count, OR=0.055, 95% CI: 0.010-0.287), lower daily step count correlated positively with prediabetes progressing to diabetes ( OR=4.857, 95% CI: 1.140-20.689) (all P<0.05). For every additional 1 000 steps per day, the 2 h BG decreased by 0.5 mmol/L. Conclusion:As daily step count increases, the glucose metabolism improves in IGT community residents. Higher daily step count is associated with reversal of IGT to normal glucose tolerance, while lower daily step count may be associated with the progression of IGT to diabetes.

Objective:To investigate the efficacy and safety of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis.Methods:A retrospective analysis was carried out on 46 patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis who received endovascular treatment at the Strategic Support Force Medical Center from January 2015 to August 2022. Twenty-seven patients underwent balloon angioplasty alone and 19 patients underwent acute stent implantation. The baseline characteristics, modified thrombolysis in cerebral infarction (mTICI) score of the responsible vessels, modified Rankin scale (mRS) score 90 days after operation, incidence of symptomatic intracranial hemorrhage and mortality of the two groups were evaluated.Results:The proportion of effective recanalization of the offending vessels (mTICI≥2b) in the acute stenting group was slightly higher than that in the balloon angioplasty group (16/19 vs. 81.5%), but the difference was not statistically significant ( P>0.05). Besides, there was no significant difference in the median of mRS between the acute stenting group [3.0(0, 4.0)] and the balloon angioplasty group [4.0(1.0, 5.0)] 90 days after operation ( P>0.05). In terms of safety, the incidence of symptomatic intracranial hemorrhage and mortality were comparable between the two groups ( P>0.05). Conclusions:The effect of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis is not inferior to that of balloon angioplasty, and it does not increase the risk of intracranial bleeding complications.

Objective To evaluate the intraoperative identification of ectopic parathyroid tissue in the central neck region using autofluorescence point-spectral analysis(AFPSA)combined with immune colloidal gold technique(ICGT),for guiding total parathyroidectomy(TPTX)or clean parathyroidectomy(CPTX)in the management of secondary hyperparathyroidism(SHPT).Methods Retrospectively collected and compared the clinical data of 64 patients with SHPT from October 2019 to June 2023.In the observation group,TPTX was performed as the initial procedure in 36 cases,followed by sampling of suspicious targets using AFPSA in the central neck area and subsequent detection through ICGT.CPTX was then conducted if a positive result was obtained.On the other hand,the control group consisted of 28 cases where only TPTX was performed without any additional tests during surgery.The surgical data,parathyroid hormone(PTH)levels,blood calcium levels,blood phosphorus levels,alkaline phosphatase(ALP)levels,regression of clinical symptoms,changes in parathyroid function and occurrence of hypocalcemia were compared between these two groups.Results In the observation group,there were 9 cases of AFPSA-ICGT positivity,including 2 left-sided cases,4 right-sided cases,and 3 thymic cases;among these posi-tive cases,there were a total of 10 locations with mildly hyperplastic or nonhyperplastic microscopic parathyroid tissue.The difference in the number of total parathyroid glands removed(including ectopic)between the two groups was statistically significant(P<0.05).At both 3 and 6 months postoperatively,ALP levels in the observation group were significantly lower than those in the control group(P<0.01 and P<0.001 respectively);at 6 months postoperatively,differences in PTH and blood phosphorus levels between the two groups were also statistically significant(P<0.05 and P<0.001 respectively).Joint bone pain and skin itching recurred in some patients within the control group at six months after surgery(P<0.05),whereas recurrence of SHPT was less frequent within the observation group compared to controls(P<0.05);however,no statistically significant differences were observed regarding postoperative hypoparathyroidism or hyperparathyroidism as well as hypocalcemia between either groups.Conclusion The AFPSA-ICGT intraoperative test can be utilized to guide surgery for SHPT,enabling accurate and efficient identification as well as safe targeting of parathyroid tissues that may not exhibit obvious hyperplasia in the central cervical region.