OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside （TWM） on nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via the tail vein. The modeling rats were randomly divided into the model group （distilled water）， prednisone group （10 mg/kg）， and TWM high- and low-dose groups （10 and 5 mg/kg， respectively）. Additionally， blank group （distilled water） without model induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled water by gavage， once a day， for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed； the levels of 24-hour urinary protein （24 h-UTP） and serum biochemical indicators [albumin （ALB）， blood urea nitrogen （BUN）， serum creatinine （SCr）， cholesterol （CHOL）， and triglyceride （TG）] in rats were determined； the levels of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in kidney tissue of rats were determined； expressions of hypoxia-inducible factor-1α （HIF-1α）/microRNA-155-5p （miR-155-5p）/nuclear factor erythriod 2- related factor 2 （Nrf2） signaling pathway-related mRNA and protein in the renal tissues of rats were detected. RESULTS Compared with the blank group， the rats in the model group exhibited disordered renal tissue structure， with a small amount of glomerular necrosis and edema of the renal tubular epithelial cells. 24 h-UTP， serum levels of SCr， BUN， CHOL and TG， MDA content， mRNA and protein expressions of HIF-1α and Keap1 as well as the expression of miR-155-5p in renal tissues were increased significantly （ P ＜0.05）. Serum level of ALB， SOD level in renal tissue as well as mRNA and protein expressions of Nrf2 were decreased significantly （ P ＜0.05）. Compared with the model group， TWM high-dose and low-dose groups exhibited significant improvements in renal injury， with notable reversals in the levels of the above quantitative indicators （ P ＜0.05）. CONCLUSIONS TWM can alleviate oxidative stress-induced damage and thereby improve nephrotic syndrome in rats by regulating the HIF-1α/miR-155-5p/Nrf2 signaling pathway.

Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

Objective:To analyze the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with main splenic artery embolization in the treatment of patients with portal hypertension upper gastrointestinal bleeding complicated with extensive portal vein thrombosis (PVT).Methods:This study was a prospective, single-center, open-label, single-arm clinical trial. In the first phase, 81 patients with portal hypertension upper gastrointestinal bleeding who were admitted to Beijing Shijitan Hospital, Capital Medical University from January 2018 to December 2018 were consecutively enrolled, including 57 males and 24 females, with the age of (51.3±10.4) years. During TIPS surgery, the pressure of the portal vein before and after the balloon blocking the splenic artery was measured to clarify the contribution of the splenic artery to portal hypertension. In the second stage, from January 2019 to December 2022, 104 patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT were re-enrolled, including 71 males and 33 females, with the age of (50.9±12.5) years. TIPS combined with main splenic artery embolization was performed, and portal vein pressure was measured before and after embolization. Follow up on the postoperative esophageal and gastric varices of the patients in the second stage.Results:The portal vein pressures before and after the first stage of balloon occlusion of the splenic artery were (35.2±8.4) mmHg (1 mmHg=0.133 kPa) and (24.2±6.3) mmHg, respectively. The pressure after occlusion was lower than that before occlusion, and the difference was statistically significant ( t=10.54, P<0.001). The portal vein pressures before and after the second stage embolization were (36.1±9.5) mmHg and (21.1±4.7) mmHg respectively. The pressure after embolization was lower than that before embolization, and the difference was statistically significant ( t=13.47, P<0.001). In the second stage, among the 104 patients, the proportion of those whose varicose veins disappeared or improved 6 months after the operation was 43.3%(45/104) and 51.0%(53/104), respectively. There were no patients with aggravation or rebleeding due to rupture. One year later, 8 patients (7.7%) had aggravated or ruptured esophageal and gastric varices with bleeding. Two years later, 12 patients (11.5%) had aggravated or bleeding. Conclusion:TIPS combined with main splenic artery embolization can effectively reduce the portal vein pressure in patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT, improve the degree of esophageal and gastric varices, and reduce the risk of gastrointestinal bleeding.

Epidemiology research has found that ABO blood group and the gene coding ABO glycosyltransferases are associated with many human diseases. The activity of ABO glycosyltransferases varies with different blood types, mediating different glycosylation modifications. The variation in glycosylation level might be the risk factor of specific disease. Based on the literature retrieval and analysis, glycosylation levels regulated by ABO glycosyltransferases mainly affect the ABH blood group antigens and von Willebrand factor (vWF). By modulating key glycosylation components, ABO glycosyltransferases partly determine the activity or expression levels of the ABH antigens and vWF, thereby affecting the development and progression of diseases. Exploring the pathogenic mechanisms of ABO glycosyltransferases can improve the understanding of the molecular pathology of related diseases and provide reference for clinical research and application.

Objective:To investigate the safety and efficacy of urinary microbiota transplantation（UMT）in treating interstitial cystitis（IC）.Methods:A retrospective analysis of the clinical data of three patients with IC treated with UMT at the Central Hospital of Jiangnan University from May 2022 to August 2024. Three women（45，62，79 years）presented with urinary frequency（10 - 90 min intervals），urgency，dysuria，lower abdominal pain，and non-organic sleep disorder，with nocturia（2 - 15 episodes）causing sleep difficulty. Disease durations were 3，6，and 21 years. Prior antibiotic therapy failed. Preoperative urinalysis/culture（x2）ruled out bacterial cystitis，and diagnosed as interstitial cystitis（IC），with one of transient positive urine culture. Preoperative scores for case 1 were self-rating depression scale（SDS）of 49，self-rating anxiety scale（SAS）of 31，interstitial cystitis symptom index（ICSI）of 5，interstitial cystitis problem index（ICPI）of 2，brief urological problem scale of 50，genitourinary pain assessment scale of 10，and pain catastrophizing scale（PCS）of 0. For case 2，the scores were 60 of SDS，66 of SAS，9 of ICSI，11 of ICPI，50 of brief urological problem scale，28 of genitourinary pain assessment scale，and 34 of PCS. For case 3，the scores were 44 of SDS，48 of SAS，11 of ICSI，5 of ICPI，33 of brief urological problem scale，27 of genitourinary pain assessment scale，and 21 of PCS. Preoperative bladder hydro-distention showed mucosal hemorrhage including central block hemorrhage（Case 1），numerous spots（Case 2），and distinct sheets（Case 3）. Preoperative urine 16S rRNA sequencing revealed low diversity，increased Gardnerella/ Bacteroides（opportunistic），and decreased Bacillus/ Streptococcus（beneficial）. Two healthy young female donors had normal comprehensive tests covering blood/urine/stool，coagulation，CRP，immunity，liver/kidney function，lipids，infectious diseases，hormones，tumor markers，urine culture，TOUCH，and expanded quantitative urine culture. Donor urine 16S rRNA showed low pathogenic（ Gardnerella/ Bacteroides）abundance. Donor midstream morning urine was catheter-collected，centrifuged，and the bacterial pellet resuspended in saline. Recipients underwent bladder irrigation pre-UMT. On UMT day，donor bacterial suspension was instilled via catheter with adverse event monitoring. Follow-up included clinic visits at 1 month and 1 year for symptom assessment，scale scoring，cystoscopy evaluating mucosal inflammation，hydrodistension checks，and telephone tracking of urinary symptoms every 2 - 3 months. Prognosis was assessed by symptom relief，scale score reduction，and mucosal recovery. Results:No adverse reactions occurred within 24 hours post-UMT in all 3 cases. Two patients showed same-day urinary urgency reduction；three reported relief from urinary frequency/urgency on postoperative day 7，with 2 - 3 hour daytime intervals and 0 - 5 nocturnal voids. Two patients experienced lower abdominal pain alleviation. Postoperative Week 1 urinalysis and urine cultures revealed no abnormalities. The 16S rRNA test showed a decrease in the abundance of harmful bacteria（e.g.， Cupriavidus，Ureaplasm，Mycobacterium，Pseudomonas）and an increase in the abundance of beneficial bacteria（ Dietzia，Halomonas，and Streptococcus），and the overall urobacterial structure was significantly improved and similar to that of the donor. Case 1 was followed up for 20 months，and the lab tests were normal，with SDS scales of 38，SAS of 20，ICSI of 3，ICPI of 2，brief urological problem scale of 44，genitourinary pain assessment scale of 10，PCS of 0，at 9 months post-op follow-up，indicating physical and mental improvement. The bladder hydro-distention revealed intact mucosa with only mild inflammation，which improved versus preoperative situation. Case 2 was followed up for 15 months，and the lab tests were normal，with SDS scales of 44，SAS of 34，ICSI of 4，ICPI of 2，brief scale of urinary problems of 0，genitourinary pain assessment scale of 9，PCS of 7，at 2 months post-op follow-up，showing improved anxiety/depression and quality of life. The hydro-distention showed decreased scattered hemorrhagic dots and mucosal inflammation. Case 3 was followed up for 13 months，with an increased leukocytes of urine and the other being normal for lab tests，and SDS scales of 35，SAS of 46，ICSI of 13，ICPI of 13，brief scale of urinary problems of 10，genitourinary pain assessment scale of 33，PCS of 11，at 13 months post-op follow-up，indicating physical and mental improvement. The hydro-distention revealed mucosal congestion，marked submucosal vasodilation，and inflammation decreased compared with preoperative situation. Conclusions:UMT alleviates urinary frequency，urgency，and pain in IC patients with sustained effects，significantly improves urine microecology，and shows no adverse events，positioning it as a viable intervention for IC.

Objective:To evaluate the outcomes of intensive conservative treatment compared to conventional conservative treatment in patients with acute aortic syndrome(AAS).Methods:The study prospectively enrolled consecutive patients with AAS who were admitted to Beijing Anzhen Hospital, affiliated with Capital Medical University, and Beijing Dawanglu Emergency Rescue Hospital from January 2024 to December 2024. These patients with surgical contraindications or refused surgery for various reasons opted for conservative treatment. A total of 282 patients were included, and 15 patients with missing data or those who died without any treatment were excluded. Finally, 267 patients were enrolled, of whom 94 received intensive conservative treatment, and 173 received conventional conservative treatment, the inverse probability of treatment weighting (IPTW) was used to reduce the influence of confoundings. After adjusting of baseline datas via IPTW, the survival outcomes of the two groups were compared at 14 days, 30 days, and at the end of follow-up.Results:The results showed significant differences in acute phase survival rates between the enhanced conservative treatment group and the conventional conservative treatment group at 14 days(82.40%vs.53.20%, P<0.0001). Significant survival differences were also observed at 30 days and at 276-day mid-term follow-up (96.29% vs.51.60%, P<0.0001; 78.50% vs.48.50%, P<0.0001). In the subgroup analysis, for type A aortic dissection, the enhanced conservative treatment group had higher survival rates compared to the conventional conservative treatment group at 14, 30 and 276 days (63.46% vs.41.35%, P<0.05; 52.17% vs.37.90%, P<0.05; 50.00% vs. 31.97%, P<0.05). However, for type B aortic dissection, although the enhanced conservative treatment group had higher survival rates than the conventional conservative treatment group, no statistically significant differences were observed (96.29% vs. 80.00%, P=0.054; 95.65% vs.78.37%, P=0.067; 94.12% vs.74.20%, P=0.088). Conclusion:For patients diagnosed with AAS are forced to choose conservative treatment if emergency surgery is not possible in the first place, intensive conservative treatment strategies can significantly reduce the mortality in the acute phase compared with conventional conservative treatment. Mid-term follow-up, intensive conservative treatment still has a significant survival advantage.

Breast cancer is the most prevalent malignant tumor that poses a threat to women's health in China,with incidence and mortality rates persistently increasing.Given this critical situation,there is an urgent need to optimize therapeutic options through basic translational research to address current treatment challenges.This article provided a comprehensive overview of the significant advancements in fundamental translational breast cancer research in China over the past five years,aiming to provide a scientific basis and new directions for precision treatment of breast cancer.This research encompasses a range of subjects,including molecular typing,biomarker identification,exploration of drug resistance mechanisms,optimization of precision treatment strategies,and identification of new targets in breast cancer.In the domain of molecular typing,researchers have revealed substantial disparities in treatment responses among distinct subtypes of breast cancer through in-depth analysis.This has led to the proposal of specific therapeutic strategies for each subtype,thereby establishing a robust theoretical foundation for individualized treatment approaches.The identification of biomarkers plays a pivotal role in selecting appropriate treatment options for patients.Recent research advancements have demonstrated the potential of liquid biopsy and proteomics technologies in uncovering promising biomarkers,offering novel prospects for the early diagnosis and prognostic assessment of breast cancer.In the investigation of resistance mechanisms,researchers have elucidated the molecular underpinnings of resistance to endocrine therapy and human epidermal growth factor receptor 2(HER2)-targeted therapy and proposed potential strategies to overcome resistance.This has paved the way for novel approaches to enhance therapeutic efficacy.In the context of immunotherapy and targeted therapies,the discernment of novel targets and biomarkers has facilitated novel perspectives on breast cancer treatment.Based on advanced comprehension of tumor heterogeneity,researchers constantly optimize precision treatment strategies through multiomics analysis,thus offering patients with breast cancer enhanced personalized treatment options.Concurrently,the implementation of novel technologies has been instrumental in facilitating the advancement of precision treatment for breast cancer.For instance,the application of artificial intelligence technology has demonstrated considerable potential in the early screening,diagnosis,efficacy assessment and prognosis prediction of breast cancer.Conversely,the advent of innovative drug delivery systems facilitated by nanotechnology has led to enhanced targeting and efficacy of pharmaceutical agents.Furthermore,research into hydrogel patch technology and tumor vaccines has yielded novel strategies for the treatment of breast cancer.Overall,China has accomplished remarkable achievements in the field of basic translational research on breast cancer.These findings not only enhance our understanding of the molecular mechanisms of breast cancer,but also provide new directions and hope for the development of future therapeutic strategies.With the advancement of multidisciplinary integration and the application of new emerging technologies,precision therapy is expected to provide more benefits to breast cancer patients.

OBJECTIVES: This study aims to analyze the clinical symptoms and imaging manifestations in patients with temporomandibular disorder syndrome (TMD), who are sensitive to sudden temperature drop. METHODS: One hundred and nineteen patients with TMD who attended the Department of Stomatology of the First Medical Center of Chinese People's Liberation Army General Hospital from December 2022 to December 2023 were included, including 44 males and 75 females, with a mean age of 32.4±13.7 years.The questionnaire was used to determine whether they were sensitive to temperature drop, and the TMD patients were divided into a temperature plunge-sensitive group and a temperature drop insensitive group. The clinical symptoms and imaging manifestations of patients in the two groups were observed. SPSS 25.0 was used for statistical analysis. RESULTS: There was no statistically significant difference between the gender and age of patients in the temperature plunge-sensitive group (50 patients) and the insensitivity group (69 patients) (P>0.05). The percentage of patients with pain was slightly higher in the temperature plunge-sensitive group [86.0% (43/50)] than in the insensitive group [68.1% (47/69)], and the difference was statistically significant (χ²=5.031, P=0.025), while the differences in joint murmur and mouth opening limitation between the two groups were not statistically significant. A total of 238 lateral joints were detected in both groups, the percentage of osteoarthropathic imaging changes was significantly higher in the temperature plunge-sensitive group [82.0% (82/100)] than in the insensitive group [53.6% (74/138)] (χ²=20.675, P<0.001). Magnetic imaging showed that the percentage of joint effusion was higher in patients in the temperature plunge-sensitive group [66.0% (33/50)] than in the insensitive group [42.0% (29/69)], and the difference was statistically significant (χ²=5.602, P=0.018). CONCLUSIONS TMD patients with maxillofacial pain symptoms, joint effusions, and abnormal imaging of osteoarticular structures are more likely to be sensitive to sudden temperature drops.
Humans ; Male ; Female ; Adult ; Temporomandibular Joint Disorders/diagnosis* ; Surveys and Questionnaires ; Middle Aged ; Young Adult ; Temperature ; Adolescent

OBJECTIVES: This study aimed to investigate the correlation between clinical symptoms and unilateral chewing habits in patients with temporomandibular disorder (TMD) accompanied by tinnitus. METHODS: A total of 285 patients diagnosed with TMD at the Department of Stomatology of the First Medical Center of Chinese People's Liberation Army General Hospital between December 2020 and May 2024 were included and divided into two groups: tinnitus group and non-tinnitus group. Analysis was conducted on the proportion of patients with unilateral chewing habits in both groups, the correlation between the side of tinnitus and the side of unilateral chewing, and the correlation of tinnitus with TMD clinical symptoms (joint clicking, joint pain, and limited mouth opening) and unilateral chewing habits. The correlation of the type of disc displacement with unilateral chewing and tinnitus was also examined. RESULTS: In the tinnitus group, the proportions of patients with and without unilateral chewing habits were 90.70% (39/43) and 9.30% (4/43), respectively. In the non-tinnitus group, the proportions of patients with and without unilateral chewing habits were 76.03% (184/242) and 23.97% (58/242), respectively. The proportion of patients with unilateral chewing habits in the tinnitus group was significantly higher than in the non-tinnitus group (χ²=4.613, P<0.05). Correlation analysis showed a positive correlation between tinnitus and unilateral chewing habits (P<0.05). In the left-sided tinnitus group, the proportion of left-sided unilateral chewers [54.55% (12/22)] was higher than that of right-sided unilateral chewers [45.45% (10/22)]. In the right-sided tinnitus group, the proportion of right-sided unilateral chewers [81.82% (9/11)] was higher than that of left-sided unilateral chewers [18.18% (2/11)]. The difference was statistically significant (χ²=7.282, P<0.05). A positive correlation was also found between the side of tinnitus and the side of unilateral chewing habits (P<0.05). The proportion of patients with pain was significantly higher in the tinnitus group than in the non-tinnitus group (P<0.05). No significant difference in the proportion of joint clicking or limited mouth opening and disc displacement (no disc displacement, unilateral disc displacement, bilateral disc displacement, reducible disc displacement, or irreducible disc displacement) was found between the tinnitus and non-tinnitus groups (P>0.05). CONCLUSIONS TMD with unilateral chewing habits may be a contributing factor to unexplained tinnitus. Unexplained tinnitus is correlated with joint pain in patients with TMD.
Humans ; Tinnitus/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Mastication ; Male ; Adult ; Female ; Middle Aged ; Habits