Objective:To investigate the distribution of pathogens and changes in serum levels of pyruvate kinase isozyme type M2 (PKM2) and Galectin-3 in patients with severe trauma complicated by ventilator-associated pneumonia (VAP).Methods:A total of 139 patients with severe trauma and underwent mechanical ventilation in Zhangjiakou First Hospital from February 2022 to February 2024 were selected as the study subjects. They were divided into the VAP group (57 cases) and non- VAP group (82 cases) based on whether they developed VAP. The distribution of pathogenic bacteria in the VAP group was analyzed. Enzyme-linked immunosorbent assay (ELISA) method was applied to determine the expression levels of serum PKM2 and Galectin-3. Multivariate Logistic regression was applied to analyze the influencing factors of VAP in patients with severe trauma. Receiver operator characteristic (ROC) curve was applied to analyze the diagnostic value of serum PKM2 and Galectin-3 levels for severe trauma complicated by VAP.Results:Seventy-one strains of pathogenic bacteria were isolated from 57 patients in the VAP group, mainly including Gram positive bacteria (36.62%), Gram negative bacteria (59.15%), and fungi (4.23%). Among them, Gram positive bacteria were mainly Staphylococcus epidermidis and Staphylococcus aureus, Gram negative bacteria were mainly Acinetobacter baumannii and Klebsiella pneumoniae, and fungi were mainly tropical Candida and Candida albicans. The proportion of history of diabetes, the proportion of eating through nasogastric tube, the proportion of trauma severity score ≥ 16 and the levels of serum PKM2 and Galectin-3 in the VAP group were higher than those in the non- VAP group: 54.39%(31/57) vs. 32.93%(27/82), 82.46%(47/57) vs. 52.44%(43/82), 66.67%(38/57) vs. 24.39%(20/82), (32.46 ± 7.28) μg/L vs. (24.25 ± 6.17) μg/L, (3.26 ± 0.75) ng/L vs. (2.39 ± 0.61) ng/L, there were statistical differences ( P<0.05). Serum PKM2, Galectin-3, history of diabetes, nasal feeding mode and trauma severity score were the influencing factors of severe trauma patients complicated by VAP ( P<0.05). The area under the curve (AUC) of serum PKM2, Galectin-3, and their combination in predicting severe trauma complicated by VAP was 0.90, and the combination of the two was superior to their respective individual diagnoses ( Zcombination - PKM2 = 2.00, Zcombination - Galectin-3 = 1.99, P = 0.046, 0.047), its sensitivity and specificity were 92.98% and 84.15%, respectively. Conclusions:The distribution of urinary tract pathogens in patients with severe trauma complicated by VAP is mainly Gram negative bacteria, and serum PKM2 and Galectin-3 levels are obviously increased in patients with severe trauma complicated by VAP . The combination of the two has higher diagnostic value for severe trauma complicated by VAP and certain clinical application value.

Aim To explore the clinical efficacy of sequential balloon pulmonary angioplasty(BPA)in the treat-ment of patients with chronic thromboembolic pulmonary hypertension(CTEPH),and analyze the safety during the periop-erative period.Methods 30 patients with CTEPH who underwent BPA treatment at Luoyang Central Hospital affiliated to Zhengzhou University from August 2018 to February 2024 were selected,30 patients with CTEPH who chose drug treatment were set as controls,the patients'gender,age,body mass index,comorbidities,plasma N-terminal pro-brain natriuretic peptide(NT-proBNP)levels,application of pulmonary hypertension targeted drugs,6-minute walking dis-tance(6-MWD),WHO cardiac function classification and cardiac ultrasound pulmonary arterial pressure related data were collected.Right heart catheterization was performed to obtain pulmonary hemodynamic parameters in the BPA group.Changes in WHO cardiac function classification,6-MWD,NT-proBNP,pulmonary vascular hemodynamic parameters and cardiac ultrasound pulmonary artery pressure data before BPA,after the final BPA and at 6-month follow-up were com-pared,as well as differences between the two groups.The occurrence and management results of surgical complications such as pulmonary artery injury,contrast nephropathy and reperfusion pulmonary edema were recorded.Results Compared with before BPA,after the last BPA,cardiac output(CO),cardiac index(CI),and mixed venous oxygen satu-ration(SvO2)increased,mean pulmonary artery pressure(mPAP)and pulmonary vascular resistance(PVR)decreased(all P＜0.05),and 6-MWD,NT-proBNP,right ventricular diameter,right atrial up-down diameter,right atrial left-right diameter,left ventricular diastolic end diameter,and tricuspid regurgitation velocity all improved(all P＜0.05).Com-pared with the control group,the surgical group showed an increase in 6-MWD,a decrease in NT-proBNP levels,a de-crease in right ventricular diameter,right atrial up-down diameter and right atrial left-right diameter,an increase in left ventricular end diastolic diameter,a decrease in tricuspid regurgitation velocity and a significant improvement in WHO car-diac function classification(all P＜0.05).Among 30 BPA patients,2 patients experienced hemoptysis during surgery,1 patient developed reperfusion pulmonary edema after surgery,and 1 patient developed contrast nephropathy.After treat-ment,all patients improved and were discharged.Conclusion Sequential BPA has good clinical efficacy and safety in the treatment of CTEPH patients,and is an effective technique for treating CTEPH,which is worth promoting in clinical practice.

This study systematically collated and textual researched realgar from aspects such as name,origin,and quality by consulting ancient herbal texts,classic medical books,and modern literature.The textual research shows that current herbal works all take"realgar"as the official name,with aliases including"Huangshi shi","Shihuang","Tianyang shi","Jiguan shi","Xunhuang","Chouhuang",and"Mingxiong",etc.Ancient herbal records indicate that Xunhuang,Chouhuang,and Shuiku Realgar are all Realgar,while Orpiment is its associated mineral.In ancient times,the main production areas of Realgar were in Gansu,with outputs also seen in Shandong and Hunan.Nowadays,it is mainly produced in Hunan,Guizhou,Hubei,Gansu,Yunnan,Sichuan and other regions.Ancient herbal works mentioned characteristics like"cockscomb color","non-stinky","solid","red and bright"in their quality evaluation,while modern herbal works mostly evaluate its quality by color and texture,such as"red color","large blocks","brittle texture","glossy".The traditional efficacy of Realgar is to dry dampness,kill insects,detoxify various poisons,treat sores and activate blood.Modern studies have shown it also has anti-tumor,antibacterial and antiviral effects.Processing methods in past dynasties included water grinding,vinegar processing,refining,etc.,and currently,water grinding and acid water grinding are commonly used.This paper observed the properties of Realgar,detected the content of As?S?,and analyzed the microscopic characteristics and far-infrared spectral characteristics of qualified batches of Realgar.It was finally found that the As?S? content of qualified batches of Realgar was all more than 90%;under the scanning electron microscope,it showed massive shape,uniform distribution,obvious particles,and no agglomeration;a small amount of associated mineral Orpiment crystals were observed under the polarizing microscope;the characteristic peaks of Realgar(343-344 cm?1,224-225 cm?1,372-374 cm?1,367-369 cm?1,359 cm?1,207-208 cm?1,193-194 cm?1,168-170 cm?1)and Orpiment(390 cm?1,380 cm?1,347 cm?1,311 cm?1,300 cm?1,201 cm?1,182 cm?1,158 cm?1 and 139 cm?1)were determined."Red color and glossy"can be used as property references,"Realgar is a sulfide mineral of the Realgar family,with the main chemical component As?S?,associated with Orpiment"can be used as origin references,and"Shimen in Hunan,Wanshan in Guizhou,Yunnan,Gansu,Sichuan"can be used as production area references,which are consistent with the results of herbal textual research.This study provides a basis for the identification and analysis of Realgar,with a view to better guiding clinical medication and resource utilization.

Objective:To investigate the role of WW domain containing E3 ubiquitin protein ligase 1 (WWP1) in enamel development of mice.Methods:Single-cell RNA sequencing data of incisor tissues of postnatal day 7 (P7) mice and mandibular first molar tooth germs of P3.5 mice were used to analyze the expression of Wwp1 in dental epithelial cells. Immunohistochemistry was performed to observe the distribution and expression levels of WWP1 in the epithelium of mouse incisors and mandibular first molar tooth germs. Wwp1 knockout (Wwp1 KO) mice were generated and collected with their control littermates at P1, P7, three mice per group, as well as at P14, P28, 2 months (2M), and 3M, six mice per group. The enamel volumes of molars and incisors were analyzed using micro-CT. Scanning electron microscopy was employed to examine the enamel cross-sections of Wwp1 KO and control mice. Energy dispersive spectroscopy (EDS) was used to analyze the calcium and phosphorus content of the enamel rod of incisors. Immunofluorescence was performed to detect the expression of amelogenin (AMELX) in the ameloblasts of Wwp1 KO and control mice. Additionally, LS-8 ameloblast-like epithelial cells were cultured, and Wwp1 siRNA or overexpression plasmids were transfected to knock down or overexpress WWP1. The protein levels of AMELX were then assessed by Western blotting.Results:Single-cell sequencing result showed a high Wwp1 mRNA expression level in the epithelial cells of mouse incisors and mandibular molar tooth germs. Immunohistochemistry revealed the expression of WWP1 in presecretory, secretory, transitional, and mature ameloblasts. Wwp1 KO mice exhibited enamel developmental defects. The enamel volumes of molars and incisors in Wwp1 KO mice [(0.155±0.016), (0.300±0.017) μm 3] were reduced by 23.95% ( P<0.001) and 28.31% ( P<0.001) compared with the control group [(0.203±0.062), (0.418±0.023) μm 3] respectively. Scanning electron microscopy showed disorganized enamel structures in Wwp1 KO incisors and molars. EDS results showed the weight percent of calcium in the enamel rod of incisors decreased in Wwp1 KO mice [(20.74±0.91)%] compared with the control group [(30.30±3.83)%] ( P<0.001), and the calcium-to-phosphorus ratio decreased in Wwp1 KO mice (1.93±0.01) compared with the control group (2.02±0.01) ( P<0.001). Immunofluorescence showed weaker AMELX expression in ameloblasts of mandibular first molar tooth germs from P1 and P7 Wwp1 KO mice compared with the control group ( P<0.001, P<0.001). In LS-8 cells, Wwp1 knocked-down led to a decrease of AMELX protein expression, while WWP1 overexpression resulted in an increased AMELX protein level. Conclusions:WWP1 promotes ameloblast differentiation and enamel matrix mineralization, playing a critical role in enamel formation.

Objective:To investigate the reference intervals of serum uric acid levels in normal-weight children and analyze the factors influencing these levels.Methods:In this cross-sectional study, clinical data were collected from 7 910 normal-weight children, aged 1 month to 15 years, who underwent health check-ups at the Children′s Hospital of Zhejiang University School of Medicine between August 2013 and August 2023. Data included sex, age, pubertal signs, blood pressure, and serum uric acid levels. The participants were categorized into 4 age groups: 1-<12 months, 1-<6 years, 6-<11 years, and 11-<16 years, and were further analyzed by sex. The P5 and P95 percentiles of uric acid values were defined as the lower and upper limits of the reference interval, respectively. Correlation analysis and partial correlation analysis were used to assess the relationship between uric acid and other variables such as age, body mass index Z value, and Tanner stage. Multivariate linear regression was used to compare uric acid levels across gender and age groups, respectively. Results:Among the 7 910 children, the distribution across age groups was as follows: 562 (317 boys) in 1-<12 months, 4 120 (2 366 boys) in 1-<6 years, 2 357 (1 432 boys) in 6-<11 years, and 871 (536 boys) in 11-<16 years, the uric acid levels in boys were significantly higher than those in girls ( P<0.05). Uric acid levels exhibited a positive correlation with age ( r=0.47 , 0.20, both P<0.001), and a weak positive correlation with BMI Z-scores(both r=0.11, P<0.001). Among participants aged 6-<11 years and 11-<16 years, uric acid levels in boys were positively correlated with Tanner stage ( r=0.10, 0.27, both P<0.05), but no significant correlation was observed in girls (all P>0.05). The uric acid levels were significantly higher in boys than in girls in the 1-<12 months, 1-<6 years and 11-<16 years age groups (all P<0.05), but no significant gender difference was found in the 6-<11 years groups ( P>0.05). Uric acid levels exhibited statistically significant variations among age groups ( P<0.001). The reference intervals of uric acid values were as follows in 1-<12 months age group, 157-335 μmol/L for boys and 160-315 μmol/L for girls; in 1-<6 years age group, 180-359 μmol/L for boys and 180-355 μmol/L for girls; in 6-<11 years group, 190-375 μmol/L; in 11-<16 years age group, 237-480 μmol/L for boys and 218-410 μmol/L for girls. Conclusions:Reference intervals for uric acid varying significantly across different pediatric age groups. Sex, and pubertal development status are closely related to uric acid levels.

Urolithiasis represents a prevalent clinical challenge marked by high recurrence rates and morbidity，with existing preventive strategies struggling to effectively curb its epidemic trajectory，thereby posing a significant threat to public health. The etiology of this condition is intricate，involving a complex network of interactions spanning classical supersaturation-crystallization theory，Randall’s plaque theory，and multifactorial elements such as cellular injury，inflammatory responses，metabolic derangements，the gut-kidney axis，immune dysregulation，and genetic predisposition. However，the critical mechanisms initiating stone formation and the early pathophysiological processes remain incompletely elucidated，constituting the core impasse in current preventive strategies. This review systematically synthesizes classical theories and cutting-edge advancements in urolithiasis etiology research，emphasizing the urgent need to integrate emerging technologies，including high-dimensional omics，advanced imaging modalities，and artificial intelligence，to dissect pivotal pathological nodes in early stone formation. Such interdisciplinary efforts are essential to overcome cognitive bottlenecks and ultimately achieve personalized，precision-based prevention strategies.

Aim To explore the clinical efficacy of sequential balloon pulmonary angioplasty(BPA)in the treat-ment of patients with chronic thromboembolic pulmonary hypertension(CTEPH),and analyze the safety during the periop-erative period.Methods 30 patients with CTEPH who underwent BPA treatment at Luoyang Central Hospital affiliated to Zhengzhou University from August 2018 to February 2024 were selected,30 patients with CTEPH who chose drug treatment were set as controls,the patients'gender,age,body mass index,comorbidities,plasma N-terminal pro-brain natriuretic peptide(NT-proBNP)levels,application of pulmonary hypertension targeted drugs,6-minute walking dis-tance(6-MWD),WHO cardiac function classification and cardiac ultrasound pulmonary arterial pressure related data were collected.Right heart catheterization was performed to obtain pulmonary hemodynamic parameters in the BPA group.Changes in WHO cardiac function classification,6-MWD,NT-proBNP,pulmonary vascular hemodynamic parameters and cardiac ultrasound pulmonary artery pressure data before BPA,after the final BPA and at 6-month follow-up were com-pared,as well as differences between the two groups.The occurrence and management results of surgical complications such as pulmonary artery injury,contrast nephropathy and reperfusion pulmonary edema were recorded.Results Compared with before BPA,after the last BPA,cardiac output(CO),cardiac index(CI),and mixed venous oxygen satu-ration(SvO2)increased,mean pulmonary artery pressure(mPAP)and pulmonary vascular resistance(PVR)decreased(all P＜0.05),and 6-MWD,NT-proBNP,right ventricular diameter,right atrial up-down diameter,right atrial left-right diameter,left ventricular diastolic end diameter,and tricuspid regurgitation velocity all improved(all P＜0.05).Com-pared with the control group,the surgical group showed an increase in 6-MWD,a decrease in NT-proBNP levels,a de-crease in right ventricular diameter,right atrial up-down diameter and right atrial left-right diameter,an increase in left ventricular end diastolic diameter,a decrease in tricuspid regurgitation velocity and a significant improvement in WHO car-diac function classification(all P＜0.05).Among 30 BPA patients,2 patients experienced hemoptysis during surgery,1 patient developed reperfusion pulmonary edema after surgery,and 1 patient developed contrast nephropathy.After treat-ment,all patients improved and were discharged.Conclusion Sequential BPA has good clinical efficacy and safety in the treatment of CTEPH patients,and is an effective technique for treating CTEPH,which is worth promoting in clinical practice.

This study systematically collated and textual researched realgar from aspects such as name,origin,and quality by consulting ancient herbal texts,classic medical books,and modern literature.The textual research shows that current herbal works all take"realgar"as the official name,with aliases including"Huangshi shi","Shihuang","Tianyang shi","Jiguan shi","Xunhuang","Chouhuang",and"Mingxiong",etc.Ancient herbal records indicate that Xunhuang,Chouhuang,and Shuiku Realgar are all Realgar,while Orpiment is its associated mineral.In ancient times,the main production areas of Realgar were in Gansu,with outputs also seen in Shandong and Hunan.Nowadays,it is mainly produced in Hunan,Guizhou,Hubei,Gansu,Yunnan,Sichuan and other regions.Ancient herbal works mentioned characteristics like"cockscomb color","non-stinky","solid","red and bright"in their quality evaluation,while modern herbal works mostly evaluate its quality by color and texture,such as"red color","large blocks","brittle texture","glossy".The traditional efficacy of Realgar is to dry dampness,kill insects,detoxify various poisons,treat sores and activate blood.Modern studies have shown it also has anti-tumor,antibacterial and antiviral effects.Processing methods in past dynasties included water grinding,vinegar processing,refining,etc.,and currently,water grinding and acid water grinding are commonly used.This paper observed the properties of Realgar,detected the content of As?S?,and analyzed the microscopic characteristics and far-infrared spectral characteristics of qualified batches of Realgar.It was finally found that the As?S? content of qualified batches of Realgar was all more than 90%;under the scanning electron microscope,it showed massive shape,uniform distribution,obvious particles,and no agglomeration;a small amount of associated mineral Orpiment crystals were observed under the polarizing microscope;the characteristic peaks of Realgar(343-344 cm?1,224-225 cm?1,372-374 cm?1,367-369 cm?1,359 cm?1,207-208 cm?1,193-194 cm?1,168-170 cm?1)and Orpiment(390 cm?1,380 cm?1,347 cm?1,311 cm?1,300 cm?1,201 cm?1,182 cm?1,158 cm?1 and 139 cm?1)were determined."Red color and glossy"can be used as property references,"Realgar is a sulfide mineral of the Realgar family,with the main chemical component As?S?,associated with Orpiment"can be used as origin references,and"Shimen in Hunan,Wanshan in Guizhou,Yunnan,Gansu,Sichuan"can be used as production area references,which are consistent with the results of herbal textual research.This study provides a basis for the identification and analysis of Realgar,with a view to better guiding clinical medication and resource utilization.

Objective:To investigate the role of WW domain containing E3 ubiquitin protein ligase 1 (WWP1) in enamel development of mice.Methods:Single-cell RNA sequencing data of incisor tissues of postnatal day 7 (P7) mice and mandibular first molar tooth germs of P3.5 mice were used to analyze the expression of Wwp1 in dental epithelial cells. Immunohistochemistry was performed to observe the distribution and expression levels of WWP1 in the epithelium of mouse incisors and mandibular first molar tooth germs. Wwp1 knockout (Wwp1 KO) mice were generated and collected with their control littermates at P1, P7, three mice per group, as well as at P14, P28, 2 months (2M), and 3M, six mice per group. The enamel volumes of molars and incisors were analyzed using micro-CT. Scanning electron microscopy was employed to examine the enamel cross-sections of Wwp1 KO and control mice. Energy dispersive spectroscopy (EDS) was used to analyze the calcium and phosphorus content of the enamel rod of incisors. Immunofluorescence was performed to detect the expression of amelogenin (AMELX) in the ameloblasts of Wwp1 KO and control mice. Additionally, LS-8 ameloblast-like epithelial cells were cultured, and Wwp1 siRNA or overexpression plasmids were transfected to knock down or overexpress WWP1. The protein levels of AMELX were then assessed by Western blotting.Results:Single-cell sequencing result showed a high Wwp1 mRNA expression level in the epithelial cells of mouse incisors and mandibular molar tooth germs. Immunohistochemistry revealed the expression of WWP1 in presecretory, secretory, transitional, and mature ameloblasts. Wwp1 KO mice exhibited enamel developmental defects. The enamel volumes of molars and incisors in Wwp1 KO mice [(0.155±0.016), (0.300±0.017) μm 3] were reduced by 23.95% ( P<0.001) and 28.31% ( P<0.001) compared with the control group [(0.203±0.062), (0.418±0.023) μm 3] respectively. Scanning electron microscopy showed disorganized enamel structures in Wwp1 KO incisors and molars. EDS results showed the weight percent of calcium in the enamel rod of incisors decreased in Wwp1 KO mice [(20.74±0.91)%] compared with the control group [(30.30±3.83)%] ( P<0.001), and the calcium-to-phosphorus ratio decreased in Wwp1 KO mice (1.93±0.01) compared with the control group (2.02±0.01) ( P<0.001). Immunofluorescence showed weaker AMELX expression in ameloblasts of mandibular first molar tooth germs from P1 and P7 Wwp1 KO mice compared with the control group ( P<0.001, P<0.001). In LS-8 cells, Wwp1 knocked-down led to a decrease of AMELX protein expression, while WWP1 overexpression resulted in an increased AMELX protein level. Conclusions:WWP1 promotes ameloblast differentiation and enamel matrix mineralization, playing a critical role in enamel formation.

Objective:To investigate the distribution of pathogens and changes in serum levels of pyruvate kinase isozyme type M2 (PKM2) and Galectin-3 in patients with severe trauma complicated by ventilator-associated pneumonia (VAP).Methods:A total of 139 patients with severe trauma and underwent mechanical ventilation in Zhangjiakou First Hospital from February 2022 to February 2024 were selected as the study subjects. They were divided into the VAP group (57 cases) and non- VAP group (82 cases) based on whether they developed VAP. The distribution of pathogenic bacteria in the VAP group was analyzed. Enzyme-linked immunosorbent assay (ELISA) method was applied to determine the expression levels of serum PKM2 and Galectin-3. Multivariate Logistic regression was applied to analyze the influencing factors of VAP in patients with severe trauma. Receiver operator characteristic (ROC) curve was applied to analyze the diagnostic value of serum PKM2 and Galectin-3 levels for severe trauma complicated by VAP.Results:Seventy-one strains of pathogenic bacteria were isolated from 57 patients in the VAP group, mainly including Gram positive bacteria (36.62%), Gram negative bacteria (59.15%), and fungi (4.23%). Among them, Gram positive bacteria were mainly Staphylococcus epidermidis and Staphylococcus aureus, Gram negative bacteria were mainly Acinetobacter baumannii and Klebsiella pneumoniae, and fungi were mainly tropical Candida and Candida albicans. The proportion of history of diabetes, the proportion of eating through nasogastric tube, the proportion of trauma severity score ≥ 16 and the levels of serum PKM2 and Galectin-3 in the VAP group were higher than those in the non- VAP group: 54.39%(31/57) vs. 32.93%(27/82), 82.46%(47/57) vs. 52.44%(43/82), 66.67%(38/57) vs. 24.39%(20/82), (32.46 ± 7.28) μg/L vs. (24.25 ± 6.17) μg/L, (3.26 ± 0.75) ng/L vs. (2.39 ± 0.61) ng/L, there were statistical differences ( P<0.05). Serum PKM2, Galectin-3, history of diabetes, nasal feeding mode and trauma severity score were the influencing factors of severe trauma patients complicated by VAP ( P<0.05). The area under the curve (AUC) of serum PKM2, Galectin-3, and their combination in predicting severe trauma complicated by VAP was 0.90, and the combination of the two was superior to their respective individual diagnoses ( Zcombination - PKM2 = 2.00, Zcombination - Galectin-3 = 1.99, P = 0.046, 0.047), its sensitivity and specificity were 92.98% and 84.15%, respectively. Conclusions:The distribution of urinary tract pathogens in patients with severe trauma complicated by VAP is mainly Gram negative bacteria, and serum PKM2 and Galectin-3 levels are obviously increased in patients with severe trauma complicated by VAP . The combination of the two has higher diagnostic value for severe trauma complicated by VAP and certain clinical application value.