Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

Objective:To establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.

Simultaneous management of intestinal mucosal barrier dysfunction and gut microbiota dysregulation represents a significant challenge in the treatment of inflammatory bowel disease (IBD). Herein, we report a novel system that integrates multi-enzyme mimicking cerium single-atom nanocatalysts (CeSACs) with Lactobacillus reuteri probiotics (LR@CeSACs) for multipronged management of IBD. In this system, CeSACs demonstrate robust multi-enzyme activities across a broad pH range, effectively scavenging elevated reactive oxygen species, downregulating pro-inflammatory cytokines, and suppressing the expression of fibrosis-related genes. Moreover, probiotics promote the targeting and retention of the CeSACs for sustained catalytic antioxidant therapy. In turn, the inflammation relief enabled by CeSACs promotes bacterial viability, allowing for the rapid reshaping of intestinal barrier function and the restoration of gut microbiota. Therefore, LR@CeSACs exhibit excellent catalytic anti-inflammatory and anti-fibrotic therapeutic effects, as well as a certain prophylactic effect, as demonstrated in several murine models.

Objective To investigate the predictive value of multimodal ultrasound parameters combined with systemic inflammation response index(SIRI)and neutrophil-to-lymphocyte ratio(NLR)for efficacy of neoadjuvant chemotherapy(NAC)in patients with breast cancer(BC).Methods A total of 132 BC patients in the Provincial Hospital Affiliated to Shandong First Medical University from March 2022 to March 2024 were selected as the study subjects,and they were divided into effective group(n=100)and ineffective group(n=32)according to the NAC results.Multimo-dal ultrasound parameters,SIRI,and NLR before NAC treatment were compared between the two groups.Multivariate Logistic regression analysis was used to explore the influencing factors of ineffective NAC in BC patients.Results After NAC treatment,among 132 BC patients,23 cases achieved complete remission,77 cases achieved partial remission,29 cases had stable disease,and 3 cases had disease progression.The elasticity score and resistance index(RI)in the effective group were significantly lower than those in the ineffective group,while the peak intensity(PI),area under the curve(AUC),and peak systolic velocity(PSV)were significantly higher than those in the ineffec-tive group(P＜0.05).The neutrophil count and monocyte count in the ineffective group were sig-nificantly higher than those in the effective group,while the lymphocyte count was significantly lower than that in the effectivegroup(P＜0.05).Before NAC treatment,the SIRI and NLR in the inef-fective group were significantly higher than those in the effective group(P＜0.05).The proportions of patients with non-triple-negative breast cancer and lymph node metastasis in the ineffective group were significantly higher than those in the effective group(P＜0.05).Multivariate Logistic regres-sion analysis showed that high RI,high SIRI,high NLR,high elasticity score,low PSV,low PI,low AUC,non-triple-negative breast cancer,and lymph node metastasis were risk factors for ineffec-tive NAC in BC patients(P＜0.05).Receiver operating characteristic(ROC)curve analysis showed that the AUC for predicting the efficacy of NAC in BC by the combination of multimodalultra-sound parameters,SIRI,and NLR was 0.929,which was significantly higher than that of the three independent predictors alone(P＜0.05).Conclusion The combination of multimodal ultrasound parameters,SIRI,and NLR has a high predictive value for the efficacy of NAC in BC and may serve as effective predictors for the efficacy of NAC.

OBJECTIVE To investigate the current status of air quality in clean operating rooms in Xi'an and explore the possible influencing factors,thus to provide data support for improving the quality of operating room manage-ment.METHODS According to GB50333-2013"Architectural technical code for hospital clean operating depart-ment",on-site monitoring was conducted from 2017 to 2021 on the air quality of 242 clean operating rooms in 41 hospitals in Xi'an,and the results were compared and analyzed.RESULTS Among the operating rooms being sur-veyed,130 were from secondary hospitals,112 from tertiary hospitals;seventy-nine were ClassⅠoperating rooms,26 were ClassⅡ,137 were ClassⅢ.The pass rate for settling bacterial was 98.35%,with 94.94%for ClassⅠoperating rooms,which was significantly lower than that in ClassⅡand ClassⅢ operating rooms(χ2=6.565,P=0.022).The pass rate for dust particles was 69.01%,with 43.04%for ClassⅠoperating rooms,and there was significant difference among different levels of operating rooms(χ2=37.304,P<0.001).The pass rate for dust particles in tertiary hospitals was 61.61%,lower than that in secondary hospitals(75.38%;χ2=5.340,P=0.021).The pass rate for dust particles≥0.5μm and≥5μm were 85.12%and 74.79%,respectively.Among the operating rooms with unqualified dust particles,those with both≥0.5 μm and≥5 μm dust particles not meeting standards accounted for 29.33%,and those with only≥0.5 μm dust particles not meeting standards accounted for 18.67%.Multivariate logistic regression analysis showed that influencing factors for air quality in clean operating rooms included the year of monitoring and the level of the operating room,while the sampling area and hospital level were not statistically associated with the outcomes.CONCLUSION The overall air quality of op-erating rooms in Xi'an is not optimistic,the pass rate is affected by the year of monitoring and the clean levels of the operating rooms,indicating a need to strengthen routine management and monitoring of clean operating rooms.

OBJECTIVE To investigate the current status of air quality in clean operating rooms in Xi'an and explore the possible influencing factors,thus to provide data support for improving the quality of operating room manage-ment.METHODS According to GB50333-2013"Architectural technical code for hospital clean operating depart-ment",on-site monitoring was conducted from 2017 to 2021 on the air quality of 242 clean operating rooms in 41 hospitals in Xi'an,and the results were compared and analyzed.RESULTS Among the operating rooms being sur-veyed,130 were from secondary hospitals,112 from tertiary hospitals;seventy-nine were ClassⅠoperating rooms,26 were ClassⅡ,137 were ClassⅢ.The pass rate for settling bacterial was 98.35%,with 94.94%for ClassⅠoperating rooms,which was significantly lower than that in ClassⅡand ClassⅢ operating rooms(χ2=6.565,P=0.022).The pass rate for dust particles was 69.01%,with 43.04%for ClassⅠoperating rooms,and there was significant difference among different levels of operating rooms(χ2=37.304,P<0.001).The pass rate for dust particles in tertiary hospitals was 61.61%,lower than that in secondary hospitals(75.38%;χ2=5.340,P=0.021).The pass rate for dust particles≥0.5μm and≥5μm were 85.12%and 74.79%,respectively.Among the operating rooms with unqualified dust particles,those with both≥0.5 μm and≥5 μm dust particles not meeting standards accounted for 29.33%,and those with only≥0.5 μm dust particles not meeting standards accounted for 18.67%.Multivariate logistic regression analysis showed that influencing factors for air quality in clean operating rooms included the year of monitoring and the level of the operating room,while the sampling area and hospital level were not statistically associated with the outcomes.CONCLUSION The overall air quality of op-erating rooms in Xi'an is not optimistic,the pass rate is affected by the year of monitoring and the clean levels of the operating rooms,indicating a need to strengthen routine management and monitoring of clean operating rooms.

Objective:To establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.

Objective:To investigate the risk factors for retrograde type A dissection (RTAD) associated with thoracic endovascular aortic repair (TEVAR) which provided the basis for clinical risk stratification and treatment decision.Methods:The clinical data of 1 688 patients with thoracic aortic disease who underwent TEVAR in our center from January 2004 to December 2019 were retrospectively analyzed. The pathological classification included aortic dissection (1 592 cases) and other thoracic aortic diseases (96 cases). Univariate analysis and categorical multiple logistic regression analysis were used to explore the risk factors for the development of RTAD during or after TEVAR.Results:A total of 18 cases of RTAD were found, with an overall incidence of 1.1% (18/1 688), all of which occurred in aortic dissection group. After adjusting for confounding factors, multivariate logistic regression analysis showed that the incidence of RTAD was significantly decreased(OR=0.27,95%CI 0.07-0.96, P=0.043) when the oversize of stentgraft was 11%-20%, the oversize of stentgraft was ≤10% as the control group, and the difference was statistically significant( P<0.05). The ascending aorta diameter was <40 mm as the control group, and there was no significant difference in the incidence of RTAD between the ≥40 mm group and the control group(OR=2.71,95%CI 0.94-7.84, P=0.065). Conclusions:Aortic dissection is more likely to develop RTAD than other thoracic aortic diseases. A proper stentgraft oversizing ratio could reduce the probability of RTAD. That is to say that a too low stentgraft oversizing ratio is not recommended.

Objective To investigate the effect of pathologically elevated-cyclic stretch induced by hypertension on mitochondrial biogenesis of vascular smooth muscle cells (VSMCs), and the role of PGC1α in this process. Methods The Flexcell-5000T stretch loading system in vitro was applied to VSMCs with a frequency of 1. 25 Hz and an amplitude of 5% or 15% to simulate the mechanical environment under normal physiological or hypertensive pathological conditions respectively. Western blotting and qPCR were used to detect the expression of PGC1α, citrate synthase and mitochondrial DNA (mtDNA) copy number in VSMCs under normal physiological or hypertensive pathological conditions. VSMCs were treated with PGC1α specific activator ZLN005 to promote PGC1α expression or specific interfering fragment siRNA to inhibit PGC1α expression in order to detect the effect on citrate synthase and mtDNA copy number. Results Compared with 5% physiological cyclic stretch, 15% pathologically elevated-cyclic stretch significantly suppressed the expression of PGC1α, citrate synthase and mtDNA copy number in VSMCs. Compared with control group, the protein expression of PGC1α was significantly decreased and increased respectively. When VSMCs transfected with PGC1α siRNA or incubated PGC1α activator ZLN005, the expression of citrate synthase and mtDNA copy number were also significantly down regulated and up-regulated in VSMCs accordingly. Under physiological cyclic stretch conditions, the protein level of PGC1α was significantly down-regulated by PGC1α siRNA, which also significantly down-regulated citrate synthase expression and mtDNA copy number. The protein expression of PGC1α was significantly up-regulated by ZLN005, which also enhanced the expression of citrate synthase and mtDNA copy number. Conclusions The pathological cyclic stretch induced by hypertension significantly down-regulated the expression of citrate synthase and mtDNA copy number via suppressing the expression of PGC1α, resulting in mitochondrial dysfunction of VSMCs. PGC1α may be a potential therapeutic target molecule to alleviate the progression of hypertension.

Bone regeneration remains a great clinical challenge. Low intensity near-infrared (NIR) light showed strong potential to promote tissue regeneration, offering a promising strategy for bone defect regeneration. However, the effect and underlying mechanism of NIR on bone regeneration remain unclear. We demonstrated that bone regeneration in the rat skull defect model was significantly accelerated with low-intensity NIR stimulation. In vitro studies showed that NIR stimulation could promote the osteoblast differentiation in bone mesenchymal stem cells (BMSCs) and MC3T3-E1 cells, which was associated with increased ubiquitination of the core circadian clock protein Cryptochrome 1 (CRY1) in the nucleus. We found that the reduction of CRY1 induced by NIR light activated the bone morphogenetic protein (BMP) signaling pathways, promoting SMAD1/5/9 phosphorylation and increasing the expression levels of Runx2 and Osterix. NIR light treatment may act through sodium voltage-gated channel Scn4a, which may be a potential responder of NIR light to accelerate bone regeneration. Together, these findings suggest that low-intensity NIR light may promote in situ bone regeneration in a CRY1-dependent manner, providing a novel, efficient and non-invasive strategy to promote bone regeneration for clinical bone defects.
Animals ; Rats ; Bone Morphogenetic Protein 2/metabolism* ; Bone Regeneration ; Cell Differentiation ; Circadian Clocks ; Cryptochromes/metabolism* ; Osteoblasts/metabolism* ; Osteogenesis ; Transcription Factors/metabolism*