1.Hydrogen sulfide ameliorates hypoxic pulmonary hypertension in rats by inhibiting aerobic glycolysis-pyroptosis.
Yuan CHENG ; Yun-Na TIAN ; Man HUANG ; Jun-Peng XU ; Wen-Jie CAO ; Xu-Guang JIA ; Li-Yi YOU ; Wan-Tie WANG
Acta Physiologica Sinica 2025;77(3):465-471
The present study aimed to explore whether hydrogen sulfide (H2S) improved hypoxic pulmonary hypertension (HPH) in rats by inhibiting aerobic glycolysis-pyroptosis. Male Sprague-Dawley (SD) rats were randomly divided into normal group, normal+NaHS group, hypoxia group, and hypoxia+NaHS group, with 6 rats in each group. The control group rats were placed in a normoxic (21% O2) environment and received daily intraperitoneal injections of an equal volume of normal saline. The normal+NaHS group rats were placed in a normoxic environment and intraperitoneally injected with 14 μmol/kg NaHS daily. The hypoxia group rats were placed in a hypoxia chamber, and the oxygen controller inside the chamber maintained the oxygen concentration at 9% to 10% by controlling the N2 flow rate. An equal volume of normal saline was injected intraperitoneally every day. The hypoxia+NaHS group rats were also placed in an hypoxia chamber and intraperitoneally injected with 14 μmol/kg NaHS daily. After the completion of the four-week modeling, the mean pulmonary artery pressure (mPAP) of each group was measured using right heart catheterization technique, and the right ventricular hypertrophy index (RVHI) was weighed and calculated. HE staining was used to observe pathological changes in lung tissue, Masson staining was used to observe fibrosis of lung tissue, and Western blot was used to detect protein expression levels of hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate kinase isozyme type M2 (PKM2), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), GSDMD-N-terminal domain (GSDMD-N), Caspase-1, interleukin-1β (IL-1β) and IL-18 in lung tissue. ELISA was used to detect contents of IL-1β and IL-18 in lung tissue. The results showed that, compared with the normal control group, there were no significant changes in all indexes in the normal+NaHS group, while the hypoxia group exhibited significantly increased mPAP and RVHI, thickened pulmonary vascular wall, narrowed lumen, increased collagen fibers, up-regulated expression levels of aerobic glycolysis-related proteins (HK2 and PKM2), up-regulated expression levels of pyroptosis-related proteins (NLRP3, GSDMD-N, Caspase-1, IL-1β, and IL-18), and increased contents of IL-1β and IL-18. These changes of the above indexes in the hypoxia group were significantly reversed by NaHS. These results suggest that H2S can improve rat HPH by inhibiting aerobic glycolysis-pyroptosis.
Animals
;
Rats, Sprague-Dawley
;
Male
;
Hypertension, Pulmonary/metabolism*
;
Glycolysis/drug effects*
;
Hydrogen Sulfide/therapeutic use*
;
Hypoxia/complications*
;
Rats
;
Pyroptosis/drug effects*
2.Exogenous administration of zinc chloride improves lung ischemia/reperfusion injury in rats.
Shu-Yuan WANG ; Jun-Peng XU ; Yuan CHENG ; Man HUANG ; Si-An CHEN ; Zhuo-Lun LI ; Qi-Hao ZHANG ; Yong-Yue DAI ; Li-Yi YOU ; Wan-Tie WANG
Acta Physiologica Sinica 2025;77(5):811-819
The aim of this study was to investigate the contribution of lung zinc ions to pathogenesis of lung ischemia/reperfusion (I/R) injury in rats. Male Sprague Dawley (SD) rats were randomly divided into control group, lung I/R group (I/R group), lung I/R + low-dose zinc chloride group (LZnCl2+I/R group), lung I/R + high-dose ZnCl2 group (HZnCl2+I/R group), lung I/R + medium-dose ZnCl2 group (MZnCl2+I/R group) and TPEN+MZnCl2+I/R group (n = 8 in each group). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of zinc ions in lung tissue. The degree of lung tissue injury was analyzed by observing HE staining, alveolar damage index, lung wet/dry weight ratio and lung tissue gross changes. TUNEL staining was used to detect cellular apoptosis in lung tissue. Western blot and RT-qPCR were used to determine the protein expression levels of caspase-3 and ZIP8, as well as the mRNA expression levels of zinc transporters (ZIP, ZNT) in lung tissue. The mitochondrial membrane potential (MMP) of lung tissue was detected by JC-1 MMP detection kit. The results showed that, compared with the control group, the lung tissue damage, lung wet/dry weight ratio and alveolar damage index were significantly increased in the I/R group. And in the lung tissue, the concentration of Zn2+ was markedly decreased, while the cleaved caspase-3/caspase-3 ratio and apoptotic levels were significantly increased. The expression levels of ZIP8 mRNA and protein were down-regulated significantly, while the mRNA expression of other zinc transporters remained unchanged. There was also a significant decrease in MMP. Compared with the I/R group, both MZnCl2+I/R group and HZnCl2+I/R group exhibited significantly reduced lung tissue injury, lung wet/dry weight ratio and alveolar damage index, increased Zn2+ concentration, decreased ratio of cleaved caspase-3/caspase-3 and apoptosis, and up-regulated expression levels of ZIP8 mRNA and protein. In addition, the MMP was significantly increased in the lung tissue. Zn2+ chelating agent TPEN reversed the above-mentioned protective effects of medium-dose ZnCl2 on the lung tissue in the I/R group. The aforementioned results suggest that exogenous administration of ZnCl2 can improve lung I/R injury in rats.
Animals
;
Reperfusion Injury/pathology*
;
Male
;
Rats, Sprague-Dawley
;
Rats
;
Chlorides/administration & dosage*
;
Lung/pathology*
;
Zinc Compounds/administration & dosage*
;
Apoptosis/drug effects*
;
Caspase 3/metabolism*
;
Cation Transport Proteins/metabolism*
3.Cost-Effectiveness of Denosumab for Treating Bone Metastases from Solid Tumors: A Systematic Review (2017-2023).
Cong WANG ; Jin-Yu LIU ; Min WAN ; Qi YUAN ; Yu ZHANG ; Guang-Yi YU ; Ru-Xu YOU
Chinese Medical Sciences Journal 2025;40(3):219-231
OBJECTIVES:
This systematic review examines recent pharmacoeconomic literature on denosumab' cost-effectiveness for bone metastasis treatment, providing evidence-based insights to guide healthcare policy decisions.
METHODS:
A comprehensive literature search was performed across Cochrane, PubMed, EMBASE (Ovid), CNKI, and Wanfang databases to identify original articles published between 2017 and 2023. Key words consisted of bone metastases, denosumab, and cost-effectiveness in the search strategy. The methodological quality of the included studies was assessed utilizing the revised Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022). Data was extracted regarding methodological characteristics and cost-effectiveness analyses.
RESULTS:
A total of 111 studies were retrieved, of which 6 met the inclusion criteria. All included studies were based on clinical trials and published literature data and exhibited high methodological quality. Up to 83% (5 out of 6) of comparisons demonstrated that denosumab was more cost-effective or dominant compared to zoledronic acid. The adjusted incremental cost-effectiveness ratios varied substantially by tumor type, ranging from CZK 436,339.09 to USD 136,234 per skeletal-related event avoided and from CZK 61,580.95 to USD 118,392.11 per quality-adjusted life year gained.
CONCLUSIONS
The majority of the included studies support denosumab as a more cost-effective treatment option for bone metastases in solid tumors compared to zoledronic acid. The application of CHEER (2022) enhances the reliability of pharmacoeconomic evaluations.
Denosumab/therapeutic use*
;
Humans
;
Bone Neoplasms/economics*
;
Cost-Benefit Analysis
4.Efficiency of chairside case-based learning in the prosthodontic clinic
Jingyi HUO ; Chunlan GUO ; Xinyuan ZHANG ; Pengyue YOU ; Xiaomin WU ; Kuo WAN ; Haitao DONG
Basic & Clinical Medicine 2025;45(9):1253-1257
Objective To evaluate the application of modified chairside case-based learning(CBL)in the teaching of dental residents in the prosthodontic clinic.Methods Dental residents in Peking Union Medical College Hospital from September 2022 to September 2024 were enrolled.Traditional CBL was conducted in control group.Modified chairside CBL was conducted in test group.The scores of department rotation examination and questionnaire results were analyzed with t-test statistical analysis.Results The score of"patient reception"in test group was significantly higher than control group(P<0.05).24 valid questionnaires were collected in two groups each.The rate of approval in test group was significantly higher than control group in the following items of questionnaire,including"reduce learning pressure or burden""improve the capacity of doctor-patient communication""improve the capacity of literature review""improve the capacity of group cooperation"(P<0.05).Conclusions Modified chairside CBL has showed good teaching effects in improving the capacity of patient reception,doctor-patient communication,literature review,group cooperation,and meanwhile reduced learning pressure or burden.
5.Exploring the need for head simulation teaching of stomatology in the eight-year medical doctor program of clinical medicine
Pengyue YOU ; Jiayi LI ; Chunlan GUO ; Xinyuan ZHANG ; Jingyi HUO ; Kuo WAN ; Haitao DONG
Basic & Clinical Medicine 2025;45(11):1528-1531
Objective To explore the need and evaluate the effectiveness for head-simulator in the teaching of sto-matology within the eight-year program of clinical medicine.Methods Questionnaire survey was conducted among the students from 2017 cohort of the eight-year program of clinical medicine at Peking Union Medical College.The survey results were statistically analyzed and described.Results Totally 87.9%of the students believed that incor-porating head-simulator into the clinical practice course of stomatology were necessary,and 93.9%expressed will-ingness to join the training.Most students preferred to practice peri-odontal scaling and cavity preparation for caries during the simulated training sessions.The majority of students considered two or four class hours of simulated head teaching to be reasonable.The pilot head simulation training was successfully implemented;75.0%of the students acknowledged clear teaching and convincible demonstrations.All the trainees agreed that the head simulation course helped them better understand stomatology knowledge,stimulated their interest in learning and expressed a desire for increased head simulation sessions during clinical practice course of stomatology.Additionally,87.5%of the students preferred head simulation training course to be applied in classic clinical clerkships.Conclusions There is strong demand among students of eight-year program of clinical medicine for incorporating head-simulator into the education of stomatology.The pilot simulation training received positive evaluations.Further exploration is needed to optimize specific scheduling and content arrangement.
6.Analysis of influencing factors on foot function recovery after distraction device-assisted repositioning of small incisions for Sanders type Ⅱ and Ⅲ calcaneal fractures
Bang-Yong ZONG ; Cai SONG ; Hao-Ran TIAN ; De-Yu WAN ; You-Fei FAN
Medical Journal of Chinese People's Liberation Army 2025;50(8):970-975
Objective To explore the influencing factors on foot function recovery after distraction device-assisted repositioning of small incisions treatment for Sanders Ⅱ and Ⅲ calcaneal fractures,and to provide guidance for timely clinical interventions.Methods A retrospective analysis was conducted on 80 patients with Sanders type Ⅱ and Ⅲ calcaneal fractures admitted to the People's Hospital of Bozhou from January 2021 to June 2023.Data were collected using a general information questionnaire,the hospital's electronic medical record system,the visual analog scale(VAS),the Marland foot function scale(MFS),the perceived social support scale(PSSS),and the perceived stress scale(PSS).The influencing factors of postoperative foot function recovery were analyzed using univariate factor analysis,multivariate linear regression,and structural equation modeling.Results The MFS scores of 80 patients at 6 months post-operation were significantly higher than preoperative scores(P<0.001).The rates of excellent,good,fair,and poor foot function at 6 months post-operation were 56.3%,31.3%,10.0%,and 2.5%,respectively.Univariate analysis revealed significant differences in MFS scores based on different ages,time to start full weight-bearing exercise,bone mineral density,surgical timing,body mass index(BMI),postoperative VAS score,PSSS score,PSS score,and the presence of postoperative peroneal muscle spasm and peroneal muscle tendon adhesion(P<0.05).Multivariate linear regression identified age,time to start full weight-bearing exercise,surgical timing,BMI,postoperative fibular muscle spasm,postoperative fibular muscle tendon adhesion,postoperative VAS score,PSSS score,and PSS score as significant factors affecting foot function recovery(P<0.05).Structural equation modeling indicated that age,time to start full weight-bearing exercise,bone density,operative timing,BMI,postoperative peroneal muscle spasm,postoperative peroneal tendon adhesion,and pain severity directly influenced postoperative foot functional recovery.Additionally,psychological stress not only directly affected postoperative foot functional recovery but also indirectly influenced it through the mediating effect of social support.Conclusions Foot function recovery after surgery for Sanders type Ⅱ and Ⅲ calcaneal fractures is influenced by multiple factors.Psychological stress not only directly affects the recovery of foot function after surgery,but also mitigates the harm to foot function through social support.
7.Long-term clinical outcomes after high and low ligations with lymph node dissection around the root of the inferior mesenteric artery in patients with rectal cancer
Min Wan LEE ; Sung Sil PARK ; Kiho YOU ; Dong Eun LEE ; Dong Woon LEE ; Sung Chan PARK ; Kyung Su HAN ; Dae Kyung SOHN ; Chang Won HONG ; Bun KIM ; Byung Chang KIM ; Hee Jin CHANG ; Dae Yong KIM ; Jae Hwan OH
Annals of Coloproctology 2024;40(1):62-73
Purpose:
This study aimed to evaluate the long-term clinical outcomes based on the ligation level of the inferior mesenteric artery (IMA) in patients with rectal cancer.
Methods:
This was a retrospective analysis of a prospectively collected database that included all patients who underwent elective low anterior resection for rectal cancer between January 2013 and December 2019. The clinical outcomes included oncological outcomes, postoperative complications, and functional outcomes. The oncological outcomes included overall survival (OS) and relapse-free survival (RFS). The functional outcomes, including defecatory and urogenital functions, were analyzed using the Fecal Incontinence Severity Index, International Prostate Symptom Score, and International Index of Erectile Function questionnaires.
Results:
In total, 545 patients were included in the analysis. Of these, 244 patients underwent high ligation (HL), whereas 301 underwent low ligation (LL). The tumor size was larger in the HL group than in the LL group. The number of harvested lymph nodes (LNs) was higher in the HL group than in the LL group. There were no significant differences in complication rates and recurrence patterns between the groups. There were no significant differences in 5-year RFS and OS between the groups. Cox regression analysis revealed that the ligation level (HL vs. LL) was not a significant risk factor for oncological outcomes. Regarding functional outcomes, the LL group showed a significant recovery in defecatory function 1 year postoperatively compared with the HL group.
Conclusion
LL with LNs dissection around the root of the IMA might not affect the oncologic outcomes comparing to HL; however, it has minimal benefit for defecatory function.
8.Clinical characteristics of 267 children with eosinophilic gastrointestinal disease:a multicenter study
Chun-Lei ZHAN ; Jie-Yu YOU ; Xiao-Qin LI ; Yong WANG ; Xian-Qin MEI ; Sheng-Hua WAN
Chinese Journal of Contemporary Pediatrics 2024;26(2):139-144
Objective To explore the clinical manifestations,endoscopic findings,histopathological changes,treatment,and prognosis of eosinophilic gastrointestinal disease(EGID)in children,with the aim of enhancing awareness among pediatricians about this condition.Methods Data of 267 children with EGID were prospectively collected from January 2019 to July 2022 at Jiangxi Children's Hospital,Hunan Children's Hospital,and Henan Children's Hospital.The age of onset,symptoms,physical signs,laboratory examination results,endoscopic findings,histopathological changes,and treatment outcomes were observed.Results Among the 267 children with EGID,the majority had mild(164 cases,61.4% )or moderate(96 cases,35.6% )clinical severity.The disease occurred at any age,with a higher prevalence observed in school-age children(178 cases).The main symptoms in infants were vomiting and hematemesis,while in toddlers,vomiting and bloody stools were prominent.Abdominal pain and vomiting were the primary symptoms in preschool and school-age children.Nearly half(49.4% )of the affected children showed elevated platelet counts on hematological examination,but there was no significant difference in platelet counts among children with mild,moderate,and severe EGID(P>0.05).Endoscopic findings in EGID children did not reveal significant specificity,and histopathological examination showed no specific structural damage.Among them,85.0% (227 cases)received acid suppression therapy,34.5% (92 cases)practiced dietary avoidance,20.9% (56 cases)received anti-allergic medication,and a small proportion(24 cases,9.0% )were treated with prednisone.Clinical symptoms were relieved in all patients after treatment,but three cases with peptic ulcers experienced recurrence after drug discontinuation.Conclusions Mild and moderate EGID are more common in children,with no specific endoscopic findings.Dietary avoidance,acid suppression therapy,and anti-allergic medication are the main treatment methods.The prognosis of EGID is generally favorable in children.[Chinese Journal of Contemporary Pediatrics,2024,26(2):139-144]
9.Determination of 19 components in Microctis Folium from different production areas based on UPLC-MS/MS
Min-you HE ; Li-wei WANG ; Lin LIU ; Po-yu ZHANG ; Jin-quan LAN ; Xin-ya WAN ; Zhen-yu LI ; Xiang-dong CHEN ; Dong-mei SUN
Acta Pharmaceutica Sinica 2024;59(5):1374-1381
The paper is to establish an UPLC-MS/MS method for the simultaneous determination of 19 components in Microctis Folium from different production areas. The 50% methanol was used as extraction solvent. The Agilent ZORBAX SB C18 (150 mm × 2.1 mm, 1.8 μm) column was used; mobile phase was acetonitrile - 0.1% acetic acid with gradient elution, flow rate was 0.3 mL·min-1, colume temperature was 30 ℃, and the injection volume was 2 μL; electrospray ionizaton source was used and detected in negative ion mode. The results showed that the established UPLC-MS/MS method could well separate the 19 components, and the methodological investigation results of 19 components were good. By means of orthogonal partial least squares discriminant analysis (OPLS-DA), 28 batches of Microctis Folium samples from different production areas can be divided into three categories, Guangdong, Guangxi and Hainan are each classified into one category, and 10 signature compounds which affecting the quality differences of different production areas were screened out. The established method is accurate, reliable, sensitive and reproducible. It can provide a basis for the establishment of the quality standard of Microctis Folium, as well as for safety and quality research.
10.The clinical correlations of gene polymorphism of methylenetetrahydrofolate reductase with Alzheimer's disease
Mengzhe YOU ; Xia ZHOU ; Wenwen YIN ; Ke WAN ; Zhongwu SUN
Acta Universitatis Medicinalis Anhui 2024;59(6):1081-1088
Objective To investigate the correlation between the methylenetetrahydrofolate reductase(MTHFR)C677T polymorphism and disease in the course of Alzheimer's disease(AD),as well as whether whether it is af-fected by APOE gene.Methods A total of 74 AD patients,85 aMCI patients and 81 healthy controls(HC)were included.The levels of serum homocysteine(Hcy),folate,and vitamin B12,as well as the genotypes of MTHFR C677T and APOE,were determined.Logistic regression analysis was conducted to explore the relationship between MTHFR C677T polymorphism and the risk of AD and aMCI,as well as in different APOE ε4 subgroups.Results Compared with HC group,the serum Hcy levels in AD group and aMCI group were significantly higher(P<0.001,P<0.001),while serum folate levels in aMCI group was significantly lower(P=0.017).The serum fo-late level was significantly lower(P=0.038)in individuals with the MTHFR TT genotype compared to those with CC and CT genotypes,while the serum Hcy level was significantly higher(P=0.002).Regression analysis showed that the MTHFR TT genotype might increase the risk of aMCI in the subgroup of APOE e4 non-carriers(OR=3.670,95%CI=1.077-12.509,P=0.038),but not in APOE e4 carriers.Conclusion MTHFR C677T polymorphism plays an important role in Hcy metabolism,which leads to increased serum Hcy levels and decreased folate levels.In APOE ε4 non-carriers,the MTHFR TT genotype may increase the risk of aMCI.


Result Analysis
Print
Save
E-mail