Objective To investigate the correlation between the appendicular skeletal mass index(ASMI)and os-teoporosis(OP)in postmenopausal patients with type 2 diabetes(T2DM).Methods 164 hospitalized postmeno-pausal elderly T2DM patients were selected and their bone density(BMD)and appendicular skeletal mass were measured using dual energy X-ray absorption method(DXA).ASMI=appendicular skeletal mass/height2(kg/m2),and they were divided into OP group and non OP group based on T value.The general clinical data,blood biochemical indicators,and ASMI between the two groups were compared,and Logistic regression analysis,ROC curve were further used to analyze the correlation and diagnostic power.Results Compared with non OP group,OP group had a higher incidence of sarcopenia(SAC)(P＜0.05);the differences in age,ASMI,body mass index(BMI),and estradiol(E2)had significant differences between the two groups(P＜0.05);Logistic regression analysis showed that the reduction of ASMI[OR=0.133,95％CI(0.029-0.611)],BMI[OR=0.785,95％CI(0.625-0.985)],and E2[OR=0.967,95％CI(0.942-0.993)]were protective factors for OP;receiver operating curve(ROC)suggested that the AUC of ASMI for OP prediction was 0.752[95％CI(0.632-0.872),P＜0.001]with sensitivity 87.5％,specificity 47.8％,and the best diagnostic value was 5.52 kg/m2.Conclusion The reduction of ASMI,BMI,and E2 is positively correlated with the occurrence of osteoporosis.ASMI is an important protective factor for osteoporosis.Early OP screening and risk factor assessment should be conducted for elderly postmenopausal T2DM patients,and early intervention measures should be taken to reduce the risk of falls and fractures.

Objective To evaluate the clinical efficacy,safety,and potency ratio of microwave ablation(MW A)combined with percutaneous osteoplasty(POP)for the treatment of flat bone metastases.Methods A total of 57 patients with flat bone metastases complicated by intractable pain,who underwent MWA combined with POP(combination therapy)or only POP(pure POP therapy)at the Zhongshan Municipal People's Hospital of China between January 2016 and January 2023,were enrolled in this study.The combination therapy group had 36 patients and the pure POP therapy group had 21 patients.Visual analog scale(VAS),Oswestry Disability Index(ODI),quality of life assessment scale(QOL)were used to evaluate the preoperative and the postoperative different period efficacy,and the results were compared between the two groups.The procedure-related complications in both groups were recorded.Results The technical success rate in the 57 patients was 100％,and no serious postoperative complications occurred.The mean follow-up time was(4.7±1.3)months(range of 3.4-7.2 months).The preoperative and the postoperative one-day,one-week,one-month and 3-month VAS scores in the combination therapy group were(7.39±1.09)points,(6.53±1.17)points,(1.94±0.70)points,(1.11±0.66)points and(1.39±0.59)points respectively,which in the pure POP therapy group were(7.52±1.01)points,(6.81±0.66)points,(3.38±0.65)points,(2.33±0.56)points and(2.52±0.50)points respectively.One week after operation,the VAS scores in the combination therapy group and the pure POP therapy group were decreased by(5.44±1.32)points and(4.14±0.96)points respectively.The differences in the postoperative one-week(t=-7.62,P＜0.01),one-month(t=-7.28,P＜0.01)and 3-month(t=-7.58,P＜0.01)VAS scores between the two groups were statistically significant.The preoperative and the postoperative one-day,one-week,one-month and 3-month ODI scores in the combination therapy group were(44.33±2.91)points,(44.08±2.82)points,(15.92±3.04)points,(14.00±2.39)points and(16.08±3.61)points respectively,which in the pure POP therapy group were(45.67±3.03)points,(45.14±2.80)points,(22.38±3.09)points,(19.76±2.99)points and(22.10±3.10)points respectively.One week after operation,the ODI score in the combination therapy group was decreased by(28.42±4.23)points,which in the pure POP therapy group was decreased by(23.29±4.28)points.The differences in the postoperative one-week(t=-7.50,P＜0.01),one-month(t=-7.37,P＜0.01)and 3-month(t=-6.51,P＜0.01)ODI scores between the two groups were statistically significant.The preoperative and the postoperative one-day,one-week,one-month and 3-month QOL scores in the combination therapy group were(24.69±3.92)points,(26.06±3.05)points,(38.67±3.00)points,(40.25±3.42)points and(39.58±3.99)points respectively,which in the pure POP therapy group were(24.43±3.53)points,(26.76±3.05)points,(32.81±2.17)points,(33.95±2.68)points and(31.19±4.27)points respectively.One week after operation,the QOL score in the combination therapy group was increased by(13.97±4.88)points,which in the pure POP therapy group was increased by(8.38±4.50)points.The differences in the postoperative one-week(t=8.34,P＜0.01),one-month(t=7.56,P＜0.01)and 3-month(t=7.18,P＜0.01)QOL scores between the two groups were statistically significant.The mean operation cost in the combination therapy group was 10 480.43 Chinese yuan,which was higher than that in the pure POP therapy group.Conclusion For the treatment of flat bone metastases,both pure POP therapy and MWA combined with POP therapy are clinically safe and effective,which can significantly relieve pain and improve quality of life.Compared with pure POP therapy,the MWA combined with POP therapy is more effective but its medical cost is more expensive.

Objective:To provide evidence-based recommendations for the prevention and management of lower limb ischemia in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients during treatment according to search, evaluate, and summarize the best evidence on the prevention and management of lower limb ischemia in patients with VA-ECMO.Methods:Based on the PIPOST framework (population, intervention, professional, outcome, setting, and type of evidence), an evidence-based question was formulated. A systematic search was conducted according to the "6S" evidence pyramid model in both domestic and international databases, as well as professional association websites, for all evidence related to the prevention and management of lower limb ischemia in VA-ECMO patients (aged ≥18 years). The types of evidence included clinical decisions, guidelines, expert consensus, systematic reviews, evidence summaries, and original studies. The search was conducted from the construction of the databases to February 2024. Two researchers independently conducted a literature quality evaluation, extracted and summarized evidence from the studies that met the quality criteria.Results:A total of 13 articles were included, consisting of 3 clinical decisions, 3 guidelines, 3 expert consensus, 3 systematic reviews, and 1 randomized controlled trial. A total of 18 pieces of evidence in 7 dimensions were summarized, including risk factors of VA-ECMO lower limb ischemia, evaluation before catheterization, evaluation and monitoring during treatment, prevention of lower limb ischemia, treatment of lower limb ischemia, management of distal perfusion catheter (DPC), and monitoring after VA-ECMO weaning.Conclusion:This evidence summary provides evidence-based recommendations for the prevention and management of lower limb ischemia in VA-ECMO patients, aiming to assist clinical healthcare professionals in developing tailored strategies for the prevention and management of lower limb ischemia based on during VA-ECMO support.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective: : The spontaneous intracerebral hemorrhage (ICH) remains a significant cause of mortality and morbidity throughout the world. The purpose of this retrospective study is to develop multiple models for predicting ICH outcomes using machine learning (ML). Methods: : Between January 2014 and October 2021, we included ICH patients identified by computed tomography or magnetic resonance imaging and treated with surgery. At the 6-month check-up, outcomes were assessed using the modified Rankin Scale. In this study, four ML models, including Support Vector Machine (SVM), Decision Tree C5.0, Artificial Neural Network, Logistic Regression were used to build ICH prediction models. In order to evaluate the reliability and the ML models, we calculated the area under the receiver operating characteristic curve (AUC), specificity, sensitivity, accuracy, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR). Results: : We identified 71 patients who had favorable outcomes and 156 who had unfavorable outcomes. The results showed that the SVM model achieved the best comprehensive prediction efficiency. For the SVM model, the AUC, accuracy, specificity, sensitivity, PLR, NLR, and DOR were 0.91, 0.92, 0.92, 0.93, 11.63, 0.076, and 153.03, respectively. For the SVM model, we found the importance value of time to operating room (TOR) was higher significantly than other variables. Conclusion : The analysis of clinical reliability showed that the SVM model achieved the best comprehensive prediction efficiency and the importance value of TOR was higher significantly than other variables.

Objective:To design and construct a bone nonunion organoid on chip and explore the mechanism of aseptic bone nonunion.Methods:First a semi-open microfluidic chip was designed, on which human bone marrow mesenchymal stromal cells (BMSC), human fetal lung fibroblast 1, (HFL1) and human umbilical vein endothelial cells (HUVEC) were co-cultured, and a three-dimensional organ on chip system was established. Different proportions of HFL1 and HUVEC were co-cultured with BMSC, which were divided into the control group (HFL1∶HUVEC=1∶1), the fibrosis group (HFL1∶HUVEC=3∶1) and the vascularization group (HFL1∶HUVEC=1∶3). The osteogenic differentiation of BMSC was observed by alkaline phosphatase (ALP) and Alizarin red staining. The transcription level of osteogenic marker genes SP7, RUNX2, ALPL, and BGLAP, and vascularization related genes KDR and VWF were analyzed by qPCR. The expression levels of RUNX2 and ALP were determined by Western Blot. Results:In the co-culture system of BMSCs, HFL1, and HUVECs, BMSCs exhibited normal growth and apparent biomineralization behavior. Endothelial cells were capable of forming structured vascular networks, confirming the successful establishment of the system. Compared to the baseline group, the fibrotic group showed no significant decrease in BMSC osteogenic differentiation. The relative expression levels of the mineralization marker genes ALPL and BGLAP were 0.55±0.19 ( P<0.001) and 0.42±0.27 ( P<0.001), respectively. Vascularization genes KDR and VWF were downregulated, with relative expression levels of 0.49±0.17 ( P<0.001) and 0.49±0.21 ( P<0.001). In contrast, in the vascularized group, BMSC osteogenic differentiation genes SP7, RUNX2, ALPL, and BGLAP were upregulated, with relative expression levels of 2.91±0.52 ( P<0.001), 3.83±1.87 ( P<0.001), 3.22±1.29 ( P<0.001), and 5.21±1.46 ( P<0.001), respectively. Vascularization genes KDR and VWF were also upregulated, with relative expressions of 8.24±2.84 ( P<0.001) and 5.32±1.67 ( P<0.001). Western blot results indicated increased expression of RUNX2 and ALP in the vascularized group and decreased expression in the fibrotic group. Conclusion:The bone nonunion organoid on chip could partially simulate the local microenvironment of bone nonunion. Fibrosis may lead to a significant decrease in bone formation ability and vascularization level, which might be an important reason for the occurrence of aseptic bone nonunion.

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation and transcriptional regulation, have been identified through human genetic studies, the East Asian ASD cohorts are still under-represented in genome-wide genetic studies. Here, we applied whole-exome sequencing to 369 ASD trios including probands and unaffected parents of Chinese origin. Using a joint-calling analytical pipeline based on GATK toolkits, we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants, as well as de novo copy number variations containing known ASD-related genes. Importantly, combined with single-cell sequencing data from the developing human brain, we found that the expression of genes with de novo mutations was specifically enriched in the pre-, post-central gyrus (PRC, PC) and banks of the superior temporal (BST) regions in the human brain. By further analyzing the brain imaging data with ASD and healthy controls, we found that the gray volume of the right BST in ASD patients was significantly decreased compared to healthy controls, suggesting the potential structural deficits associated with ASD. Finally, we found a decrease in the seed-based functional connectivity between BST/PC/PRC and sensory areas, the insula, as well as the frontal lobes in ASD patients. This work indicated that combinatorial analysis with genome-wide screening, single-cell sequencing, and brain imaging data reveal the brain regions contributing to the etiology of ASD.
Humans ; Autism Spectrum Disorder/metabolism* ; Autistic Disorder ; Exome Sequencing ; DNA Copy Number Variations ; East Asian People ; Brain/metabolism* ; Mutation/genetics* ; Genetic Predisposition to Disease/genetics*

Prostate cancer remains the second most common malignancy in men worldwide, is a global health issue, and poses a huge health burden. Precision medicine provides more treatment options for prostate cancer patients, but its popularity, drug resistance, and adverse reactions still need to be focused on. Chinese herbal medicines (CHMs) have been widely accepted as an alternative therapy for cancer, with the advantages of multiple targets, multiple pathways, and low toxicity. We searched the experimental research and clinical practice of CHMs for prostate cancer treatment published in PubMed, Embase, and Web of Science in the last five years. We found five CHM formulas and six single CHM extracts as well as 12 CHM-derived compounds, which showed induction of apoptosis, autophagy, and cell cycle arrest, suppression of angiogenesis, proliferation, and migration of prostate cancer cells, reversal of drug resistance, and enhancement of anti-tumor immunity. The mechanisms of action include the PI3K/Akt/mTOR, AR, EGFR and Wnt/β-catenin signaling pathways, which are commonly implicated in the development of prostate cancer. We also summarized the advantages of CHMs in patients with hormone-sensitive and castration-resistant prostate cancer and provided ideas for their further experimental design and application.

【Objective】 To investigate the risk factors and predictive effectiveness of prostate imaging reporting and data system (PI-RADS) score for patients with clinically significant prostate cancer (CsPCa) whose PI-RADS score was 3, so as to provide evidence for the diagnosis and treatment. 【Methods】 The clinical and multi-parameter magnetic resonance imaging (mpMRI) data of 153 CsPCa patients treated during Jan.2017 and Dec.2021 whose PI-RADS score was 3 were retrospectively analyzed. With PI-RADS score of 3 as the independent risk factor for CsPCa, the other relevant independent risk factors in predicting CsPCa were evaluated. 【Results】 Univariate and multivariate analyses showed that prostate-specific antigen (PSA) density and apparent dispersion coefficient (ADC) were independent risk factors for the diagnosis of CsPCa (P<0.05). Analysis of receiver operating characteristic (ROC) curve showed that combined PSA density and ADC were more effective than PSA density and ADC alone (P<0.05). 【Conclusion】 The combination of PSA density and ADC can guide clinicians to identify high-risk CsPCa patients from patients with PI-RADS score of 3 points.

Objective:To analyze measurement results of serum allergen-specific immunoglobulin E (IgE) in patients with eczema/dermatitis.Methods:A retrospective analysis was conducted on serum allergen-specific immunoglobulin E (IgE) levels in 3 051 patients with eczema/dermatitis, who visited the allergy clinic of Huashan Hospital from April 1, 2021 to March 31, 2022. The serum allergen-specific IgE level was detected by using the Phadia allergen detection system, and positive rates of allergens were calculated to determine common inhaled allergens and food allergens in patients with eczema/dermatitis. Comparisons of enumeration data between groups were performed by chi-square test.Results:Among the 3 051 patients with eczema/dermatitis, there were 1 412 with atopic dermatitis and 1 639 were other eczema/dermatitis. Detection of serum allergen-specific IgE showed that 1 629 (53%) patients were positive for allergens, and the number of positive allergen-specific IgEs in each patient was 3.0 ± 1.6. The top 3 common inhaled allergens in patients with eczema/dermatitis were Dermatophagoides farinae (904/1 522, 59%) , Dermatophagoides pteronyssinus (891/1 513, 59%) and Alternaria alternata (206/1 068, 19%) , and the top 3 common food allergens were shrimps (251/1 432, 18%) , egg white (165/992, 17%) and cow milk (149/994, 15%) . Among the 3 051 patients, 25 (1%) were aged < 2 years, 571 (19%) aged 2 - 12 years, 285 (9%) aged 12 - 18 years, and 2 170 (71%) were aged > 18 years. The most common food allergens were both egg white in the age groups of < 2 years and 2 -12 years (77%, 37%, respectively) , and were both shrimps in the age groups of 12 - 18 years and > 18 years (31%, 17%, respectively) . Dermatophagoides pteronyssinus and Dermatophagoides farina were the top 2 common inhaled allergens in all age groups, with the positive rate ranging from 36% to 84%; in addition, the positive rate of molds was relatively high in the age group of 2 - 12 years (mold mixture: 37%; Alternaria alternata: 27%) . From April 2021 to March 2022, the positive rate of outdoor allergens ranged from 10% to 15% among outpatients in every month; the positive rates of tree pollen and grass pollen increased from April 2021, and peaked in October 2021. The patients with atopic dermatitis showed a significantly increased positive rate of allergens (73%) compared with those with other eczema/dermatitis (37%, χ2 = 389.36, P<0.001) , and the rank of common allergens in the patients with atopic dermatitis was basically the same as that in those with eczema/dermatitis. Conclusions:The common allergens were Dermatophagoides farina, Dermatophagoides pteronyssinus and Alternaria alternata in the patients with eczema/dermatitis. Food allergy was more common in infant patients, and inhalation allergy was more common in child, adolescent and adult patients. The positive rate of allergen-specific IgEs was markedly higher in the patients with atopic dermatitis than in those with other eczema/dermatitis.