1.Calcitriol reverses sepsis-induced immunosuppression via VDR/Ca2+/pyroptosis signaling pathway
Shenglan SHANG ; Shuo ZOU ; Yuqi WEI ; Mengchen YU ; Fan ZHOU ; Yan ZHAO ; Airong YU
China Pharmacy 2025;36(18):2232-2237
OBJECTIVE To investigate the effects of calcitriol on sepsis-induced immunosuppression and its potential mechanism. METHODS A sepsis-induced immunosuppression mice model was established using cecal ligation and puncture (CLP). The 7-day survival rate, serum levels of tumor necrosis factor- α (TNF- α), interleukin-6 (IL-6), and IL-1β were determined in sham operation group, CLP group and calcitriol group (1 μg/kg); the morphological changes of lung tissue in mice were observed. Lipopolysaccharide (LPS) tolerance macrophage models (representing sepsis-induced immunosuppression) were established using mice macrophage cell line RAW264.7 cells. The levels of TNF-α and IL-6 in cell supernatants as well as mRNA expressions of IL-1β, nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), IL-18 and caspase-1 were assessed in culture medium group, LPS group, LPS tolerance group, and calcitriol (5 μmol/L) group. The following parameters were measured: propidium iodide (PI)-positive cell ratio, caspase-1 activity, lactate dehydrogenase (LDH) release, and Ca2+ levels. RESULTS Compared with CLP group, 7-day survival rate and serum levels of TNF-α, IL-6 and IL-1β were increased significantly in calcitriol group (P<0.05). Additionally, pulmonary tissue damage was markedly attenuated in calcitriol group. Compared with LPS tolerance group, the levels of TNF-α and IL-6 in cell supernatants, mRNA expressions of IL- 1β, NLRP3, IL-18 and caspase-1, PI-positive cell ratio, caspase-1 activity, LDH release, and Ca2+ levels were all increased significantly in calcitriol group (P<0.05). CONCLUSIONS Calcitriol can reverse sepsis-induced immunosuppression, and the mechanism of action may be E-mail:yarfwy@163.com achieved by the binding of calcitriol to vitamin D receptor,which promotes the release of Ca2+ from the endoplasmic reticulum, thereby driving the NLRP3/caspase-1-mediated pyroptosis pathway.
2.RXRα modulates hepatic stellate cell activation and liver fibrosis by targeting CaMKKβ-AMPKα axis.
Lijun CAI ; Meimei YIN ; Shuangzhou PENG ; Fen LIN ; Liangliang LAI ; Xindao ZHANG ; Lei XIE ; Chuanying WANG ; Huiying ZHOU ; Yunfeng ZHAN ; Gulimiran ALITONGBIEKE ; Baohuan LIAN ; Zhibin SU ; Tenghui LIU ; Yuqi ZHOU ; Zongxi LI ; Xiaohui CHEN ; Qi ZHAO ; Ting DENG ; Lulu CHEN ; Jingwei SU ; Luoyan SHENG ; Ying SU ; Ling-Juan ZHANG ; Fu-Quan JIANG ; Xiao-Kun ZHANG
Acta Pharmaceutica Sinica B 2025;15(7):3611-3631
Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl4 and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.
3.A thermo-sensitive hydrogel targeting macrophage reprogramming for sustained osteoarthritis pain relief.
Yue LIU ; Kai ZHOU ; Xinlong HE ; Kun SHI ; Danrong HU ; Chenli YANG ; Jinrong PENG ; Yuqi HE ; Guoyan ZHAO ; Yi KANG ; Yujun ZHANG ; Yue'e DAI ; Min ZENG ; Feier XIAN ; Wensheng ZHANG ; Zhiyong QIAN
Acta Pharmaceutica Sinica B 2025;15(11):6034-6051
Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.
4.Risk factor analysis for postoperative pulmonary infections with multidrug-resistant bacteria in patients with oral squamous cell carcinoma undergoing flap repair surgery
WANG Qian ; PENG Hui ; ZHANG Liyu ; YANG Zongcheng ; WANG Yuqi ; PAN Yu ; ZHOU Yu
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(7):554-562
Objective:
To investigate the distribution patterns and risk factors for multidrug-resistant bacterial pulmonary infections in patients with oral squamous cell carcinoma (OSCC) undergoing flap reconstruction surgery, and to provide evidence for infection prevention and treatment in this population.
Methods:
This study was approved by the institutional medical ethics committee. We retrospectively analyzed sputum culture results, antimicrobial susceptibility testing data, and clinical records of 109 OSCC patients undergoing flap reconstruction. Chi-square tests were employed to identify pathogens and risk factors for multidrug-resistant bacteria (MDR) in postoperative pulmonary infections. Multivariate logistic regression analysis was conducted to determine MDR risk factors and establish a nomogram prediction model. The model’s discriminatory power, accuracy, and clinical utility were evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).
Results:
Among the 109 patients, 52 had negative sputum cultures and 57 tested positive, of whom 14 developed multidrug-resistant (MDR) pulmonary infections. Chi-square analysis revealed that blood transfusion, pre-existing pulmonary diseases, operation time ≥ 490 min, intraoperative blood loss ≥ 400 mL, and abnormal BMI were significant risk factors for postoperative MDR infections (P < 0.05). Multivariate logistic regression identified pre-existing pulmonary diseases, intraoperative blood loss ≥ 400 mL, abnormal BMI, and operative duration ≥ 490 min as independent risk factors for MDR infections (P < 0.05). The nomogram prediction model for MDR infections demonstrated an area under the ROC curve (AUC) of 0.874 (95% CI: 0.775-0.973). The calibration plot showed good agreement between predicted and observed outcomes. DCA indicated a net clinical benefit when the threshold probability for high-risk MDR infections ranged from 0.000 to 0.810. Common MDR pathogens included MDR Pseudomonas aeruginosa, MDR Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii (CRAB), and methicillin-resistant Staphylococcus aureus (MRSA).
Conclusion
Among OSCC patients undergoing flap reconstruction, MDR pulmonary infections were predominantly caused by gram-negative bacteria (including CRAB, MDR Pseudomonas aeruginosa, and MDR Klebsiella pneumoniae along with the gram-positive pathogen MRSA. Pre-existing pulmonary comorbidities, prolonged surgery duration (≥ 490 min), significant intraoperative blood loss (≥ 400 mL), and abnormal BMI were confirmed as independent risk factors for these MDR infections. The nomogram predictive model incorporating these four variables demonstrated clinically reliable accuracy in risk stratification for postoperative MDR pulmonary infections in this patient population.
5.Evaluation of the reliability and validity of the Chinese listening self-efficacy questionnaire
Wenling JIANG ; Junyan ZHU ; Qian ZHOU ; Yuqi JIN ; Yan REN ; Haifeng LI ; Zhi-wu HUANG
Journal of Audiology and Speech Pathology 2025;33(2):134-139
Objective To develop and translate the Chinese listening self-efficacy questionnaire(C-LSEQ)and to test its reliability and validity.Methods A total of 172 subjects aged≥60 years with age-related hearing loss completed the C-LSEQ questionnaire via direct interviews.Pure tone hearing threshold test,Mandarin hearing in noise test,and the hearing handicap inventory for elderly-screening(HHIE-S)were evaluated.Twenty subjects were randomly selected from the original group to complete the C-LSEQ questionnaire in 2 weeks after the initial evaluation.Results ① Reliability:The Cronbach's a coefficients of the three sub-dimensions and the overall ques-tionnaire were all>0.8,and the test-retest reliability coefficients of the three sub-dimensions and the overall ques-tionnaire were all>0.9(P<0.001).② Validity:The experts collectively evaluated the representativeness of the statements with good content validity.The convergent validity test showed that the composite reliability(CR)of the 2 sub-dimensions and the overall questionnaire were all>0.7,and the average variance extracted(AVE)were all>0.5.The CR value of the complex listening dimension was 0.655,and the AVE value was 0.937.The criterion validity test showed that the overall questionnaire and the three sub-dimensions of the C-LSEQ were significantly correlated with the pure-tone average,speech recognition thresholds in noise,and HHIE-S(P<0.001).Conclusion The C-LSEQ exhibits stable structure,with good reliability and validity.It can be used to assess listen-ing self-efficacy in adults with hearing loss,especially in the elderly with age-related hearing loss.
6.Correlation of fetal rectal ampulla abdominal diameter with gestational age and establishment of reference values in low-risk fetuses at 18~40 weeks of pregnancy
Yuqi ZHANG ; Kesong ZHOU ; Shiquan ZHANG ; Lei TANG ; Enxiu XIE ; Hongquan LIAO ; Tao YANG
The Journal of Practical Medicine 2025;41(6):882-888
Objective To examine the correlation between fetal rectal ampulla diameter and gestational age,and to establish reference value ranges for low-risk fetuses between 18 and 40 weeks of gestation in Yibin region.Methods A total of 1,103 low-risk singleton pregnant women between 18 and 40 weeks of gestation were recruited from five hospitals in Yibin City(the Second People's Hospital,the First People's Hospital,the Fifth People's Hospital,the Maternal and Child Health Hospital of Yibin City,and the Maternal and Child Health Hospital of Cuiping District)for routine level Ⅰ,Ⅱ,and Ⅲ prenatal ultrasound screening from October 2022 to March 2024.Fetal rectal ampulla diameters,including anteroposterior diameter,transverse diameter,and area,were measured using prenatal ultrasound.The normality of these measurements was assessed using the Shapiro-Wilk test.Scatter plots depicting the relationship between fetal rectal ampulla diameter parameters and gestational age were generated using the"Overlap Scatter Plot"function in SPSS.Percentiles were calculated using the"Explore"function in SPSS,with reference value ranges described by P5,P10,P50,P90,and P95.Results The visual-ization rate of the fetal rectal ampulla diameter was 55%at 18~20 weeks of gestation,100%at 21~37 weeks,and 96%at greater than 37 weeks.The fetal rectal ampulla diameter exhibited a significant positive correlation with gestational age(r=0.925~0.949,P<0.01).Conclusions Prenatal ultrasound measurement of fetal rectal ampulla diameter demonstrates a robust correlation with gestational age.The reference intervals for the rectal ampulla diameter of low-risk fetuses between 18 and 40 weeks of gestation,established in this study,may offer valuable theoretical guidance for prenatal diagnosis of fetal rectal and anal abnormalities in Yibin region.
7.Progress on mechanism of IL-32 in transformation process of gastric"inflammation to cancer"
Weijian ZHANG ; Yuqi WU ; Dishu ZHOU ; Shuya SONG ; Xinxin HONG ; Yifei XU ; Tiantian CAI ; Shaoju GUO ; Huafeng PAN ; Haiwen LI
Chinese Journal of Immunology 2025;41(9):2264-2271
IL-32 is a multifunctional cytokine with both pro-inflammatory and anti-inflammatory properties.It has been proved that expression of IL-32 increases with progression of gastric mucosal diseases and severity of gastric cancer(GC),thus participating in process of gastric"inflammation-cancer"transformation.However,how IL-32 affects malignant transformation of gastric"inflamma-tion-cancer"and finally leads to adverse outcome of GC invasion and migration is still controversial.In order to better clarify regulatory effect and possible mechanism of abnormal expression of IL-32 on different histopathological stages of gastric"inflammation-cancer"transformation,and to explore new directions and breakthroughs in molecular mechanism of early truncation and treatment of gastric precancerous lesion(GPL),we searched literatures related to IL-32 in six authoritative databases at home and abroad,such as Pubmed,Web of Science and CNKI,in past 30 years.It was found that pathogenicity or protective function of IL-32 in different histo-pathological stages of gastric"inflammation-cancer"transformation depended on its different subtypes,secretory forms,surrounding cytokine environment,disease status and genetic factors.IL-32 may regulate polarization of macrophages through NF-κB,MAPK,COX2,PR3,IDO,NOD,PKCδ,FAK and STAT3,amplify or inhibit chronic inflammatory stimulation of gastric mucosa,and thus participate in process of gastric"inflammation-cancer"transformation.Our new understanding of role of IL-32 in different stages of Cor-rea cascade may contribute to development of cytokine-directed therapy,and therapy aimed at regulating different alternative splicing subtypes of IL-32 and targeting IL-32 signals can be used as a new strategy for medical treatment of GPL and GC in future.
8.Practical exploration on the responsibilities and operation specifications of assistants in robotic radical gastrectomy
Yulong TIAN ; Yuqi SUN ; Xiaoning KANG ; Yan WANG ; Shougen CAO ; Xiaodong LIU ; Zequn LI ; Gan LIU ; Xiaojie TAN ; Cheng MENG ; Haitao JIANG ; Zhaojian NIU ; Yanbing ZHOU
Chinese Journal of Gastrointestinal Surgery 2025;28(8):937-941
Robot-assisted surgery with its advantages such as three-dimensional high-definition vision, dexterous robotic arms, and tremor filtration, is increasingly being applied to complex radical gastrectomy. However, the role of the surgical assistant remains crucial during the procedure. The assistant is responsible for tasks outside the console, including adjusting robotic arms, changing instruments, exposing the surgical field, and addressing unexpected situations. The technical proficiency of the assistant and their collaboration efficiency with the primary surgeon directly impact the smoothness of surgery and patients' outcomes. With the expansion of robot-assisted surgical indications, the establishment of a standardized training system and the optimization of team collaboration models have become urgent challenges to address. This article draws on the author's practical experience as an assistant in robot-assisted gastric cancer surgeries, conducting an in-depth analysis of the responsibilities and operational skills of surgical assistants in robot-assisted procedures. The aim is to develop a relatively comprehensive set of operational guidelines for surgical assistants in robot-assisted radical gastrectomy, providing valuable references for enhancing the overall efficiency of surgical teams and improving surgical outcomes.
9.Practical research on the quality control system of hospital logistic maintenance service based on closed-loop theory
Yuqi ZHOU ; Jianming WANG ; Zhanqi HOU
Modern Hospital 2025;25(4):591-594
As an important support for hospital operations,hospital logistic maintenance services suffer from pain points such as low efficiency and passive maintenance.The fundamental reason is the lack of a closed-loop mechanism.Based on the closed-loop theory and combined with mathematical modeling,this paper constructs a quality control system for logistic mainte-nance services and proposes a four-stage management process:In the planning stage,optimization goals and constraints are clari-fied.In the design stage,a comprehensive optimization model is established to minimize response time deviation and total mainte-nance costs while maximizing the one-time repair rate.In the execution stage,a maintenance task allocation matrix is generated based on the model solution to optimize resource scheduling.In the inspection stage,RTD,FFR,and QMS are introduced to quantitatively evaluate service performance.In the improvement stage,problem feedback is addressed,and model parameters are adjusted to form a closed loop.Hospital A is used as a practical case study,and the application effect of the quality control sys-tem is verified through analysis of its maintenance data.The quality control system has significant effects on optimizing the re-sponse efficiency,stability,and resource utilization of logistic maintenance services,providing a practical reference for other medical institutions.
10.Sero-epidemiological investigation and analysis of akabane disease and bluetongue of cattle of Guizhou Province
Tingting XU ; Hao WANG ; Qiuyu WU ; Xingwei NI ; Yuqi ZUO ; Jiafu SHANG ; Yanyan LIU ; Xuehui ZHOU ; Xiaowei YANG ; Guangwei ZHAO ; Xia LIU
Chinese Journal of Veterinary Science 2025;45(9):1895-1901
To investigate the infection status of two arboviruses,akabane orthobunyavirus(AKAV)and bluetongue virus(BTV),in cattle herds of Guizhou Province,we employed the indirect ELISA method to detect AKAV and BTV antibody levels in the present experiment.A total of 1504 bovine serum samples from 37 large-scale farms and 88 free-range households from 26 districts or coun-ties of 7 cities(prefectures)of Guizhou Province were collected to detect AKAV antibody levels.Additionally,1 241 serum samples from 30 large-scale farms and 15 free-range households in 19 districts or counties of 3 cities(prefectures)were tested for BTV antibody levels.Moreover,two influencing factors,breeding mode and sampling season,were statistically analyzed for their effects.The results showed that the overall positive rate of AKAV antibodies was 11.64%(175/1 504),with individual positive rates of 13.20%(123/934)and 9.12%(52/570)in large-scale farms and free-range households,respectively.No significant differences were observed between the two groups.However,the farm positive rate(64.86%,24/37)in large-scale farms was significantly higher than that(26.14%,23/88)in free-range households.Seasonal statistics showed that the positive rate was highest during the summer season at 60.00%(12/20).The total positive rate of BTV antibodies was 25.42%(222/1 241).The farm positive rate and individual positive rate in free-range households were 66.67%(10/15)and 41.91%(57/136),respectively.For large-scale farms,these rates were 60.00%(18/30)and 14.93%(165/1 105),respectively.The individual pos-itive rate in free-range households was significantly higher than that in large-scale farms.Seasonal statistics showed that the positive rates in summer and autumn seasons were 50.00%(5/10)and 72.41%(21/29),respectively,both of which were significantly higher than those in winter and spring seasons.All these findings indicated that both AKAV and BTV were present to a certain ex-tent in Guizhou Province,with seasonality.Furthermore,differences were observed between the different breeding modes.Our results could provide a data reference for the formulation of preven-tion and control measures for the two insect-borne diseases.


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