OBJECTIVES: To investigate the role of activating transcription factor 3 (ATF3) in atherosclerotic plaques for regulating inflammatory responses during atherosclerosis (AS) progression. METHODS: Human coronary artery specimens from autopsy cases were examined for ATF3 protein expression and localization using immunofluorescence staining and Western blotting. Apolipoprotein E-deficient (ApoE^-/-) mouse models of AS induced by high-fat diet (HFD) feeding for 12 weeks were subjected to tail vein injection of adeno-associated virus serotype 9 (AAV9) to knock down ATF3 expression. After an additional 5 weeks of HFD feeding, the mice were euthanized for analyzing structural changes of the aortic plaques, and the expression levels of ATF3, inflammatory factors (CD45, CD68, IL-1β, and TNF-α), and NF-κB pathway proteins (P-IKKα/β and P-NF-κB p65) were detected. In the cell experiment, THP-1-derived foam cells were transfected with an ATF3-overexpressing plasmid or an ATF3-specific siRNA to validate the relationship between ATF3 and NF‑κB signaling. RESULTS: In human atherosclerotic plaques, ATF3 expression was significantly elevated and partially co-localized with CD68. ATF3 knockout in ApoE^-/- mice significantly increased aortic plaque volume, upregulated the inflammatory factors, enhanced phosphorylation of the NF‑κB pathway proteins, and increased the expressions of VCAM1, MMP9, and MMP2 in the plaques. In THP-1-derived foam cells, ATF3 silencing caused activation of the NF‑κB pathway, while ATF3 overexpression suppressed the activity of the NF-κB pathway. CONCLUSIONS AS promotes ATF3 expression, and ATF3 deficiency exacerbates AS progression by enhancing plaque inflammation via activating the NF-κB pathway, suggesting the potential of ATF3 as a therapeutic target for AS.
Animals ; Activating Transcription Factor 3/metabolism* ; Signal Transduction ; NF-kappa B/metabolism* ; Humans ; Mice ; Plaque, Atherosclerotic/metabolism* ; Inflammation/metabolism* ; Apolipoproteins E ; Atherosclerosis/metabolism* ; Diet, High-Fat

Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects，so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method：sham operation group (sham)，2-week nerve transection group (NB-2W)，6-week nerve transection group (NB-6W)，2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W)，with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling，while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased，while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group，but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group，but higher than that in the sham group (P<0.05).Compared with the sham group，the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group，NB-P-2W group had lower bladder leakage point pressure (BLPP)，but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group，NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that，with the extension of nerve transection time，bladder fibrosis gradually worsened，the bladder wall became rough and thickened，calculi were visible inside，and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups，and no hydronephrosis was observed in the upper urinary tract.In addition，Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos，Collagen Ⅰ and α-SMA than the sham group (P<0.01)，while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis，but its mechanism needs further study.

Objective: To investigate the influencing factors of overactive bladder (OAB) in college freshmen and the impacts of OAB on their mental health, quality of life and social interaction. Methods: An epidemiological questionnaire survey was conducted in an anonymous manner on the prevalence of OAB among 5300 freshmen aged 17 to 22 years enrolled in the 2023—2024 academic year in Xinxiang Medical University and Sanquan College of Xinxiang Medical University.The questionnaire included questions on basic information, history of urinary tract infection, constipation, smoking, history of alcohol consumption, history of coffee/strong tea drinking, history of carbonated beverage drinking, redundant prepuce, phimosis, holding urine, chronic insomnia, self-rating anxiety scale (SAS), quality of life score (QoL), and social avoidance and distress scale (SADS).The influencing factors of OAB were analyzed with multivariate logistic regression analysis.The subjects were grouped according to whether they had OAB, and the differences in SAS, QoL and SADS between the OAB group and non-OAB group were compared.The impacts of OAB on the anxiety level, quality of life, and social interaction were analyzed with multiple linear regression analysis. Results: The overall prevalence rate of OAB was 4.9% (244/5018).Multivariate logistic regression analysis showed that the history of urinary tract infection (OR=0.177), constipation (OR=0.636), smoking (OR=0.582), alcohol consumption (OR=0.685), coffee/strong tea drinking (OR=0.387), carbonated beverage drinking (OR=0.631), redundant prepuce (OR=0.673), phimosis (OR=0.311), urine holding (OR=0.593), and chronic insomnia (OR=0.256) were influencing factors for the occurrence of OAB (P＜0.05).The OAB group had higher SAS score [(41.18±6.54) vs. (38.61±6.36)], QoL score [(3.65±1.20) vs. (2.79±0.95)], social avoidance score [(6.25±1.86) vs. (5.86±1.51)], social distress score [(6.27±1.59) vs. (5.97±1.32)], and total SADS score [(12.51±2.35) vs. (11.84±2.01)] than the non-OAB group (P＜0.05).The results of multiple linear regression analysis showed that OAB could independently affect the scores of QoL, SAS, and SADS.The OAB group had higher scores of QoL, SAS, and SADS compared with the non-OAB group (P＜0.001). Conclusion: History of urinary tract infection, constipation, smoking, alcohol consumption, coffee/strong tea drinking, carbonated beverage drinking, redundant prepuce, phimosis, urine holding, and chronic insomnia are influencing factors for the occurrence of OAB in male college students.Moreover, OAB has negative impacts on their mental health, quality of life, and social interaction.

Skeletal system and immune system are 2 important systems for maintaining human life.Osteoporosis is a complex pathological change of bone tissue.Immune system disorders have become the cause of osteoporosis through affecting the proliferation and differentiation of osteoblasts and osteoclasts.Innate immunity,adaptive immunity,and cytokines play crucial roles in bone resorption and remodeling by regulating the signaling pathways of osteoblasts and osteoclasts.Therefore,immunoporosis has emerged for studying the inseparable relationship between osteoporosis and immune system.This article reviews the research progresses on immunoporosis,aiming to provide references for immunotherapy of osteoporosis.

Objective To investigate the effects of Jiuwei Jianbu Drink on oxidative stress and inflammatory injury in rats with knee osteoarthritis via the high mobility group box-1 protein(HMGB1)/receptor for advanced glycation endproducts(RAGE)/phosphatidyli-nositol 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods A total of 60 rats were randomly divided into six groups according to the random number table method:blank control group,model group,positive drug group,and Jiuwei Jianbu Drink low-,medium-,and high-dose groups,with 10 rats in each group.Except for the blank control group,knee osteoarthritis models were estab-lished in the other groups,which were then subjected to corresponding treatments.Knee joint diameter and mechanical pain and thermal pain threshold changes were observed.Hematoxylin-eosin staining and safranin O/fast green staining were used to assess pathological changes in cartilage tissue.Oxidative stress markers and inflammatory factor levels in knee joint cartilage tissue of each group were meas-ured.Western blot was used to detect the expression of proteins related to the HMGB1/RAGE/PI3 K/Akt signaling pathway in knee joint tissues.Results Compared with the blank control group,the model group exhibited increased knee joint diameter and decreased mechan-ical pain and thermal pain threshold.Jiuwei Jianbu Drink at all doses groups and the positive control group significantly improved these in-dicators in a dose-dependent manner(P＜0.05).Additionally,the Mankin score and Osteoarthritis Research Society International(OARSI)score in the model group were significantly higher than those in the blank control group,while Jiuwei Jianbu Drink intervention significantly reduced the OARSI score,with the best effect observed in the high-dose group(P＜0.05).Compared with the blank con-trol group,the model group showed increased levels of nitric oxide(NO)and malondialdehyde(MDA),decreased levels of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px),and significantly elevated levels of tumor necrosis factor-alpha(TNF-α)and interleukin-1β(IL-1β).Compared with the model group,Jiuwei Jianbu Drink significantly inhibited oxidative stress and inflam-matory responses,especially at high doses(P＜0.05).Moreover,the expression of HMGB1,RAGE,p-PI3K/PI3K,and p-Akt/Akt in the model group was higher than that in the blank control group,while Jiuwei Jianbu Drink intervention dose-dependently downregulat-ed the expression of these proteins(P＜0.05).Conclusion Jiuwei Jianbu Drink alleviates oxidative stress and inflammatory injury in rats with knee osteoarthritis by inhibiting the HMGB1/RAGE/PI3K/Akt signaling pathway,thereby improving cartilage pathological chan-ges and demonstrating potential therapeutic value.

Objective:Through imaging analysis, the association between the degree of paravertebral muscle fat infiltration (fat infiltration, FI), trabecular bone score (TBS) and the fracture risk of postmenopausal osteoporosis (OP) patients was explored.Methods:A retrospective selection was made of 110 postmenopausal female patients diagnosed with OP at Jiangnan Hospital Affiliated to Zhejiang Chinese Medical University from Mar. 2023 to Mar. 2024. Additionally, healthy postmenopausal individuals who underwent physical examinations during the same period were included in the healthy postmenopausal group. The levels of paravertebral muscle FI and TBS in the two groups were compared. Postmenopausal patients with OP were followed up for one year, and the incidence of fractures in the patients was analyzed by Kaplan-Meier curve. The patients were divided into the fracture group ( n=29) and the non-fracture group ( n=81). The clinical data of the two groups of patients at admission were compared. Binary Logistic regression was used to analyze the independent risk factors for fractures in patients. Spearman was used to analyze the correlation of fracture risk within one year among FI, TBS and postmenopausal OP patients. ROC was used to evaluate the predictive value of each independent risk factor. Results:The proportion of severe paraverteal muscle FI in the postmenopausal OP group was significantly higher than that in the healthy physical examination group (multifisis FI, erector spinae FI, psoas major muscle FI, χ2=14.96, 17.17, 16.08, all P=0.00), and the lumbar TBS level was significantly lower (t=4.52, P=0.00). The Kaplan-Meier curve indicated that the degree of paravertebral muscle FI affected the incidence of fractures in patients ( χ2=14.58, P=0.00), and the level of lumbar TBS also affected the incidence of fractures in patients ( χ2=6.02, P=0.01). The bone mineral density (BMD), cross-sectional area of the multifidus muscle (CSA), erectus spinae muscle area (CSA), and psoas major muscle area (CSA) of patients in the fracture group were significantly lower than those in the non-fracture group ( t=10.72, 3.40, 3.46, 2.12). P=0.00, 0.00, 0.00, 0.04), while the indicators of TNF-α, IL-6 and PCT were higher than those in the non-fracture group ( t=4.11, 4.96, 5.48, all P=0.00). Binary Logistic regression analysis showed that high-level BMD ( OR=0.52, 95%CI: 0.27-0.77, P=0.01) and TBS ( OR=0.68, 95 %CI: 0.48-0.93 ,P=0.02) were protective factors for fractures in postmenopausal patients with OP. Multifidus FI ( OR=1.73, 95 %CI: 1.48-1.98, P=0.03), erector spinae FI ( OR=1.25, 95%CI:1.10-1.50, P=0.01), and psoas major FI ( OR=1.96, 95 %CI: 1.71-2.21, P=0.03) is the risk factor. Spearman analysis indicated that the paravertebral muscle FI of patients at the first diagnosis of OP was positively correlated with the risk of fracture within one year after diagnosis ( r=0.88, 0.91, 0.82, P=0.01, 0.01, 0.02), while the BMD and TBS values were negatively correlated ( r=-0.92, -0.77, P=0.00, 0.02). ROC showed that the values of multifidus FI, erector spinae FI, psoas major FI, BMD and TBS at admission all had good predictive efficacy for fractures within one year in patients [area under the ROC curve (AUC) =0.88, 0.84, 0.86, 0.73, 0.82]. Moreover, the predictive efficiency of the joint model is higher (AUC=0.89) . Conclusions:Higher BMD and TBS levels protect against fractures in postmenopausal OP patients ( OR=0.523-0.675), while severe paraspinal muscle FI (multifidus: OR=1.726; erector spinae: OR=1.248; psoas: OR=1.961) increases risk. The combined model shows excellent predictive value (AUC=0.890), serving as effective clinical warning indicators for fracture risk assessment.

Cardiovascular disease(CVD)is currently one of the most severe diseases endangering human health,encompassing myocardial ischemia syndrome,myocardial fibrosis,atrial fibrillation,and other conditions.MicroRNAs(miRNAs/miR)are a class of small non-coding RNAs that can bind to specific se-quences and subsequently regulate post-transcriptional processing,translation,or epigenetic modifications,thereby modulating gene expression.Studies have found that miR-223 is associated with the occurrence and de-velopment of CVD and represents a potential specific therapeutic target.This article summarizes the relevant re-search on miR-223 in CVD,focusing on myocardial ischemia syndrome,myocardial fibrosis,and atrial fibrilla-tion,and discusses its application prospects and challenges as a specific therapeutic target,providing new ideas for the diagnosis and treatment of CVD.

AIM:To observe the effect and mech-anism of cuttlebone extract regulating vascular en-dothelial growth factor(VEGF)/phosphatidylinosi-tol 3-kinase(PI3K)/protein kinase B(AKT)pathway on refractory wounds in rats.METHODS:Cuttle-bone extract(CE)was obtained by water extraction of cuttlebone.Fifty SD rats were randomly divided into negative Control group,Model group,Cuttle-bone extract low-dose(CE(L))group,Cuttlebone extract high-dose(CE(H))group,and cuttlebone ex-tract high-dose+inhibitor(CE(H)+LY294002)group.After the refractory wound model was successfully established,0.02％furacillin solution or cuttlebone extract solution were applied to the wound area of rats in each group,and the treatment was adminis-tered once a day.After 14 days of treatment for re-fractory wounds,the changes in wound healing,angiogenesis,inflammation and expression of relat-ed regulatory proteins were quantitatively ana-lyzed by measuring skin ulcer wound area,patho-logical sections,immunofluorescence staining,Eli-sa,Western blot,RT-qPCR and other methods.RE-SULTS:Compared with Model group,CE(L)and CE(H)groups can increase the number of epithelial cells and collagen,and promote the healing of re-fractory wound in rats.Serum VEGF,skin tissue mi-crovascular density,P-PI3K,P-AKT,VEGF protein ex-pression and mRNA expression levels of PI3K,Akt,VEGF and eNOS were increased(P＜0.05),while se-rum TNF-α and IL-6 levels were decreased(P＜0.05).LY294002 could partially reverse the repair-ing effect of high dose cuttlebone extract on refrac-tory wound(P＜0.05).CONCLUSION:Cuttlebone ex-tract can regulate the VEGF/PI3K/AKT signaling pathway,inhibit the inflammatory response of re-fractory wounds in rats,induce angiogenesis and promote wound healing.

Objective:To investigate the effect of left colonic artery (LCA) preservation on rectal cancer patients' short-term postoperative anal function and quality of life.Methods:Two-hundred ninty-two patients with rectal cancer at the Department of Gastrointestinal Surgery of Peking University First Hospital between Jan 2022 and Dec 2023 were enrolled . The patients were divided into two groups according to whether the LCA was preserved during surgery or not. The LARS scale and EORTC QLQ-CR29 quality of life questionnaire were used to assess postoperative anal function and quality of life.Results:There were no significant differences between the two groups in terms of the amount of surgical blood loss and the number of lymph node dissections in the root No. 253 group and the time to postoperative voiding (all P>0.05). However, the LARS scores at 1 and 3 months postoperatively were significantly lower in the preserved LCA group than in the LCA nonpreserved group, especially for gas incontinence, loose stool leakage, and number of bowel movements (all P<0.05). The EORTC QLQ-CR29 scores showed that the LCA preserved group recovered significantly better than the non-preserved group in terms of postoperative voiding dysfunction ( P=0.007), urinary incontinence ( P=0.006), mucus discharge ( P=0.009), and fecal incontinence symptoms ( P<0.001). Male sexual dysfunction recovery was quicker in the preserved LCA group ( P=0.043), but there was no significant difference between the two groups at 3 months postoperatively( P>0.05). Conclusion:Preservation of the left colonic artery in low anterior resection of rectal cancer helps to reduce the incidence of postoperative low anterior resection syndrome, improve genitourinary symptoms, and improve patients' quality of life.

Objective:Analyze the risk factors of gastrointestinal perforation caused by foreign body and summarize the experience of surgical treatment of foreign bodies.Method:From Jan 2008 to Dec 2023, 89 patients with foreign bodies in the digestive tract were admitted to the Department of Gastrointestinal Surgery, Peking University First Hospital. Relevant data were collected and binary logistic regression was used to analyze the independent risk factors for intestinal perforation, resection and anastomosis of intestine or enterostomy/colostomy.Results:The mean age of 89 patients was (60.1±16.2) years old, 65 patients (73%) had unintentionally ingested foreign bodies. The most common foreign bodies were jujube pits (40 cases). Thirty-nine patients diagnosed with gastrointestinal perforation. Binary Logistic regression analysis showed that the total number of leukocytes ( OR=4.085, 95% CI: 1.214-13.745, P=0.023), sharp foreign body ( OR=26.124, 95% CI: 5.194-131.392, P<0.001), and the location of foreign body ( OR=3.980, 95% CI: 1.178-13.465, P=0.026) were the independent risk factors for gastrointestinal perforation. Thirty-three patients underwent gastrointestinal repair surgery, and 36 patients underwent resection and anastomosis of intestine or enterostomy/colostomy. Binary Logistic regression analysis showed that the foreign body located in the colorectum ( OR=71.928, 95% CI: 4.646-1 113.479, P=0.002) and the length of the foreign body ≤2.5 cm ( OR=5.791, 95% CI: 1.606-20.882, P=0.007) were the independent risk factors for resection and anastomosis of intestine or enterostomy/colostomy. Conclusions:Leukocyte count ≥10×10 9/L, sharp foreign body, and location of foreign body are independent risk factors for gastrointestinal perforation. Foreign body located in the colorectum and foreign body length ≤2.5 cm are risk factors for resection and anastomosis of intestine or enterostomy/colostomy.