Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

Over the past 40 years,gynecological ultrasound in China has evolved from two-dimensional imaging to multi-modal imaging,quantitative analysis,artificial intelligence analysis and minimally invasive treatment,playing more and more important role in diagnosis and treatment of gynecological diseases.The development of diagnostic and therapeutic gynecological ultrasound techniques and relative clinical application advances in China were reviewed,and the future development prospects were looked forward to in this article.

Objective:To develop a quality control model for anal sphincter ultrasound images and validate its diagnostic performance across multiple centers.Methods:A retrospective analysis was conducted on anal sphincter ultrasound images from seven medical centers in China between May 2019 and June 2022. A total of 7 040 images from 3 116 patients were included and divided into a training set（4 912 images）and a validation set（2 128 images）. The images were classified as standard or non-standard images by three experts. Three models were developed based on different image feature extraction methods：a single-branch model，a multi-branch weighted model，and a multi-branch ensemble model. The diagnostic performance of each model was evaluated using the area under the ROC curve（AUC），sensitivity，specificity，accuracy，positive predictive value，and negative predictive value，respectively. The optimal model was selected and compared with the performance of 4 doctors with varying experience levels. Sixty days later，the images with the assistance of the model's output were reassessed by the doctors to evaluate its impact on manual quality control.Results:① Among the 3 models，the multi-branch ensemble model demonstrated the highest AUC and sensitivity，with an AUC of 0.966（95% CI=0.958 - 0.974），a sensitivity of 91.83%，and a specificity of 91.41%. This model was named M quality. ② M quality's AUC was slightly lower than that of Senior A and B（0.966 vs. 0.976，0.976，and P<0.05），its sensitivity was slightly lower than that of Senior A（91.83% vs. 95.61%， P<0.001）but comparable to Senior B（91.83% vs. 92.89%， P=0.315），its specificity was slightly lower than Senior A and B（91.41% vs. 94.44%，98.18%，and P<0.05）. However，M quality significantly outperformed Junior A and B in AUC and sensitivity（AUC：0.966 vs. 0.850，0.818；sensitivity：91.83% vs. 84.90%，61.46%；all P<0.001），its specificity was higher than that of Junior A（91.41% vs. 80.28%， P<0.001）but lower than that of Junior B（91.41% vs. 95.96%， P<0.001）. ③ With model assistance，Senior B's sensitivity（92.89% vs. 94.20%， P=0.001）and Senior A's specificity（94.44% vs. 96.56%， P<0.001）improved significantly. Junior A and B showed significant improvements in AUC and sensitivity（AUC：0.931 vs. 0.850，0.914 vs. 0.818；sensitivity：91.83% vs. 84.90%，89.53% vs. 61.46%；all P<0.001）. After model assistance，Junior A's specificity increased（93.62% vs. 80.28%， P<0.001），while Junior B's specificity decreased（91.60% vs. 95.96%， P=0.013）. Conclusions:This study develops a quality control model for anal sphincter ultrasound images with robust diagnostic performance，approaching the level of seniors. The model significantly enhances the image quality assessment capabilities of juniors，demonstrating promising clinical application potential.

Objective: To investigate whether TYRO protein tyrosine kinase-binding protein (TYROBP) affects the progression of diabetic kidney disease (DKD) through the extracellular signal-regulated kinase ( ERK) pathway. Methods: Key genes in DKD were identified through bioinformatics analysis . Immunohistochemical staining and quantitative real-time PCR (qPCR) were used to validate the expression levels of TYROBP in a DKD mouse model and high glucose-stimulated NRK-52E cells . NRK-52E cell models with stable TYROBP overexpression/knockdown and their corresponding empty vector (ev) /scrambled sequence (ss) controls were established via lentiviral trans- fection . Cells were treated with 5 . 5 mmol/L or 30. 0 mmol/L glucose for 72 hours to mimic normal glucose (NG) and high glucose ( HG) conditions , respectively. High glucose medium containing 3 . 5 μmol/L FR180204 was used for ERK inhibitor intervention . The experiment included seven groups : ev + NG , ev + HG , oe-TYROBP + HG , ss + NG , ss + HG , sh-TYROBP + HG , and sh-TYROBP + HG + ERK inhibitor. Western blot was used to de- tect the expression levels of phosphorylated ERK/total ERK (p-ERK/ERK) , apoptosis-related proteins B-cell lym- phoma-2 (Bcl-2) and Bcl-2-associated X protein ( Bax) , and epithelial-mesenchymal transition ( EMT)-related proteins E-cadherin and α-smooth muscle actin ( α-SMA) . Tetramethylrhodamine ethyl ester (TMRE) staining and Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) flow cytometry were performed to as- sess mitochondrial membrane potential and apoptosis levels . Results: Bioinformatics analysis identified TYROBP as a key gene in DKD . In vivo and in vitro validation showed increased TYROBP mRNA levels in DKD models . The results from the HG model indicated that , compared to the ev + NG/ss + NG group , the ev + HG/ss + HG group demonstrated increased p-ERK/ERK expression , reduced mitochondrial membrane potential , elevated apoptosis , and enhanced EMT. In TYROBP-perturbed NRK-52E cells , compared to the ev + HG group , the oe-TYROBP + HG group showed decreased p-ERK/ERK expression (P < 0. 01) , increased mitochondrial membrane potential (P < 0. 05) , reduced apoptosis (P < 0. 001) , and attenuated EMT; whereas compared to the ss + HG group , the sh- TYROBP + HG group exhibited increased p-ERK/ERK expression ( P < 0. 001) , decreased mitochondrial mem- brane potential (P < 0. 01) , elevated apoptosis (P < 0. 001) , and enhanced EMT. Furthermore , compared to the sh-TYROBP + HG group , the sh-TYROBP + HG + ERK inhibitor group displayed reduced p-ERK/ERK expression (P < 0. 01) , increased mitochondrial membrane potential ( P < 0. 001) , decreased apoptosis ( P < 0. 001) , and suppressed EMT. Compared with the scrambled sequence control + high glucose group , the TYROBP knockdown + high glucose group showed elevated p-ERK/ERK expression ( P < 0. 001) , reduced mitochondrial membrane potential (P < 0. 01) , increased apoptosis level (P < 0. 001) , and enhanced EMT. Compared with the TYROBP knockdown + high glucose group , the TYROBP knockdown + high glucose + ERK inhibitor group demonstrated decreased p-ERK/ERK expression (P < 0. 01) , restored mitochondrial membrane potential (P < 0. 001) , reduced apoptosis level (P < 0. 001) , and suppressed EMT. Conclusion TYROBP may regulate the ERK signaling path- way to modulate apoptosis- and EMT-related proteins , thereby influencing mitochondrial membrane potential , apop- tosis , and EMT in renal tubular epithelial cells and contributing to DKD progression .

AIM:This study aims to investigate the effects of Jiedu-Shengji ointment(JDSJG)on wound healing in diabetic rats by modulating the protein kinase R-like endoplasmic reticulum kinase(PERK)/inositol-requiring enzyme 1(IRE1)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway in the context of endoplasmic reticulum stress(ERS).METHODS:Male Sprague-Dawley rats were randomly assigned to four groups:control group,model group,detoxification muscle ointment group,and sulfadiazine silver cream group.All groups,except the control,were administered an intraperitoneal injection of 45 mg/kg streptozotocin to induce diabetes.The control and model groups received daily applications of normal saline,while the detoxification myogen ointment and sulfadiazine silver cream groups received their respective treatments daily.After dressing changes,wounds were bandaged with sterile gauze.Following 14 d of continuous treatment,wound healing was assessed and healing rates calculated.Histopathologi-cal changes in wound tissues were analyzed using HE staining.Transmission electron microscopy was utilized to observe the number,morphology,and swelling of endoplasmic reticulum in the wound tissues.The expression and distribution of PERK,IRE1 and thioredoxin interacting protein(TXNIP)was assessed by immunohistochemistry,while Western blot was used to measure the levels of apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),TXNIP and NLRP3.ELISA was conducted to quantify the inflammatory cytokines interleukin-18(IL-18)and IL-1β.RE-SULTS:After 14 d of intervention,significant differences were observed in wound tissue parameters across the groups.The model group exhibited a significantly lower wound healing rate compared to the control group(P<0.01),with in-creased wound exudation,poor granulation tissue growth,and elevated the protein levels of PERK,IRE1,TXNIP,CHOP,NLRP3 and ASC(P<0.01),as well as significantly higher levels of IL-1β and IL-18(P<0.01).In contrast,the detoxification muscle ointment group showed a marked improvement in wound healing rate(P<0.01),reduced inflamma-tory exudation,improved granulation tissue growth,and significant decreases in TXNIP expression(P<0.01),along with lower levels of PERK,IRE1,CHOP,ASC and NLRP3(P<0.01).Additionally,the IL-1β and IL-18 were significantly reduced(P<0.01).CONCLUSION:Jiedu Shengji ointment alleviates excessive ERS and mitigates chronic inflammato-ry responses,thereby promoting the healing of diabetic wounds.These effects may be attributed to the inhibition of exces-sive activation of the PERK/IRE1/NLRP3 pathway.

Objective:To explore the survival status and economic burden of disease for patients with Cryopyrin Associated Periodic Syndrome(CAPS)in China.Methods:From August 2023 to February 2024,a questionnaire survey was conducted on patients who volunteered to participate.The survey included patients'sociodemographic characteristics,current medical treatment status,disease economic burden and life quality.Results:A total of 35 valid questionnaires were collected.The average age of onset for the patients was 5.67 years,and the average duration from onset to confirmed diagnosis was 7.63 years.The average total medical cost per person in the past 12 months was 82 532.79 yuan,which is significantly higher than the national per capita disposable income of China in 2023.Conclusion:CAPS has an early onset and a long duration until diagnosis,with treatment primarily symptomatic,resulting in a heavy disease burden for patients and their families.

Objective:to investigate the expression of integrin αvβ3 and osteopontin(OPN)in decidual tissues in missed abortion women with polycystic ovarian syndrome(PCOS).Methods:PCOS women with missed abor-tion(PCOS missed abortion group),non-PCOS with missed abortion(non-PCOS missed abortion group)and women with normal early pregnancy induced abortion(normal control group)who were admitted to the First Affili-ated Hospital of Xi'an Jiaotong University from February 2018 to December 2022 were selected as participants,and 20 subjects in each group.The expressions of integrin αvβ3 and OPN in decidual tissues among the three groups were detected.Correlation analysis was conducted between the expression levels of integrin αvβ3 and OPN in PCOS patients with missed abortion.Results:Integrin αvβ3 and OPN were mainly expressed in the epi-thelial cells of the uterus,as well as in decidual cells.There were significant differences in the positive rates and IHC scores of integrin αvβ3 and OPN in decidual tissues among the three groups(P<0.05).The positive rates and IHC scores in PCOS missed abortion group were significantly lower compared with non-PCOS missed abor-tion group and normal control group,and the difference was statistically significant(P<0.05),but there was no significant difference between non-PCOS missed abortion group and normal control group(P>0.05).The integrin αvβ3 and OPN in decidual tissues were mainly co-located in uterine epithelial cells.There were significant differ-ences in immunofluorescence intensity of integrin αvβ3 and OPN among the three groups(P<0.05).The missed abortion group of PCOS was significantly lower than that of non-PCOS missed abortion group and normal control group,and the difference was statistically significant(P<0.01).No significant difference was found between non-PCOS missed abortion group and normal control group(P>0.05).There were significant differences in the protein expression levels and mRNA expression levels of integrin αvβ3 and OPN in decidual tissue among the three groups(P<0.05).PCOS missed abortion group was significantly lower than non-PCOS missed abortion group and normal control group,and the difference was statistically significant(P<0.01).There was no significant difference between non-PCOS missed abortion group and normal control group(P>0.05).The results of Pearson correlation analysis showed that the protein and mRNA expression levels of integrin αvβ3 and OPN in decidual tis-sue of PCOS patients with missed abortion were significantly positively correlated(r>0,P<0.01).Conclusions:The integrin αvβ3 and OPN were expressed in both epithelial cells of the uterus and decidual cells in early preg-nancy.The expressions of them were significantly decreased in decidual tissues of PCOS patients with missed a-bortion,which might be related to reduced endometrial receptivity.The role of integrin αvβ3 and OPN in the occur-rence of missed abortion needs further study.

The clinical data of an infant with chondrodysplasia accompanied by early-onset epilepsy and medial temporal lobe dysgenesis due to the FGFR3 gene mutation, who was treated in the Affiliated Hospital of Jining Medical University in March 2024 were retrospectively analyzed.The 9-day-old male infant presented with frequent apnea at 5 hours after birth and experienced first seizure at 24 hours after birth.Physical examination revealed short limbs.Magnetic resonance imaging (MRI) showed abnormal changes in bilateral temporal lobes, hippocampal structure and bilateral lateral ventricular temporal angles, so cerebral developmental abnormalities were considered in this child.Whole exome sequencing confirmed a heterozygous variation in the FGFR3 gene [c.1620C>A(p.Asn540Lys)].After receiving Phenobarbital monotherapy, the child still had frequent seizures, but the seizure was completely controlled after the additional use of Lvetiracetam.To August 2024, a total of 14 patients with achondroplasia, epilepsy, and medial temporal lobe dysplasia caused by FGFR3 gene mutations were identified.These patients typically experienced frequent seizures in early infancy, which could be accompanied by apnea and psychomotor retardation.MRI consistently showed abnormal development of bilateral temporal lobes and hippocampus.Seizures were hardly controlled by anti-seizure medications, and Phenobarbital was effective in some cases.Whole exome sequencing revealed gene variations of c.1620C>A or c. 1620C>G (p.Asn540Lys).Patients with achondroplasia caused by FGFR3 gene mutations may present with early-onset epilepsy and medial temporal lobe dysplasia.Early seizures are frequent and difficult to control, and Phenobarbital is effective in some cases.

AIM:This study aims to investigate the effects of Jiedu-Shengji ointment(JDSJG)on wound healing in diabetic rats by modulating the protein kinase R-like endoplasmic reticulum kinase(PERK)/inositol-requiring enzyme 1(IRE1)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway in the context of endoplasmic reticulum stress(ERS).METHODS:Male Sprague-Dawley rats were randomly assigned to four groups:control group,model group,detoxification muscle ointment group,and sulfadiazine silver cream group.All groups,except the control,were administered an intraperitoneal injection of 45 mg/kg streptozotocin to induce diabetes.The control and model groups received daily applications of normal saline,while the detoxification myogen ointment and sulfadiazine silver cream groups received their respective treatments daily.After dressing changes,wounds were bandaged with sterile gauze.Following 14 d of continuous treatment,wound healing was assessed and healing rates calculated.Histopathologi-cal changes in wound tissues were analyzed using HE staining.Transmission electron microscopy was utilized to observe the number,morphology,and swelling of endoplasmic reticulum in the wound tissues.The expression and distribution of PERK,IRE1 and thioredoxin interacting protein(TXNIP)was assessed by immunohistochemistry,while Western blot was used to measure the levels of apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),TXNIP and NLRP3.ELISA was conducted to quantify the inflammatory cytokines interleukin-18(IL-18)and IL-1β.RE-SULTS:After 14 d of intervention,significant differences were observed in wound tissue parameters across the groups.The model group exhibited a significantly lower wound healing rate compared to the control group(P<0.01),with in-creased wound exudation,poor granulation tissue growth,and elevated the protein levels of PERK,IRE1,TXNIP,CHOP,NLRP3 and ASC(P<0.01),as well as significantly higher levels of IL-1β and IL-18(P<0.01).In contrast,the detoxification muscle ointment group showed a marked improvement in wound healing rate(P<0.01),reduced inflamma-tory exudation,improved granulation tissue growth,and significant decreases in TXNIP expression(P<0.01),along with lower levels of PERK,IRE1,CHOP,ASC and NLRP3(P<0.01).Additionally,the IL-1β and IL-18 were significantly reduced(P<0.01).CONCLUSION:Jiedu Shengji ointment alleviates excessive ERS and mitigates chronic inflammato-ry responses,thereby promoting the healing of diabetic wounds.These effects may be attributed to the inhibition of exces-sive activation of the PERK/IRE1/NLRP3 pathway.

Objective:To explore the survival status and economic burden of disease for patients with Cryopyrin Associated Periodic Syndrome(CAPS)in China.Methods:From August 2023 to February 2024,a questionnaire survey was conducted on patients who volunteered to participate.The survey included patients'sociodemographic characteristics,current medical treatment status,disease economic burden and life quality.Results:A total of 35 valid questionnaires were collected.The average age of onset for the patients was 5.67 years,and the average duration from onset to confirmed diagnosis was 7.63 years.The average total medical cost per person in the past 12 months was 82 532.79 yuan,which is significantly higher than the national per capita disposable income of China in 2023.Conclusion:CAPS has an early onset and a long duration until diagnosis,with treatment primarily symptomatic,resulting in a heavy disease burden for patients and their families.