1.Effect and mechanism of BYL-719 on Mycobacterium tuberculosis-induced differentiation of abnormal osteoclasts
Jun ZHANG ; Jian GUO ; Qiyu JIA ; Lili TANG ; Xi WANG ; Abudusalamu·Alimujiang ; Tong WU ; Maihemuti·Yakufu ; Chuang MA
Chinese Journal of Tissue Engineering Research 2025;29(2):355-362
BACKGROUND:The phosphatidylinositol 3-kinase/protein kinase(PI3K/AKT)signaling pathway plays a pivotal role in regulating osteoclast activation,which is essential for maintaining bone homeostasis.Bone destruction in osteoarticular tuberculosis is caused by aberrant osteoclastogenesis induced by Mycobacterium tuberculosis infection.However,the role of the PI3K signaling pathway in Mycobacterium tuberculosis-induced aberrant osteoclastogenesis remains unclear. OBJECTIVE:To investigate the effects and mechanisms of the PI3K/AKT signaling pathway inhibitor BYL-719 on aberrant osteoclastogenesis induced by Mycobacterium tuberculosis. METHODS:RAW264.7 cells were infected with bovine Mycobacterium tuberculosis bacillus calmette-cuerin vaccine,and Ag85B was used for cellular immunofluorescence staining.The cell counting kit-8 assay was employed to determine the safe concentration of BYL-719.There were four groups in the experiment:blank control group,BYL-719 group,BCG group,and BCG+BYL-719 group.Under the induction of receptor activator of nuclear factor kappa-B ligand,the effects of BYL-719 on post-infection osteoclast differentiation and fusion were explored through tartrate-resistant acid phosphatase staining and phalloidin staining.RT-PCR and western blot were used to detect the expression of osteoclast-related genes and proteins,and further investigate the mechanism of action. RESULTS AND CONCLUSION:Immunofluorescence staining showed that RAW264.7 cells phagocytosed Mycobacterium tuberculosis.Cell counting kit-8 data indicated that 40 nmol/L BYL-719 was non-toxic to cells.Tartrate-resistant acid phosphatase staining and phalloidin staining showed that BYL-719 inhibited the generation and fusion ability of osteoclasts following infection.RT-PCR and western blot results also indicated that BYL-719 suppressed the upregulation of osteoclast-specific genes(including c-Fos,NFATc1,matrix metalloproteinase 9,and CtsK)induced by Mycobacterium tuberculosis infection(P<0.05).Western blot and immunofluorescence staining revealed that BYL-719 inhibited excessive osteoclast differentiation induced by Mycobacterium tuberculosis by downregulating the expression of IκBα-p65.To conclude,BYL-719 inhibits aberrant osteoclastogenesis induced by Mycobacterium tuberculosis through the downregulation of IκBα/p65.Therefore,the IκBα/p65 signaling pathway is a potential therapeutic target for osteoarticular tuberculosis,and BYL-719 holds potential value for the preventing and amelioration of bone destruction in osteoarticular tuberculosis.BYL-719 has the potential to prevent and ameliorate bone destruction in osteoarticular tuberculosis.
2.Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population
Xiheng CHEN ; Siming GUI ; Dachao WEI ; Dingwei DENG ; Yudi TANG ; Jian LV ; Wei YOU ; Jia JIANG ; Jun LIN ; Huijian GE ; Peng LIU ; Yuhua JIANG ; Lixin MA ; Yunci WANG ; Ming LV ; Youxiang LI
Journal of Stroke 2025;27(2):237-249
Background:
and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture.
Methods:
A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture.
Results:
The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05).
Conclusion
The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.
3.Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population
Xiheng CHEN ; Siming GUI ; Dachao WEI ; Dingwei DENG ; Yudi TANG ; Jian LV ; Wei YOU ; Jia JIANG ; Jun LIN ; Huijian GE ; Peng LIU ; Yuhua JIANG ; Lixin MA ; Yunci WANG ; Ming LV ; Youxiang LI
Journal of Stroke 2025;27(2):237-249
Background:
and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture.
Methods:
A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture.
Results:
The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05).
Conclusion
The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.
4.Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population
Xiheng CHEN ; Siming GUI ; Dachao WEI ; Dingwei DENG ; Yudi TANG ; Jian LV ; Wei YOU ; Jia JIANG ; Jun LIN ; Huijian GE ; Peng LIU ; Yuhua JIANG ; Lixin MA ; Yunci WANG ; Ming LV ; Youxiang LI
Journal of Stroke 2025;27(2):237-249
Background:
and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture.
Methods:
A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture.
Results:
The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05).
Conclusion
The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.
5.Proximal femoral nail antirotation for femoral intertrochanteric fractures with lateral wall integrity and lateral wall risk
Zhonghan WU ; Jingkun WANG ; Tao LI ; Xinzhong XU ; Shuisheng YU ; Li CHENG ; Dasheng TIAN ; Jian TANG ; Juehua JING
Chinese Journal of Tissue Engineering Research 2024;28(6):911-916
BACKGROUND:For elderly patients with traumatic hip fractures,the related factors of prognosis are very complex,and the integrity of the lateral wall is one of the influencing factors.It is of important clinical value to understand the effect of lateral wall injury on the prognosis of femoral intertrochanteric fracture. OBJECTIVE:To evaluate the relationship between the integrity of the lateral wall and hip functional recovery and other outcomes in patients with femoral intertrochanteric fractures. METHODS:Totally 82 patients with femoral intertrochanteric fractures were screened and all patients received proximal femoral nail antirotation fixation.According to the thickness of the lateral wall,the patients were divided into the lateral wall intact group(n=31)and lateral wall risk group(n=51).The perioperative indexes,weight-bearing time,fracture healing time,hip joint function and range of motion,postoperative pain and complications were compared between the two groups. RESULTS AND CONCLUSION:(1)The time of hospitalization and the number of fluoroscopies during operation in the lateral wall intact group were significantly lower than those in the lateral wall risk group(P<0.05),but there was no significant difference in other perioperative indexes.(2)Both groups were able to get down to the ground early after surgery and finally complete weight-bearing,but in the lateral wall risk group,the time of fracture healing was longer;the time of complete weight-bearing was significantly delayed;the Harris score of the last follow-up was lower;the range of motion of hip extension and flexion and neck trunk angle on the affected side were smaller(P<0.05).(3)There was no significant difference in the incidence of postoperative complications between the two groups,but the overall incidence of complications in the lateral wall intact group was significantly lower(P<0.05).(4)In summary,after internal fixation of proximal femoral nail antirotation,patients with the intact lateral wall had a relatively better prognosis than those with risk lateral wall.
6.Epidemiological investigation of a brucellosis outbreak transmitted through a lamb slaughtering site
ZHANG Hongfang ; WANG Guohua ; LIU Jian ; QIAN Hua ; TANG Tao
Journal of Preventive Medicine 2024;36(10):887-888,892
Abstract
On August 11, 2022, Tongxiang Center for Disease Control detected a case of brucellosis, and the case was not engaged in related work. Case finding and risk factor investigation were immediately conducted to trace the source of infection. It was revealed that the case sold aquatic products at a farmer's market and frequently picked up goods at a seafood warehouse adjacent to a lamb slaughtering site. There was a potential risk of infection due to indirect contact with slaughtered lambs or contaminants. Serological tests were conducted on 9 employees of the slaughtering site and 48 residents nearby, and the brucellosis cases diagnosed in hospitals in the same area were searched. A total of 11 brucellosis cases were identified, including 9 confirmed cases and 2 asymptomatic infections. There were 2 cases of slaughtering workers and 9 cases of non-occupational individuals from the surrounding area of the slaughtering site. Brucella melitensis biovar 3 were isolated from a slaughtering worker and a non-occupational individual. The slaughtered lambs primarily came from northern regions such as Inner Mongolia and Heilongjiang. It was concluded that it was a cluster caused by Brucella melitensis biovar 3 and spread through direct or indirect contact with imported infected lambs or contaminated environments from a lamb slaughtering site. It is suggested to strengthen the quarantine of imported sheep, legally shut down non-compliant lamb slaughtering sites, implement designated slaughtering and enhance occupational protection.
7.Spectrum-effect relationship combined with bioactivity evaluation to discover the main antidepressant active components of Baihe Dihuang decoction
Chao HU ; Hong-qing ZHAO ; Jian LIU ; Lu WANG ; Lei YANG ; Shui-han ZHANG ; Lin TANG
Acta Pharmaceutica Sinica 2024;59(5):1364-1373
The study utilized spectral correlation analyses combined with bioactivity evaluation to examine the effective components of antidepressants in the Baihe Dihuang decoction. Firstly, the chemical fingerprints for different extraction parts in the Baihe Dihuang decoction were achieved using HPLC and UHPLC-MS technology. Then, in order to evaluate the antidepressant effect of Baihe Dihuang decoction, the animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Hunan University of Chinese Medicine (No. LLBH-202104270001), in compliance with the Institutional Animal Care Guidelines. We recorded the distance of autonomous movement of mice in open field experiment, the immobility time of tail suspension test, and the forced swimming. Additionally, we measured the content of neurotransmitters. Finally, Pearson analysis, grey correlation analysis, and orthogonal partial least squares regression analysis were utilized to establish the correlation between antidepressant efficacy indicators and fingerprinting. The spectrum-effect relationship results were confirmed through the in vitro activity verification. This study demonstrated that regaloside A, B, C, catalpol, and Isoacteoside might be the main antidepressant components in Baihe Dihuang decoction. Furthermore, it was found that using diverse mathematical models and bioactivity evaluation could enhance the accuracy of the spectral correlation analyses results.
8.Incidence and risk factors of deep vein thrombosis in patients with rheumatoid arthritis
Xiaofei TANG ; Yonghong LI ; Qiuling DING ; Zhuo SUN ; Yang ZHANG ; Yumei WANG ; Meiyi TIAN ; Jian LIU
Journal of Peking University(Health Sciences) 2024;56(2):279-283
Objective:To investigate the incidence and risk factors of deep vein thrombosis(DVT)in patients with rheumatoid arthritis(RA).Methods:The clinical data of RA patients who were hospi-talized in the Department of Rheumatology and Immunology of Aerospace Center Hospital from May 2015 to September 2021 was retrospectively analyzed,including demographic characteristics,concomitant diseases,laboratory examinations(blood routine,biochemistry,coagulation,inflammatory markers,rheumatoid factor,antiphospholipid antibodies and lupus anticoagulant,etc.)and treatment regimens.The patients were compared according to the presence or absence of DVT,and the t test,Mann-Whitney U test or Chi-square test were applied to screen for relevant factors for DVT,followed by Logistic regres-sion analysis to determine risk factors for DVT in patients with RA.Results:The incidence of DVT in the RA patients was 9.6%(31/322);the median age of RA in DVT group was significantly older than that in non-DVT group[64(54,71)years vs.50(25,75)years,P<0.001];the level of disease activity score using 28 joints(DAS28)-erythrocyte sedimentation rate(ESR)in DVT group was higher than that in non-DVT group[5.2(4.5,6.7)vs.4.5(4.5,5.0),P<0.001];the incidence of hypertension,chronic kidney disease,fracture or surgery history within 3 months,and varicose veins of the lower ex-tremities in DVT group was higher than that in non-DVT group(P<0.001).The levels of hemoglobin and albumin in DVT group were significantly lower than that in non-DVT group(P=0.009,P=0.004),while the D-dimer level and rheumatoid factor positive rate in DVT group were significantly higher than that in non-DVT group(P<0.001).The use rate of glucocorticoid in DVT group was higher than that in non-DVT group(P=0.009).Logistic regression analysis showed that the age(OR=1.093,P<0.001),chronic kidney disease(OR=7.955,P=0.005),fracture or surgery history with-in 3 months(OR=34.658,P=0.002),DAS28-ESR(OR=1.475,P=0.009),and the use of glu-cocorticoid(OR=5.916,P=0.003)were independent risk factors for DVT in RA patients.Conclu-sion:The incidence of DVT in hospitalized RA patients was significantly increased,in addition to tradi-tional factors,such as age and chronic kidney disease,increased DAS28-ESR level and the use of glu-cocorticoid were also independent risk factors for DVT.
9.Expert consensus on the evaluation and management of dysphagia after oral and maxillofacial tumor surgery
Xiaoying LI ; Moyi SUN ; Wei GUO ; Guiqing LIAO ; Zhangui TANG ; Longjiang LI ; Wei RAN ; Guoxin REN ; Zhijun SUN ; Jian MENG ; Shaoyan LIU ; Wei SHANG ; Jie ZHANG ; Yue HE ; Chunjie LI ; Kai YANG ; Zhongcheng GONG ; Jichen LI ; Qing XI ; Gang LI ; Bing HAN ; Yanping CHEN ; Qun'an CHANG ; Yadong WU ; Huaming MAI ; Jie ZHANG ; Weidong LENG ; Lingyun XIA ; Wei WU ; Xiangming YANG ; Chunyi ZHANG ; Fan YANG ; Yanping WANG ; Tiantian CAO
Journal of Practical Stomatology 2024;40(1):5-14
Surgical operation is the main treatment of oral and maxillofacial tumors.Dysphagia is a common postoperative complication.Swal-lowing disorder can not only lead to mis-aspiration,malnutrition,aspiration pneumonia and other serious consequences,but also may cause psychological problems and social communication barriers,affecting the quality of life of the patients.At present,there is no systematic evalua-tion and rehabilitation management plan for the problem of swallowing disorder after oral and maxillofacial tumor surgery in China.Combining the characteristics of postoperative swallowing disorder in patients with oral and maxillofacial tumors,summarizing the clinical experience of ex-perts in the field of tumor and rehabilitation,reviewing and summarizing relevant literature at home and abroad,and through joint discussion and modification,a group of national experts reached this consensus including the core contents of the screening of swallowing disorders,the phased assessment of prognosis and complications,and the implementation plan of comprehensive management such as nutrition management,respiratory management,swallowing function recovery,psychology and nursing during rehabilitation treatment,in order to improve the evalua-tion and rehabilitation of swallowing disorder after oral and maxillofacial tumor surgery in clinic.
10.Expert consensus on cryoablation therapy of oral mucosal melanoma
Guoxin REN ; Moyi SUN ; Zhangui TANG ; Longjiang LI ; Jian MENG ; Zhijun SUN ; Shaoyan LIU ; Yue HE ; Wei SHANG ; Gang LI ; Jie ZHNAG ; Heming WU ; Yi LI ; Shaohui HUANG ; Shizhou ZHANG ; Zhongcheng GONG ; Jun WANG ; Anxun WANG ; Zhiyong LI ; Zhiquan HUNAG ; Tong SU ; Jichen LI ; Kai YANG ; Weizhong LI ; Weihong XIE ; Qing XI ; Ke ZHAO ; Yunze XUAN ; Li HUANG ; Chuanzheng SUN ; Bing HAN ; Yanping CHEN ; Wenge CHEN ; Yunteng WU ; Dongliang WEI ; Wei GUO
Journal of Practical Stomatology 2024;40(2):149-155
Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.


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