Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Objective To investigate the imaging features of ultrasound,CT and air enema in children with intestinal duplications,and to improve the preoperative diagnosis rate.Methods The imaging data of 22 cases with intestinal duplications confirmed by operation and pathology were analyzed retrospectively.Results Fifteen cases underwent ultrasound,in which 12 cases showed cystic lesions,and the cyst wall showed typical"double ring sign"and"Y sign".12 cases underwent enhanced CT examination,in which 11 cases showed cystic lesions,and the enhancement pattern of the cyst wall was similar to that of intestinal wall.8 cases underwent CT plain scan examination,but only 3 cases showed cystic lesions and no characteristic signs were found.3 patients of secondary intussusceptions underwent air enema,in which 1 case of recurrent intussusceptions was unsuccessful,and 2 cases still showed masses in the ileocecal region after successful reduction.Conclusion CT plain scan has low diagnostic value for intestinal duplications in children,and the combination of ultrasound and CT enhanced examination can improve the preoperative diagnosis rate.For patients with recurrent intussusceptions and successful air enema reductions,if masses are still seen in the ileocecal region,the possibility of intestinal duplications should be considered.

Objective:To investigate the role of 20 MHz high-frequency ultrasound in evaluating scar thickness and morphology.Methods:The clinical data of patients with the initial stage of scar formation after burn trauma (<1 month), hypertrophic scar (1-6 months) and atrophic scar (>6 months) treated by the Department of Burn and Cutaneous Surgery, the First Affiliated Hospital of Air Force Medical University from April 2019 to December 2020, were retrospectively analyzed. All patients were evaluated by 20 MHz high-frequency ultrasound, histopathology and Vancouver scar scale (VSS). Three measurement points were randomly selected at the scar during ultrasonic examination, and the average value was recorded as the ultrasonic thickness measurement value. The scar tissue samples were collected from the site of ultrasonic examination, and HE staining and Masson staining were performed. At the same time, scar thickness was evaluated by two physicians using VSS. The difference of scar thickness assessment result among the 3 method in patients at the initial stage of scar formation, hypertrophic scar and atrophic scar was compared. Meanwhile, the relationship between the characteristics of 20 MHz high-frequency ultrasound and histopathology was compared. The measurement data of normal distribution were expressed as Mean±SD. One-way ANOVA was used for comparison among three groups, and SNK- q test was used for pairwise comparison between groups. Counting data were analyzed by Chi-square test. Results:A total of 224 patients were included, including 91 males and 133 females, aged from 1 to 34 years, with an average age of 25.7 years. There were 79 patients at the initial stage of scar formation, 102 at the hypertrophic stage, and 43 at the atrophic stage. (1) In the initial stage of scar formation, the thickness measured by 20 MHz ultrasound was about (2.01±0.68) mm, the thickness evaluated by VSS was (1.72±0.49) mm, and the thickness measured by pathological section was (2.11±0.45) mm. In the hyperplastic scar stage, the thickness measured by 20 MHz ultrasound was (4.11±0.73) mm, the thickness evaluated by VSS was (3.02±0.47) mm, and the thickness measured by pathological section was (4.27±0.44) mm. In the atrophic scar stage, the thickness measured by 20 MHz ultrasound was (1.74±0.64) mm, the thickness measured by VSS was (1.77±0.61) mm, and the thickness measured by pathological section was (1.71±0.67) mm. For scars in the above three periods, there was no statistical significance between scar thickness measured by 20 MHz high-frequency ultrasound and that measured by pathological sections(all P<0.05). In the initial stage of scar formation and hypertrophic stage, the thickness evaluated by VSS was significantly different from that measured by 20 MHz high-frequency ultrasound and pathology (all P<0.05), respectively. (2) Echo intensity was evaluated by ultrasound. In the initial stage of scar formation, the thickness of the epidermis shown by high-frequency ultrasound was close to that of the normal epidermis and presented a high-intensity echo, but there was a strip of echoless or no echo zone of <1 mm between the high-intensity echo epidermis and dermis, which looked like dermal edema. Pathology showed that there were acanthoid changes in the epidermis of the scar at this stage, rich capillaries and a small amount of collagen fibrous tissue in the dermis. In the hyperplastic scar stage, the scar epidermis still showed strong echo, while the dermis showed uneven echo, the superficial dermis showed obvious isoecho, and the deep dermis showed no echo or hypoecho. Pathology showed that the epidermis was thin and smooth, and keratosis was obvious. Collagen fibers parallel to the epidermis could be seen in the superficial layer of the dermis, with regular arrangement. Collagen fibers were increased and thickened in the deep layer of the dermis, in the shape of nodules and swirls. In the atrophic scar stage, the scar epidermis presented a strong echo, and there was no obvious demarcation between the dermis and subcutaneous tissue, presenting a uniform echo. Pathological findings showed that the epidermis became thinner with a "skin nails" -like structure, the junction between the superficial and deep dermis was not obvious, and the collagen fibers were arranged in parallel or oblique direction, and the surface boundary was unclear. Conclusion:20 MHz high-frequency ultrasound is more accurate than VSS in the assessment of thickness of hypertrophic scar, and can reflect the collagen content and moisture ratio in scar. Compared with pathological examination, it has the advantages of non-invasive and fast, and is an effective means to evaluate scar thickness and morphology.

BACKGROUND: Cancer stem-like cells (CSCs) are a small subset of cells in tumors that exhibit self-renewal and differentiation properties. CSCs play a vital role in tumor formation, progression, relapse, and therapeutic resistance. B7-H3, an immunoregulatory protein, has many protumor functions. However, little is known about the mechanism underlying the role of B7-H3 in regulating gastric cancer (GC) stemness. Our study aimed to explore the impacts of B7-H3 on GC stemness and its underlying mechanism. METHODS: GC stemness influenced by B7-H3 was detected both in vitro and in vivo . The expression of stemness-related markers was examined by reverse transcription quantitative polymerase chain reaction, Western blotting, and flow cytometry. Sphere formation assay was used to detect the sphere-forming ability. The underlying regulatory mechanism of B7-H3 on the stemness of GC was investigated by mass spectrometry and subsequent validation experiments. The signaling pathway (Protein kinase B [Akt]/Nuclear factor erythroid 2-related factor 2 [Nrf2] pathway) of B7-H3 on the regulation of glutathione (GSH) metabolism was examined by Western blotting assay. Multi-color immunohistochemistry (mIHC) was used to detect the expression of B7-H3, cluster of differentiation 44 (CD44), and Nrf2 on human GC tissues. Student's t -test was used to compare the difference between two groups. Pearson correlation analysis was used to analyze the relationship between two molecules. The Kaplan-Meier method was used for survival analysis. RESULTS: B7-H3 knockdown suppressed the stemness of GC cells both in vitro and in vivo . Mass spectrometric analysis showed the downregulation of GSH metabolism in short hairpin B7-H3 GC cells, which was further confirmed by the experimental results. Meanwhile, stemness characteristics in B7-H3 overexpressing cells were suppressed after the inhibition of GSH metabolism. Furthermore, Western blotting suggested that B7-H3-induced activation of GSH metabolism occurred through the AKT/Nrf2 pathway, and inhibition of AKT signaling pathway could suppress not only GSH metabolism but also GC stemness. mIHC showed that B7-H3 was highly expressed in GC tissues and was positively correlated with the expression of CD44 and Nrf2. Importantly, GC patients with high expression of B7-H3, CD44, and Nrf2 had worse prognosis ( P = 0.02). CONCLUSIONS B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.
Humans ; Cell Line, Tumor ; Neoplasm Recurrence, Local ; NF-E2-Related Factor 2/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Stomach Neoplasms

Objective To explore the early predictors of the development of the novel coronavirus infection(COVID-19)into severe and critical forms.Methods COVID-19 patients hospitalized in the Department of Intensive Care Medicine,Infection ward,Respiratory and Critical Care Medicine of the First Affiliated Hospital of Guangxi Medical University from December 2022 to March 2023 were selected as the study objects,and were divided into mild/medium group,severe group,and critical group according to the severity of illness during hospitalization.General clinical data and early laboratory results of the three groups were collected and compared.Results A total of 242 patients with novel coronavirus infection were included,including 117 mild/medium patients,55 severe patients,and 70 critically severe patients.There were 165 males and 77 females with a median age of 70(59,80)years.The age,sex,diabetes,heart disease,stroke,combined pneumonia,combined bloodstream infection,APACHE Ⅱ score,respiratory rate on admission,systolic blood pressure,and early white blood cell count(WBC),lymphocyte count(LYM),urea,creatinine,albumin,C-reactive protein,D-dimer,interleukin-6(IL-6),and calcium reduction of patients in the three groups had significant(all P<0.05).Ordered logistic regression shows,previous heart disease,stroke,combined bloodstream infection,WBC,high IL-6 level,and low LYM level were independent risk factors for severe and critical COVID-19 infection[odds ratio(OR)and 95%confidence interval(95%CI)were 3.253(1.694～6.246),5.251(2.378～11.592),respectively.6.920(2.499～19.189),1.111(1.041～1.186),1.003(1.001～1.006),0.571(0.353～0.926)].ROC curve analysis showed that WBC,LYM,IL-6 and their combined detection had certain predictive value for the severity of COVID-19(all P<0.05),and the combined detection of WBC,LYM and IL-6 had better predictive value than a single indicator(P<0.05).Conclusion Previous heart disease,cerebrovascular disease,early combination of bloodstream infection,high levels of IL-6,white blood cell count,and low lymphocyte levels at admission were independent risk factors that helped to predict the severity of COVID-19 infection early.The combined detection of WBC,LYM and IL-6 has certain predictive value for the development of severe and critical COVID-19.

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an important regulator of plasma asymmetric dimethylarginine (ADMA) levels, which are associated with insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD). To elucidate the role of hepatic DDAH1 in the pathogenesis of NAFLD, we used hepatocyte-specific Ddah1-knockout mice (Ddah1^HKO) to examine the progress of high-fat diet (HFD)-induced NAFLD. Compared to diet-matched flox/flox littermates (Ddah1^f/f), Ddah1^HKO mice exhibited higher serum ADMA levels. After HFD feeding for 16 weeks, Ddah1^HKO mice developed more severe liver steatosis and worse insulin resistance than Ddah1^f/f mice. On the contrary, overexpression of DDAH1 attenuated the NAFLD-like phenotype in HFD-fed mice and ob/ob mice. RNA-seq analysis showed that DDAH1 affects NF-κB signaling, lipid metabolic processes, and immune system processes in fatty livers. Furthermore, DDAH1 reduces S100 calcium-binding protein A11 (S100A11) possibly via NF-κB, JNK and oxidative stress-dependent manner in fatty livers. Knockdown of hepatic S100a11 by an AAV8-shS100a11 vector alleviated hepatic steatosis and insulin resistance in HFD-fed Ddah1^HKO mice. In summary, our results suggested that the liver DDAH1/S100A11 axis has a marked effect on liver lipid metabolism in obese mice. Strategies to increase liver DDAH1 activity or decrease S100A11 expression could be a valuable approach for NAFLD therapy.

Objective:To investigate the prognosis and influencing factors in critically ill surgical patients of different feeding intolerance trajectories.Methods:The retrospective cohort study was conducted. The clinical data of 354 critically ill surgical patients who were admitted to 69 medical centers in the Chinese Critical Care Nutrition Trials Group -NEED database from March 2018 to July 2019 were selected. There were 247 males and 107 females, aged 58(46,68)years. According to the trajectory model of feeding intolerance change, 354 patients were divided into 3 categories as feeding intolerance, decreased feeding intolerance, continuous feeding intolerance, including 164, 49, 141 cases respectively. Observation indicators: (1) general situations of patients of different feeding intolerance trajectories; (2) treatment of patients of different feeding intolerance trajectories; (3) survival of patients of different feeding intolerance trajectories; (4) analysis of pro-gnostic factors in critically ill surgical patients. Measurement data of normal distribution were expressed as Mean± SD, and one-way analysis of variance was used for comparison between groups. Measurement data of skewed distribution were expressed as M( Q1, Q3), and Kruskal-Wallis rank sum test was used for comparison between groups. Count data were expressed as absolute numbers or percentages, and chi-square test was used for comparison between groups. Ordinal data were compared using the Kruskal-Wallis rank sum test. Bonferroni correction was used for pairwise comparison. Group-based trajectory model was constructed according to Traj plug-in in Stata17.0 statistical software, and the optimal trajectory model was evaluated by Bayesian information criterion and average posterior probability parameter. The Kaplan-Meier method was used to draw the survival curve and calculate the survival rate, and Log-Rank test was used for survival analyses. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. Results:(1) General situations of patients of different feeding intolerance trajectories. Of 354 critically ill surgical patients, 257 cases underwent enteral nutrition and 97 cases underwent enteral plus parenteral nutrition. The acute physiological and chronic health score (APACHEII) was 17(13,21), and the sequential organ failure score (SOFA) was 6(5,8). The modified Critical Illness Nutritional risk score (mNUTRIC) was 4 (2,5), the number of complications was 2(1,3). There were 293, 55 and 6 patients with grade Ⅰ, grade Ⅱ and grade Ⅲ acute gastrointestinal injury (AGI), and there were 224, 17 and 61 patients who were treated with mechanical ventilation, continuous renal replacement therapy and vasoactive drugs, respectively. The incidence of feeding intolerance in 354 patients increased first and then decreased, reaching a peak of 25.42%(90/354) on the third day and 53.67%(190/354) within 7 days. Of 354 critically ill surgical patients, cases with no feeding intolerance, decreased feeding intolerance, continuous feeding intolerance had the APACHE Ⅱ as 16(12,20), 17(14,25), 18(13,22), mNUTRIC as 3(2,5), 4(3,6), 4(3,5), the number of complications as 2(1,2), 2(2,3), 2(2,3). There were 152, 27, 114 cases with grade Ⅰ AGI, 12, 22, 27 cases with grade Ⅱ-Ⅲ AGI, 95, 39, 90 cases with mechanical ventilation. There were significant differences in the above indicators among the three groups ( H=6.14, 13.11, 28.05, χ2=37.96, 7.65, P< 0.05). Further analysis showed that compared with patients with no feeding intolerance, patients with decreased feeding intolerance and continuous feeding intolerance had the higher number of complications and grade of AGI ( Z=60.32, 54.69, χ2=39.72, 9.52, P<0.05), patients with decreased feeding intolerance had the higher mNUTRIC scores and ratio of mechanical ventilation ( Z=53.41, χ2=7.59, P<0.05). (2) Treatment of patients of different feeding intolerance trajectories. Cases with prokinetic drugs use and post-pyloric feeding were 36, 13 of patients with no feeding intolerance, 25 and 10 of patients with decreased feeding intolerance, 46 and 19 of patients with continuous feeding intolerance, respectively, showing significant differences in the above indicators among the three groups ( χ2=15.76, 6.20, P<0.05). Further analysis showed that compared with patients with no feeding intolerance, patients with decreased feeding intolerance had higher ratio of prokinetic drugs use and ratio of post-pyloric feeding ( χ2=15.60, 6.10, P<0.05). (3) Survival of patients of different feeding intolerance trajectories. The 28-day overall survival rates of patients with no feeding intolerance, decreased feeding intolerance, and continued feeding intolerance were 96.96%, 95.92%, and 87.94%, respectively, showing a significant difference ( χ2=10.39, P<0.05). Further analysis showed a significant difference between patents with no feeding intolerance and patients with continuous feeding intolerance ( χ2=9.19, P<0.05). (4) Analysis of prognostic factors in critically ill surgical patients. Multivariate analysis showed that continuous feeding intolerance was an independent risk factor for 28-day death in critically ill surgical patients ( hazard ratio=3.92, 95% confidence interval as 1.43-10.79, P<0.05). Conclusion:For surgical critically ill patients, patients with continuous feeding intolerance have a higher 28-day mortality than patients with no feeding intolerance, and the continuous feeding intolerance is an independent risk factor for 28-day death in critically ill surgical patients.

Objective:To investigate the role of 20 MHz high-frequency ultrasound in evaluating scar thickness and morphology.Methods:The clinical data of patients with the initial stage of scar formation after burn trauma (<1 month), hypertrophic scar (1-6 months) and atrophic scar (>6 months) treated by the Department of Burn and Cutaneous Surgery, the First Affiliated Hospital of Air Force Medical University from April 2019 to December 2020, were retrospectively analyzed. All patients were evaluated by 20 MHz high-frequency ultrasound, histopathology and Vancouver scar scale (VSS). Three measurement points were randomly selected at the scar during ultrasonic examination, and the average value was recorded as the ultrasonic thickness measurement value. The scar tissue samples were collected from the site of ultrasonic examination, and HE staining and Masson staining were performed. At the same time, scar thickness was evaluated by two physicians using VSS. The difference of scar thickness assessment result among the 3 method in patients at the initial stage of scar formation, hypertrophic scar and atrophic scar was compared. Meanwhile, the relationship between the characteristics of 20 MHz high-frequency ultrasound and histopathology was compared. The measurement data of normal distribution were expressed as Mean±SD. One-way ANOVA was used for comparison among three groups, and SNK- q test was used for pairwise comparison between groups. Counting data were analyzed by Chi-square test. Results:A total of 224 patients were included, including 91 males and 133 females, aged from 1 to 34 years, with an average age of 25.7 years. There were 79 patients at the initial stage of scar formation, 102 at the hypertrophic stage, and 43 at the atrophic stage. (1) In the initial stage of scar formation, the thickness measured by 20 MHz ultrasound was about (2.01±0.68) mm, the thickness evaluated by VSS was (1.72±0.49) mm, and the thickness measured by pathological section was (2.11±0.45) mm. In the hyperplastic scar stage, the thickness measured by 20 MHz ultrasound was (4.11±0.73) mm, the thickness evaluated by VSS was (3.02±0.47) mm, and the thickness measured by pathological section was (4.27±0.44) mm. In the atrophic scar stage, the thickness measured by 20 MHz ultrasound was (1.74±0.64) mm, the thickness measured by VSS was (1.77±0.61) mm, and the thickness measured by pathological section was (1.71±0.67) mm. For scars in the above three periods, there was no statistical significance between scar thickness measured by 20 MHz high-frequency ultrasound and that measured by pathological sections(all P<0.05). In the initial stage of scar formation and hypertrophic stage, the thickness evaluated by VSS was significantly different from that measured by 20 MHz high-frequency ultrasound and pathology (all P<0.05), respectively. (2) Echo intensity was evaluated by ultrasound. In the initial stage of scar formation, the thickness of the epidermis shown by high-frequency ultrasound was close to that of the normal epidermis and presented a high-intensity echo, but there was a strip of echoless or no echo zone of <1 mm between the high-intensity echo epidermis and dermis, which looked like dermal edema. Pathology showed that there were acanthoid changes in the epidermis of the scar at this stage, rich capillaries and a small amount of collagen fibrous tissue in the dermis. In the hyperplastic scar stage, the scar epidermis still showed strong echo, while the dermis showed uneven echo, the superficial dermis showed obvious isoecho, and the deep dermis showed no echo or hypoecho. Pathology showed that the epidermis was thin and smooth, and keratosis was obvious. Collagen fibers parallel to the epidermis could be seen in the superficial layer of the dermis, with regular arrangement. Collagen fibers were increased and thickened in the deep layer of the dermis, in the shape of nodules and swirls. In the atrophic scar stage, the scar epidermis presented a strong echo, and there was no obvious demarcation between the dermis and subcutaneous tissue, presenting a uniform echo. Pathological findings showed that the epidermis became thinner with a "skin nails" -like structure, the junction between the superficial and deep dermis was not obvious, and the collagen fibers were arranged in parallel or oblique direction, and the surface boundary was unclear. Conclusion:20 MHz high-frequency ultrasound is more accurate than VSS in the assessment of thickness of hypertrophic scar, and can reflect the collagen content and moisture ratio in scar. Compared with pathological examination, it has the advantages of non-invasive and fast, and is an effective means to evaluate scar thickness and morphology.

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.
Amyloidogenic Proteins/metabolism* ; Amyotrophic Lateral Sclerosis/genetics* ; Animals ; COVID-19 ; Cytoplasmic Granules/metabolism* ; Mammals ; SARS-CoV-2 ; Stress Granules