Objective To investigate the expression and roles of serine/threonine and tyrosine kinases(TTK)and mouse dual microbody 2(MDM2)in cervical lesion tissue.Methods Patients(n=180)who underwent gynecological surgery at the First Affiliated Hospital of Henan University of Science and Technology from June 2022 to January 2024 were evaluated,including 50 patients in the cervical cancer group,50 patients in the high-grade lesion group,40 patients in the low-grade lesion group,and 40 patients in the non-cervical lesion(control)group.The mRNA expression and protein levels of TTK and MDM2 in each group were detected and compared by real-time quantitative PCR and immunohistochemistry,respectively.The diagnostic value of the mRNA expression levels of TTK and MDM2 in cer-vical cancer was analyzed using receiver operating characteristic curves.Results The mRNA levels of TTK and MDM2 significantly dif-fered among the four groups(P＜0.05);with increases in the lesion grade,the mRNA levels of TTK and MDM2 increased gradually and showed significant differences(P＜0.05).Immunohistochemical results showed that TTK was mainly located in the cytoplasm,whereas MDM2 was mainly located in the nucleus,with positive expression rates in cervical cancer tissues of 84.00％and 90.00％,respectively.These values were higher than those in other pathological tissues(P＜0.05).The mRNA levels of TTK and MDM2 were significantly cor-related with the degree of differentiation and lymph node metastasis(P＜0.05).The receiver operating characteristic curve showed that the areas under the curve of TTK and MDM2 mRNA for diagnosing cervical cancer were 0.803 and 0.798,respectively.Additionally,the area under the curve of the combined diagnosis was 0.912,which was higher than that observed for single detection(Z=2.230,2.553,P＜0.05).Conclusion The mRNA expression of TTK and MDM2 and their corresponding protein levels were increased in cervical lesions,demonstrating their potential as biological indicators for the clinical diagnosis of cervical cancer.

Mesenchymal stem cells(MSCs)are multipotent stromal cells that possess the capacity for self-renewal and differentiation into multiple cell lineages.Due to the ease of procurement,robust expansion in vitro,the multipotency,they are recognized as a vital source of stem cells in the field of regenerative medicine.MSCs can be isolated from various tissues,including bone marrow,adipose tissue,and umbilical cord.Research indicates that Human umbilical cord mesenchymal stem cells(hUCMSCs)play an effective role in wound healing and tissue regeneration,and can be utilized for the repair of skin wounds.They are also considered to be the most promising seed cells for skin tissue engineering.This review aims to provide an overview of the biological characteristics of hUCMSCs,the mechanisms in promoting skin wound healing,and their clinical applications.

Mesenchymal stem cells(MSCs)are multipotent stromal cells that possess the capacity for self-renewal and differentiation into multiple cell lineages.Due to the ease of procurement,robust expansion in vitro,the multipotency,they are recognized as a vital source of stem cells in the field of regenerative medicine.MSCs can be isolated from various tissues,including bone marrow,adipose tissue,and umbilical cord.Research indicates that Human umbilical cord mesenchymal stem cells(hUCMSCs)play an effective role in wound healing and tissue regeneration,and can be utilized for the repair of skin wounds.They are also considered to be the most promising seed cells for skin tissue engineering.This review aims to provide an overview of the biological characteristics of hUCMSCs,the mechanisms in promoting skin wound healing,and their clinical applications.

Objective:To evaluate the efficacy of preoperative prediction of regional lymph node (RLN) metastasis in renal cell carcinoma (RCC) using a machine learning model based on habitat imaging radiomics from renal MRI.Methods:This cross-sectional study retrospectively analyzed 220 patients with RCC who underwent nephrectomy and RLN dissection at four medical centers of Chinese PLA General Hospital from January 2010 to August 2023. The cohort included 65 patients with RLN metastasis and 155 without. A stratified random sampling method was used to divide 175 patients from the first medical center into a training set ( n=140) and an internal test set ( n=35) in an 8∶2 ratio, while 45 patients from the third, fourth, and fifth medical centers constituted the external test set. The primary RCC lesions were categorized into 15 habitat subregions based on corticomedullary-phase enhancement and T 2WI signal intensity on MRI, and the volume fractions of different subregions were analyzed. In the training cohort, radiomics features derived from the habitat subregions were used to construct a radiomics model employing various machine learning algorithms, including extremely random trees (ET), gradient boosting decision trees (GBDT), random forest (RF), and support vector machine (SVM). The optimal model was selected and combined with RLN short-axis diameter to develop a combined model. The efficacy of each model in predicting RLN metastasis was evaluated using the receiver operating characteristic (ROC) curve. Results:The volume fraction of hyper-enhanced hyper-intense regions in the non-metastatic group was significantly higher than that in the metastatic group (0.05±0.09 vs. 0.02±0.03; t=3.00, P=0.003). Among the machine learning models constructed using 15 optimal habitat radiomics features, the SVM model demonstrated the best performance, with area under the ROC curve (AUC) values of 0.85 (95% CI 0.72-0.98) in the internal test set and 0.82 (95% CI 0.67-0.98) in the external test set, surpassing those of the ET, GBDT, and RF models. The combined model, integrating the SVM model with RLN short-axis diameter, achieved AUC values of 0.94 (95% CI 0.85-1.00) in the internal test set and 0.89 (95% CI 0.78-1.00) in the external test set, with RLN short-axis diameter contributing AUC values of 0.81 (95% CI 0.66-0.96) and 0.81 (95% CI 0.68-0.94), respectively. The diagnostic sensitivity of the combined model was 91.7% in the internal test set and 85.7% in the external test set, with specificities of 78.3% and 67.7%, respectively. Conclusion:The combined model based on MRI habitat imaging radiomics and RLN short-axis diameter demonstrates excellent preoperative assessment capability for RLN metastasis in RCC.

Objective To investigate the expression and roles of serine/threonine and tyrosine kinases(TTK)and mouse dual microbody 2(MDM2)in cervical lesion tissue.Methods Patients(n=180)who underwent gynecological surgery at the First Affiliated Hospital of Henan University of Science and Technology from June 2022 to January 2024 were evaluated,including 50 patients in the cervical cancer group,50 patients in the high-grade lesion group,40 patients in the low-grade lesion group,and 40 patients in the non-cervical lesion(control)group.The mRNA expression and protein levels of TTK and MDM2 in each group were detected and compared by real-time quantitative PCR and immunohistochemistry,respectively.The diagnostic value of the mRNA expression levels of TTK and MDM2 in cer-vical cancer was analyzed using receiver operating characteristic curves.Results The mRNA levels of TTK and MDM2 significantly dif-fered among the four groups(P＜0.05);with increases in the lesion grade,the mRNA levels of TTK and MDM2 increased gradually and showed significant differences(P＜0.05).Immunohistochemical results showed that TTK was mainly located in the cytoplasm,whereas MDM2 was mainly located in the nucleus,with positive expression rates in cervical cancer tissues of 84.00％and 90.00％,respectively.These values were higher than those in other pathological tissues(P＜0.05).The mRNA levels of TTK and MDM2 were significantly cor-related with the degree of differentiation and lymph node metastasis(P＜0.05).The receiver operating characteristic curve showed that the areas under the curve of TTK and MDM2 mRNA for diagnosing cervical cancer were 0.803 and 0.798,respectively.Additionally,the area under the curve of the combined diagnosis was 0.912,which was higher than that observed for single detection(Z=2.230,2.553,P＜0.05).Conclusion The mRNA expression of TTK and MDM2 and their corresponding protein levels were increased in cervical lesions,demonstrating their potential as biological indicators for the clinical diagnosis of cervical cancer.

Objective:To evaluate the efficacy of preoperative prediction of regional lymph node (RLN) metastasis in renal cell carcinoma (RCC) using a machine learning model based on habitat imaging radiomics from renal MRI.Methods:This cross-sectional study retrospectively analyzed 220 patients with RCC who underwent nephrectomy and RLN dissection at four medical centers of Chinese PLA General Hospital from January 2010 to August 2023. The cohort included 65 patients with RLN metastasis and 155 without. A stratified random sampling method was used to divide 175 patients from the first medical center into a training set ( n=140) and an internal test set ( n=35) in an 8∶2 ratio, while 45 patients from the third, fourth, and fifth medical centers constituted the external test set. The primary RCC lesions were categorized into 15 habitat subregions based on corticomedullary-phase enhancement and T 2WI signal intensity on MRI, and the volume fractions of different subregions were analyzed. In the training cohort, radiomics features derived from the habitat subregions were used to construct a radiomics model employing various machine learning algorithms, including extremely random trees (ET), gradient boosting decision trees (GBDT), random forest (RF), and support vector machine (SVM). The optimal model was selected and combined with RLN short-axis diameter to develop a combined model. The efficacy of each model in predicting RLN metastasis was evaluated using the receiver operating characteristic (ROC) curve. Results:The volume fraction of hyper-enhanced hyper-intense regions in the non-metastatic group was significantly higher than that in the metastatic group (0.05±0.09 vs. 0.02±0.03; t=3.00, P=0.003). Among the machine learning models constructed using 15 optimal habitat radiomics features, the SVM model demonstrated the best performance, with area under the ROC curve (AUC) values of 0.85 (95% CI 0.72-0.98) in the internal test set and 0.82 (95% CI 0.67-0.98) in the external test set, surpassing those of the ET, GBDT, and RF models. The combined model, integrating the SVM model with RLN short-axis diameter, achieved AUC values of 0.94 (95% CI 0.85-1.00) in the internal test set and 0.89 (95% CI 0.78-1.00) in the external test set, with RLN short-axis diameter contributing AUC values of 0.81 (95% CI 0.66-0.96) and 0.81 (95% CI 0.68-0.94), respectively. The diagnostic sensitivity of the combined model was 91.7% in the internal test set and 85.7% in the external test set, with specificities of 78.3% and 67.7%, respectively. Conclusion:The combined model based on MRI habitat imaging radiomics and RLN short-axis diameter demonstrates excellent preoperative assessment capability for RLN metastasis in RCC.

Objective To study the effect and mechanism of high glucose on mesothelial-mesenchymal transition(MMT)of peritoneal mesothelial cells(HMrSV5),and the protective effect of pharmacological blocking of signal transducer and activator of transcription 3(STAT3)on rat peritoneal fibrosis(PF)model.Methods The animals were divided into three groups:the sham group,the model group,and the STAT3 inhibitor group.A miniature per-itoneal dialysis catheter was implanted under the dorsal skin of rat and the rat peritoneal fibrosis model was induced by daily injection of high glucose dialysate.After 10 weeks,HE staining was used to evaluate the histology of the peritoneum,and the level of transforming growth factor-β1(TGF-β1)in the peritoneum was measured by immuno-histochemistry.HMrSV5 was cultured in high glucose and the optimal stimulation concentration of high glucose was determined by Western blot.High glucose was used to stimulate HMrSV5 after successful transfection with si-STAT3 and Western blot was used to measure the protein level of STAT3,p-STAT3,and the key enzymes of glycol-ysis 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)and lactate dehydrogenase A(LDHA).Results HE staining showed that administration of STAT3 inhibitor(BP-1-102)could inhibit the thickening of subperitoneal tissue and the proliferation of vessels in HG dialysis rats.The expression of TGF-β1 in the rats perito-neum of the model group was significantly higher than that in the sham group,and the level of TGF-β1 was marked-ly lower in the STAT3 inhibitor group compared to the model group(P<0.05).Compared to the control group,high glucose induced the up-regulation of α-smooth muscle actin(α-SMA),the down-regulation of E-cadherin and STAT3 activation in HMrSV5(P<0.05).Mesothelial cells treated with high glucose also exhibited high expres-sion of the key enzymes of glycolysis(PFKFB3,LDHA)(P<0.05),and si-STAT3 can effectively inhibit the overexpression of PFKFB3 and LDHA induced by high glucose(P<0.05).Conclusion STAT3 is involved in high glucose-induced HMrSV5 hyperglycolysis and MMT,and targeting STAT3 alleviates peritoneal fibrosis and an-giogenesis during peritoneal dialysis treatment in rats.

AIM:To investigate the role of proviral integration site for Moloney murine leukemia virus 1(PIM1)in the phenotypic switching of vascular smooth muscle cells(VSMCs)induced by oxidized low-density lipoprotein(oxLDL),and to explore the underlying mechanisms.METHODS:Eighteen male ApoE-/-mice(8 weeks old)were ran-domly divided into general diet group and high-fat diet group,with 9 mice per group.After 16 weeks,aortic samples were analyzed using HE staining to observe plaque formation.In vitro,VSMCs were exposed to oxLDL to induce phenotypic transformation.Western blot and immunofluorescence were used to measure the protein expression levels of PIM1 and phe-notypic markers including α-smooth muscle actin(α-SMA),smooth muscle protein 22α(SM22α),osteopontin(OPN),and CD68.Glycolysis levels were assessed by detecting the expression of glycolytic enzymes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase(PFKFB3)and hexokinase 2(HK2)by Western blot,and lactate secretion was measured using a lactate test kit.The effects of SMI-4a(a specific inhibitor of PIM1)and PIM1 small interfering RNA on oxLDL-in-duced phenotypic markers in VSMCs were evaluated.Moreover,the impact of 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one(3PO;a glycolysis inhibitor)on oxLDL-induced phenotypic switching and glycolysis in VSMCs was investigated.RESULTS:HE staining revealed atherosclerotic plaque formation in the aortas of ApoE-/-mice fed with high-fat diet.Im-munofluorescence showed high accumulation of PIM1 and OPN in the tunica intima of atherosclerotic plaques.Compared with control group,aortic plaques exhibited significantly elevated levels of PIM1,OPN and CD68 proteins(P<0.01),ac-companied by reduced expression of contractile phenotype markers α-SMA and SM22α(P<0.01).In vitro,oxLDL treat-ment led to gradual decrease in α-SMA and SM22α expression(P<0.05 or P<0.01),while OPN and CD68 expression in-creased(P<0.05 or P<0.01).Moreover,oxLDL significantly up-regulated the protein expression of PIM1,PFKFB3 and HK2,and increased lactate secretion in VSMCs(P<0.05 or P<0.01).Knockdown of PIM1 or treatment with SMI-4a markedly attenuated these oxLDL-induced effects on VSMCs(P<0.05 or P<0.01).Treatment with 3PO also abolished ox-LDL-induced phenotypic transformation and glycolysis in VSMCs(P<0.05 or P<0.01).CONCLUSION:PIM1 highly accumulates in the atherosclerotic plaques of ApoE-/-mice.The phenotypic transformation of VSMCs was correlated with the expression of PIM1.PIM1 can regulate the phenotypic transformation of oxLDL-treated VSMCs by inducing glycolysis.

Objective To investigate best timing of ultrasound-guided rectus sheath block in single-site laparoendoscopic surgery.Methods A total of 63 patients underwent elective single-site laparoendscopic surgery for benign gynecological tumors in Gynecology Ward of the Second Affiliated Hospital of Wenzhou Medical University from August 2021 to January 2022 were selected as study subjects.They were divided into Group E(32 cases)and Group O(31 cases)by using a random number table method.After excluding three cases,60 patients were finally admitted,with 30 cases in each group.Group E underwent preoperative ultrasound-guided rectus sheath block,and group O underwent postoperative ultrasound-guided rectus sheath block.Numerical rating scale(NRS)score of immediately after extubation(T1),12-hour after surgery(T2),and 24-hour after surgery(T3)in resting and active status were compared between two groups;mean arterial pressure and heart rate before and after incision were compared between two groups;intraoperative dose of remifentanil,postoperative oxycodone and rate of postoperative analgesic relief were compared between two groups;time of entry and operation were compared between two groups;and occurrence of nerve block complications in two groups was recorded.Results Overall analysis found that there were significant differences in comparison of time points and interaction of resting NRS scores in two groups(P<0.05),as well as there were significant differences in comparison of time points of active NRS scores in two groups(P<0.05).Further pairwise comparison,within-group comparison:NRS scores of rest status and active status at T2 and T3 in group O were significantly lower than those at T1(P<0.05);NRS scores for rest status at T3 was significantly lower than that at T1 in group E,and NRS scores for active status at T2 and T3 were significantly lower than those at T1 in group E(P<0.05).Comparison between groups:NRS scores for rest and active status at T1 were significantly lower in group E than that in group O(P<0.05).After skin incision,mean arterial pressure in group O was significantly higher than before skin incision,and heart rate in group O was significantly faster than before skin incision(P<0.05).No abdominal puncture,puncture site infection,local anesthetic poisoning,or other complications occurred in either group.Conclusion In single-site laparoendoscopic gynecological surgery,ultrasound-guided preoperative rectus sheath block can provide better analgesic effect for patients in the early postoperative stage,and changes in heart rate and mean arterial pressure before and after incision are smaller,which is worthy of recommendation.

Objective:To explore the risk signals of brigatinib-related adverse events (AEs) and provide reference for the safe use in clinical practice.Methods:The US FDA Adverse Event Reporting System database was searched and AE reports on brigatinib as the primary suspect drug from April 1, 2017 to March 31, 2022 were collected. AEs were standardized and classified according to the preferred terms (PT) and system organ class (SOC) of Medical Dictionary for Regulatory Activities 24.0. Reported odds ratio ( ROR) and proportional reporting odds ratio ( PRR) methods were used to mine the AE risk signals of brigatinib. An AE with reports ≥3, ROR≥2, 95% confidence interval ( CI) lower limit of ROR>1, or reports ≥3, PRR≥2, and χ2>4 was defined as a positive signal. Positive PT signals were analyzed using descriptive method. Results:A total of 1 564 AE reports were included in the analysis, involving 672 PTs. After analysis using ROR and PRR methods, 52 PTs with positive risk signals were obtained, involving 16 SOCs. The top 10 PTs in report amount were fatigue, diarrhea, nausea, cough, abnormal serum creatine phosphokinase, dyspnea, headache, rash, vomiting, and hypertension, all of which were common AEs in the instructions. The top 10 PTs in signal intensity were pituitary infarction, radiation necrosis, elevated amylase, esophageal varices, early saturation, elevated lipase, abnormal serum creatine phosphokinase, pulmonary toxicity, prolonged activated partial thromboplastin time, and photosensitivity. Among them, the PTs ranked 1st, 2nd, 4th, 5th, 8th, and 10th were not recorded in the label. Pneumonia and interstitial lung disease (ILD) were serious AEs, with 31 and 8 reports, respectively. In the 52 PTs, 28 were not included in the drug label, involving 12 SOCs. Conclusions:The main adverse reactions of brigatinib were diarrhea, nausea, cough, and abnormal serum creatine phosphokinase and serious adverse reactions such as pneumonia and ILD were both reported, which were consistent with the common AE recorded in the drug label. In addition, brigatinib might cause pituitary infarction, radiation necrosis, pulmonary toxicity, photosensitivity, etc., which should be vigilant in clinical practice.