BACKGROUND: The role of inflammation in the development of gestational diabetes mellitus (GDM) has recently become a focus of research. The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI), novel indices, reflect the body's chronic immune-inflammatory state. This study aimed to investigate the associations between the SII or SIRI and GDM. METHODS: A prospective birth cohort study was conducted at Beijing Obstetrics and Gynecology Hospital from February 2018 to December 2020, recruiting participants in their first trimester of pregnancy. Baseline SII and SIRI values were derived from routine clinical blood results, calculated as follows: SII = neutrophil (Neut) count × platelet (PLT) count/lymphocyte (Lymph) count, SIRI = Neut count × monocyte (Mono) count/Lymph count, with participants being grouped by quartiles of their SII or SIRI values. Participants were followed up for GDM with a 75-g, 2-h oral glucose tolerance test (OGTT) at 24-28 weeks of gestation using the glucose thresholds of the International Association of Diabetes and Pregnancy Study Groups (IADPSG). Logistic regression was used to analyze the odds ratios (ORs) (95% confidence intervals [CIs]) for the the associations between SII, SIRI, and the risk of GDM. RESULTS: Among the 28,124 women included in the study, the average age was 31.8 ± 3.8 years, and 15.76% (4432/28,124) developed GDM. Higher SII and SIRI quartiles were correlated with increased GDM rates, with rates ranging from 12.26% (862/7031) in the lowest quartile to 20.10% (1413/7031) in the highest quartile for the SII ( Ptrend <0.001) and 11.92-19.31% for the SIRI ( Ptrend <0.001). The ORs (95% CIs) of the second, third, and fourth SII quartiles were 1.09 (0.98-1.21), 1.21 (1.09-1.34), and 1.39 (1.26-1.54), respectively. The SIRI findings paralleled the SII outcomes. For the second through fourth quartiles, the ORs (95% CIs) were 1.24 (1.12-1.38), 1.41 (1.27-1.57), and 1.64 (1.48-1.82), respectively. These associations were maintained in subgroup and sensitivity analyses. CONCLUSION The SII and SIRI are potential independent risk factors contributing to the onset of GDM.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/immunology* ; Prospective Studies ; Adult ; Inflammation/immunology* ; Glucose Tolerance Test ; Birth Cohort

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

Objective T o explore the correlation between adult chest CT quantitative parameters and traditional Chinese medicine(TCM)constitution classification in adult persons with different body mass index(BMI).Methods The basic information of 205 adult subjects in the hospital was collected,including gender,age,height,weight,BMI,etc.They were divided into the low body mass group(BMI＜18.5 kg/mi2),normal body mass group(BMI 18.5-＜24.0 kg/m2)and overweight/obese group(BMI≥24.0 kg/m2)according to BMI.All subjects underwent the TCM constitution classification.The distribution of TCM constitutions a-mong the three groups with different BMI was analyzed.The quantitative chest CT parameters were collected,including fat content,muscle content,area of the middle slice of the transverse section image,transverse diam-eter,anteroposterior diameter,scan length,etc.The differences were compared among different TCM constitu-tions,individual basic information and chest CT quantitative parameters.Results In the low BMI group,the Qi-stagnation constitution was the highest;in the BMI normal group,the gentler constitution was the highest,while in the overweight/obese group,the phlegm-damp constitution was the highest.The gender,age,height,weight and BMI had significant correlation with the TCM constitution(P＜0.05).The fat content,fat vol-ume,muscle volume,area of transverse section ROI(AROI),transverse diameter,anteroposterior diameter and scan length/transverse diameter had significant correlation with the TCM constitution(P＜0.05).The differ-ences in BMI and fat content had statistical difference among the phlegm-damp constitution,Qi-stagnation constitution and the other Chinese medicine constitutions(P＜0.01).The fat content,fat volume and muscle volume had significant correlation with BMI(P＜0.01).The muscle content had no significant correlation with BMI(P＞0.05).The muscle content,scan length and transverse diameter/anteroposterior diameter had no significant correlation with the TCM constitution(P＞0.05).Conclusion The distribution difference of TCM constitution in adult persons with different BMI has the statistical significance.The chest CT quantita-tive parameters are closely correlated with TCM constitution classification.

OBJECTIVES: Bladder cancer is a common malignancy with high incidence and poor prognosis. N⁶-methyladenosine (m⁶A) modification is widely involved in diverse physiological processes, among which the m⁶A recognition protein YTH N⁶-methyladenosine RNA binding protein F2 (YTHDF2) plays a crucial role in bladder cancer progression. This study aims to elucidate the molecular mechanism by which O-linked N-acetylglucosamine (O-GlcNAc) modification of YTHDF2 regulates its downstream target, period circadian regulator 1 (PER1), thereby promoting bladder cancer cell proliferation. METHODS: Expression of YTHDF2 in bladder cancer was predicted using The Cancer Genome Atlas (TCGA). Twenty paired bladder cancer and adjacent normal tissues were collected at the clinical level. Normal bladder epithelial cells (SV-HUC-1) and bladder cancer cell lines (T24, 5637, EJ-1, SW780, BIU-87) were examined by quantitative real-time PCR (RT-qPCR), Western blotting, and immunohistochemistry for expression of YTHDF2, PER1, and proliferation-related proteins [proliferating cell nuclear antigen (PCNA), minichromosome maintenance complex component 2 (MCM2), Cyclin D1]. YTHDF2 was silenced in 5637 and SW780 cells, and cell proliferation was assessed by Cell Counting Kit-8 (CCK-8), colony formation, and EdU assays. Bioinformatics was used to predict glycosylation sites of YTHDF2, and immunoprecipitation (IP) was performed to detect O-GlcNAc modification levels of YTHDF2 in tissues and cells. Bladder cancer cells were treated with DMSO, OSMI-1 (O-GlcNAc inhibitor), or Thiamet G (O-GlcNAc activator), followed by cycloheximide (CHX), to assess YTHDF2 ubiquitination by IP. YTHDF2 knockdown and Thiamet G treatment were further used to evaluate PER1 mRNA stability, PER1 m⁶A modification, and cell proliferation. TCGA was used to predict PER1 expression in tissues; SRAMP predicted potential PER1 m⁶A sites. Methylated RNA immunoprecipitation (MeRIP) assays measured PER1 m⁶A modification. Finally, the effects of knocking down YTHDF2 and PER1 on 5637 and SW780 cell proliferation were assessed. RESULTS: YTHDF2 expression was significantly upregulated in bladder cancer tissues compared with adjacent tissues (mRNA: 2.5-fold; protein: 2-fold), which O-GlcNAc modification levels increased 3.5-fold (P<0.001). YTHDF2 was upregulated in bladder cancer cell lines, and its knockdown suppressed cell viability (P<0.001), downregulated PCNA, MCM2, and CyclinD1 (all P<0.05), reduced colony numbers 3-fold (P<0.01), and inhibited proliferation. YTHDF2 exhibited elevated O-GlcNAc modification in cancer cells. OSMI-1 reduced YTHDF2 protein stability (P<0.01) and enhanced ubiquitination, while Thiamet G exerted opposite effects (P<0.001). Thiamet G reversed the proliferation-suppressive effects of YTHDF2 knockdown, promoting cell proliferation (P<0.01) and upregulating PCNA, MCM2, and CyclinD1 (all P<0.05). Mechanistically, YTHDF2 targeted PER1 via m⁶A recognition, promoting PER1 mRNA degradation. Rescue experiments showed that PER1 knockdown reversed the inhibitory effect of YTHDF2 knockdown on cell proliferation, upregulated PCNA, MCM2, and Cyclin D1 (all P<0.05), and promoted bladder cancer cell proliferation (P<0.001). CONCLUSIONS O-GlcNAc modification YTHDF2 promotes bladder cancer development by downregulating the tumor suppressor gene PER1 through m⁶A-mediated post-transcriptional regulation.
Humans ; Urinary Bladder Neoplasms/metabolism* ; RNA-Binding Proteins/genetics* ; Cell Proliferation ; Cell Line, Tumor ; Disease Progression ; Acetylglucosamine/metabolism* ; Adenosine/metabolism* ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor

OBJECTIVE: To explore the effectiveness of arthroscopic release of elbow joint assisted by medial small incision ulnar nerve release in the treatment of non-traumatic elbow stiffness. METHODS: The clinical data of 15 patients with non-traumatic elbow stiffness treated with arthroscopic release of elbow joint assisted by medial small incision ulnar nerve release between April 2019 and September 2023 were retrospectively analyzed. There were 6 males and 9 females with an average age of 46 years ranging from 34 to 56 years. The causes included rheumatoid arthritis in 3 cases, gouty arthritis in 2 cases, loose bodies in 3 cases, and elbow osteoarthritis in 7 cases. There were 4 cases with ulnar neuritis and 3 cases with synovial osteochondromatosis. The duration of elbow stiffness ranged from 6 to 18 months, with an average of 10 months. The operation time and intraoperative blood loss were recorded. The effectiveness was evaluated by visual analogue scale (VAS) score, range of elbow motion (maximum flexion, maximum extension, and total flexion and extension), Mayo score, and Hospital for Special Surgery (HSS) elbow score. RESULTS: The operation time was 60-90 minutes, with an average of 65 minutes, and the intraoperative blood loss was 40-100 mL, with an average of 62 mL. All patients were followed up 13-18 months, with an average of 14 months. There was no complication such as vascular and nerve injury, poor wound healing, collateral ligament injury, elbow joint space narrowing, osteophyte proliferation, or loose body formation around the joint. At last follow-up, the elbow range of motion (maximum flexion, maximum extension, and total flexion and extension), VAS score, and Mayo score significantly improved when compared with those before operation ( P<0.05). The HSS elbow score was 85-95, with an average of 92; 12 cases were excellent, 3 cases were good, and the excellent and good rate was 100%. CONCLUSION Arthroscopic release of elbow joint assisted by medial small incision ulnar nerve release is an effective way to treat non-traumatic elbow stiffness, which has the advantages of small trauma, short operation time, and good effectiveness. It can carry out early elbow rehabilitation training and significantly improve elbow function.
Humans ; Male ; Female ; Arthroscopy/methods* ; Adult ; Middle Aged ; Elbow Joint/physiopathology* ; Retrospective Studies ; Range of Motion, Articular ; Treatment Outcome ; Ulnar Nerve/surgery* ; Operative Time

Objective To evaluate the effectiveness of bronchial artery embolization(BAE)combined with surgical lobectomy in treating patients with refractory hemoptysis caused by bronchiectasis.Methods The clinical data of 168 patients with bronchiectasis and refractory hemoptysis,who were treated at the Wuhan Jinyintan Hospital of China from January 2018 to January 2022,were retrospectively analyzed.Of the 168 patients,91 underwent lobectomy(control group),and 71 underwent BAE combined with lobectomy(observation group).The therapeutic efficacy,intraoperative blood loss,surgical operation time,postoperative 3-day drainage volume,length of hospital stay,hemoptysis recurrence rate,and complications were compared between the two groups.Results In the observation group,the clinical efficacy was higher than that in the control group,while the intraoperative blood loss,operation time,length of hospital stay,postoperative 3-day drainage volume and recurrence rate were lower than those in the control group(all P＜0.05).No statistically significant difference in the incidence of complications existed between the two groups(P＞0.05).Conclusion In treating patients with refractory hemoptysis due to bronchiectasis,BAE combined with lobectomy can improve the therapeutic efficacy while not increasing the risk of complications.

With the advancement of education,teaching methods have been continuously improved and optimized to en-hance students'learning experiences.In teaching the course of pathophysiology,a core discipline for medical students,integra-tion of Case-Based Learning(CBL)with the flipped classroom model can serve as a powerful pedagogical tool by stimulating students'interest,promoting collaborative learning,enhancing teacher-student interaction,and fostering a more active and en-gaging classroom environment.It also equips students with the confidence to better address real-world medical scenarios.This pa-per examines the application effect of the integrated teaching method on the teaching of pathophysiology and evaluates its pedagog-ical effectiveness.

Osteosarcoma(OS)is a common primary malignant bone tumor with high mortality,disability,metastasis,and recurrence rates and a complex pathogenesis,Resulting in serious effects on patient quality of life and huge economic burdens on families and society.Traditional Chinese medicine(TCM)has"multi-target,multi-component and multi-pathway"characteristics.Recent studies using animal and cell models demonstrated that the mechanism of OS progression was related to Notch,mitogen-activated protein kinase,Wnt/β-catenin,phosphatidylinositol 3-kinase/AKT,Hedgehog and nuclear factor-κB,transforming growth factor-β/Smad and signal transducer and activator of transcription pathways.TCM can exert anti-tumor effects by influencing biological processes such as cell proliferation,migration,invasion,apoptosis,and autophagy via interfering with the above signaling pathways.This review considers the roles of these signaling pathways in OS and summarizes the current research status of TCM interventions in the prevention and treatment of OS,with the aim of providing a reference for future studies of TCM treatments of OS and to provide new ideas for its clinical treatment.

Objective To observe the effectiveness and safety of DiaSphere embolized microsphere TACE for treating primary hepatocellular carcinoma(HCC).Methods Totally 188 patients with HCC were prospectively enrolled and randomly assigned to research group(n=93)and control group(n=95),who underwent TACE with DiaSphere embolized microspheres and Embosphere embolized microspheres,respectively.The incidence of TACE-related adverse events were recorded.The therapeutic efficacy 1 month after the first TACE,also 1 and 3 months after the last TACE,and liver functions 1 month after the first and last TACE were compared between groups.Results In research group,there were 69 cases underwent 1 time TACE,22 cases underwent 2 times and 2 cases underwent 3 times TACE,while in control group,there were 82 cases underwent 1 time and 13 cases underwent 2 times TACE,respectively.No statistical difference of the incidence of adverse events was found between groups(77.42%[72/93]vs.76.84%[73/95],P=1.000).One month after the first TACE,7 cases in research group and 11 cases in control group were lost to follow-up,respectively.One month after the last TACE,12 cases were lost to follow-up in both groups,and 3 months after the last TACE,28 cases were lost to follow-up in both groups.No significant difference of objective response rate nor disease control rate was found between groups at the above time points(all P＞0.05).One month after the first and last TACE,liver function indicators were not different between groups(all P＞0.05).Conclusion Both the short-term efficacy and safety of TACE with DiaSphere embolized microspheres for treating HCC were good.

Objective:To study the risk factors for acute kidney injury (AKI) following one-stage revision surgery combined with intra-articular antibiotics infusion for periprosthetic joint infection (PJI) of the hip joint.Methods:A retrospective analysis was conducted on the data of 168 patients with hip PJI who underwent one-stage revision surgery combined with intra-articular antibiotics infusion in the Department of Joint Surgery, the First Affiliated Hospital of Xinjiang Medical University, from May 1, 2010 to April 30, 2024. There were 87 males and 81 females with an average age of 60.1±14.6 years (range: 21-89 years). The body mass index (BMI) was 24.9±4.6 kg/m 2 (range: 17-41 kg/m 2). PJI was diagnosed according to the criteria of Musculoskeletal Infection Society (MSIS) in 2011. AKI was diagnosed and classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. For AKI group and non-AKI group, risk factors were screened by univariate analysis on their age, gender, BMI, BMI≥30 kg/m 2 (yes/no), American Society of Anesthesiologists (ASA) score (II/III), hypertension, diabetes, chronic kidney disease (CKD), surgical side (left/right), duration of intravenous antibiotic use, duration of intra-articular antibiotic use, preoperative blood transfusion, postoperative blood transfusion, baseline hemoglobin value, anemia grade (none/mild/moderate), baseline serum creatinine value, baseline serum creatinine grade (normal/below normal range/above normal range). Variables with P<0.10 were included in the multivariate logistic regression model to identify independent risk factors. Results:The overall incidence of AKI was 9.52%(16/168), among which 50%(8 cases) were stage I AKI, transient and requiring no special treatment. 12.5% (2 cases) were stage II AKI and did not undergo dialysis. 37.5%(6 cases) were stage III AKI. One case needed temporary hemodialysis, and there was no patient requiring long-term dialysis. There were significant differences in age, diabetes, chronic kidney disease and ASA score between AKI group and non-AKI group ( P<0.05). The univariate logistic regression analysis revealed that there were significant differences in age ( P=0.005), BMI ( P=0.078), ASA score level Ⅲ ( P=0.037), diabetes ( P=0.025), CKD ( P=0.003), and low baseline serum creatinine level ( P=0.056). Multivariate logistic regression analysis showed that age, CKD and low baseline serum creatinine level were independent risk factors for AKI ( P<0.05). Conclusions:The incidence of AKI after one-stage revision surgery combined with local antibiotic use in the joint cavity was relatively low in the treatment of PJI after total hip arthroplasty. Hower elderly patients with a history of CKD, or a low baseline serum creatinine level before surgery were at higher risk of developing AKI.