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

Bioactive glass(BG)has been used as a candidate for bone and soft tissue repair materials because of its compatibility,bioactivity and ability to form a crystalline hydroxyapatite layer.This paper introduces the mechanism of BG ion release,discusses the application of borosilicate bioactive glass(BBG)in bone and soft tissue repair,and provides an overview of the potential and clinical translational challenges faced by BBG in bone cement,scaffold,hydrogel,and fiber research applications.

Objective To discuss the perioperative care and wound protection of xenotransplantation from genetically edited pigs to monkeys, with the goal of improving the success rate of such experimental procedures. Methods From October 2022 to October 2023, perioperative care and wound protection were performed on 7 recipient rhesus monkeys undergoing xenotransplantation of genetically edited pig tissues and organs. Customized wound protective garments were designed based on monkeys' size and surgical area to protect the wounds, alongside meticulous perioperative care. This included preoperative preparation and medication, intraoperative monitoring of physiological indicators and anesthesia management, and postoperative care comprising wound protection, observation and monitoring, and nutritional support. Results All seven monkeys successfully underwent xenotransplantation. With the aid of protective garments and detailed care, all surgical wounds healed by first intention, and postoperative recovery was satisfactory. Conclusion Proper care and wound protection during xenotransplantation from genetically edited pigs to monkeys not only promote wound healing, but also alleviate pain and harm to animals. This has significant implications for advancing experimental research in pig-monkey xenotransplantation and enhancing animal welfare.

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

Colorectal cancer is one of the most common malignant tumors of digestive tract. In 2020， 1.93 million new cases of colorectal cancer were diagnosed globally， ranking third in the global incidence spectrum， and 930 000 new deaths were reported， ranking second in the global cause of death spectrum. Meanwhile， the medical cost of metastatic colorectal cancer is the highest among all stages. A large number of studies have demonstrated that traditional Chinese medicine（TCM） treatment can bring clinical benefits to patients with metastatic colorectal cancer with unique efficacy. In order to further standardize the TCM diagnosis and treatment for metastatic colorectal cancer and improve the level of TCM diagnosis and treatment， Xiyuan Hospital， China Academy of Chinese Medical Sciences， together with other relevant units in China， according to the guideline development process of the World Health Organization Handbook for Guideline Development and the relevant requirements of the Clinical Evidence Grading Criteria on TCM Based on Evidence Body， the Regulations for Group Standards of China Association of Chinese Medicine and others， combined with the characteristics of TCM diagnosis and treatment and the actual situation in China， the Guidelines for TCM Diagnosis and Treatment of Metastatic Colorectal Cancer was developed in accordance with the Catalogue of TCM Diagnosis and Treatment Plans for 105 Diseases in 24 Specialties issued by Department of Medical Administration of National Administration of TCM.

Gastrointestinal viruses include acute gastroenteritis virus and enterovirus. These viruses are highly contagious and human populations are generally susceptible to them, and the viruses require only tens to hundreds of virus particles to cause infection. Digital polymerase chain reaction (dPCR) has the advantages of high sensitivity, strong anti-interference and direct quantification. It has shown its uniqueness in the detection of gastrointestinal viruses, especially for samples with low viral loads, which is a beneficial supplement to the real-time PCR technology. This article reviews and looks forward to the application of digital PCR technology in gastrointestinal virus detection.

Objective To analyze the changes in morphology of intervertebral foramina in patients with cervical spondylotic radiculopathy (CSR) treated with fixedpoint lateral flexion and rotation manipulation based on three-dimensional (3D) reconstruction technology, so as to provide references for the effectiveness of manipulation treatment. MethodsForty patients with CSR were treated with fixed point lateral flexion and rotation manipulation once every other day for a total of 7 times and 2 weeks as a course of treatment. CT data of the patients before and after treatment were analyzed by using multifunctional CT, Mimics 21.0, Geomagic and SolidWorks 2017. The area of the intervertebral foramen, anterior and posterior diameter of the intervertebral foramen, upper and lower diameter of the intervertebral foramen were measured before and after treatment, as well as the infrared thermal imaging temperature differences of the bilateral neck and shoulder, front and back of the upper limb, and the VAS scores of the patients were observed before treatment, 7 d after treatment, 14 d after treatment and 1 month follow-up. Results Foraminal area, anterior and posterior diameters, upper and lower diameters of 40 patients were improved after treatment, and the temperature differences of infrared thermal imaging of patients before and after treatment were statistically significant. The VAS score of the patients decreased progressively. Conclusions Fixed point lateral flexion manipulation can significantly improve the shape of the intervertebral foramen in patients with CSR, so as to achieve the treatment purpose of relieving nerve compression.

Micro- and mini-bioreactors are characterized by their miniature working volume and comprehensive monitoring of process data, e.g., biomass, pH, dissolved oxygen, and fluorescence that are on par with conventional bench-top systems. The technical advancements of micro- and mini-bioreactors are supported by single-use material and micro-manufacturing, non-invasive optical sensors, automation such as industrial robotics and the integration of design of experiment software with data acquisition and process control. Owing to the miniature scales, micro-bioreactors typically feature lower turbulence intensity and energy dissipation rate, resulting in different mass transfer, mixing and shear conditions as compared to industrial scale equipment. Mini-bioreactors, nevertheless, are closer to large vessels. Micro- and mini-bioreactors are used mostly in screening and process development nowadays, owing to their combined high throughput and richness of data. They are also the hardware that will enable "precision medicine" in the near future.
Biomass ; Bioreactors ; Oxygen

Objective:To investigate the effects of combined exposure of fluorine, arsenic, and fluorine-arsenic on the signaling pathway related protein expression of tumor necrosis factor receptor-related factor 6 (TRAF-6)/nuclear factor κB1(NF-κB1) in a co-culture system of mouse osteoblasts MC3T3-E1 and mouse monocyte macrophage RAW264.7.Methods:MC3T3-E1 cells were co-cultured with RAW264.7 cells after induction with osteogenic inducers. The cells were cultured for 7 days in vitro, and different doses of sodium fluoride (0.0, 0.1, 0.4, 1.6 mmol/L NaF, F), sodium arsenite (0.0, 0.5, 2.5, 12.5 μmol/L NaAsO 2, As) and different doses of fluorine and arsenic were added to the culture medium and cultured for 24 h using factorial design. The expression levels of nuclear factor κB receptor activating factor (RANK), TRAF-6, NF-κB1, T cell activating factor (NFATc1), and tartrate-resistant acid phosphatase (TRAP) protein were detected by Western blotting. Results:When fluorine was used alone, compared with the control group (F 0.0As 0.0, 1.00 ± 0.00), the expressions of RANK, NF-κB1 and TRAP proteins (1.11 ± 0.04, 1.29 ± 0.05, 1.38 ± 0.04, 1.24 ± 0.04, 1.13 ± 0.03, 1.34 ± 0.05, 1.12 ± 0.03, 1.24 ± 0.04, 1.61 ± 0.06) were increased ( P < 0.05); TRAF-6 protein expressions in F 0.1 and F 1.6 groups (1.23 ± 0.04, 1.35 ± 0.03) were increased ( P < 0.05). When arsenic was used alone, compared with the control group (F 0.0As 0.0), the expressions of RANK, TRAF-6, NF-κB1 proteins were increased in As 0.5 group ( P < 0.05), the expressions of RANK and NFATc1 proteins were reduced in As 12.5 group ( P < 0.05). When fluorine was combined with arsenic, at the same dose of fluorine, RANK protein expression in F 0.1As 0.5 group and TRAF-6 protein expression in F 0.1As 12.5, F 0.4As 0.5, F 0.4As 2.5 groups, NF-κB1 protein expression in F 0.1As 0.5 F 0.4As 2.5, F 0.4As 12.5 groups, NFATc1 protein expression in F 0.1As 0.5 and F 0.4As 0.5 groups, TRAP protein expression in F 0.1As 12.5 group were higher than the corresponding fluorine groups alone (F 0.1, F 0.4, P < 0.05), but lower than the sum of fluorine and arsenic alone. At the same dose of arsenic, RANK protein expression in F 0.1As 12.5 group, TRAF-6 protein expression in F 0.1As 12.5 and F 0.4As 2.5 groups, and NF-κB1 protein expression in F 0.1As 12.5, F 0.4As 2.5, F 0.4As 12.5, and F 1.6As 2.5 groups, TRAP protein expression in F 1.6As 2.5 and F 1.6As 12.5 groups were higher than the corresponding arsenic groups alone (As 2.5, As 12.5, P < 0.05), but lower than the sum of fluorine and arsenic alone. Fluorine had a major effect on the expressions of RANK, TRAF-6, NF-κB1, NFATc1, and TRAP proteins ( F=3.41, 341.73, 66.01, 56.49, 147.40, P < 0.05); arsenic also had a main effect on all protein indicators ( F=686.71, 174.96, 107.32, 235.80, 331.37, P < 0.05); the combined effect of fluorine and arsenic had an interaction effect on each protein indicator ( F=50.39, 234.94, 116.72, 67.77, 36.56, P < 0.05). Conclusions:In the co-culture system of MC3T3-E1 and RAW264.7 cells, fluorine can activate TRAF-6-mediated expression of NF-κB1 signaling pathway-related proteins, thereby promoting osteoclast differentiation; the effects of arsenic on the expression of related proteins are not completely consistent. The interaction of fluorine and arsenic exposure on TRAF-6-mediated expression of NF-κB1 signaling pathway-related proteins is mainly antagonistic.

Objective:To study the effects of umbilical cord mesenchymal stem cells (UCMSCs) loaded by graphene oxide (GO) on cartilage repair in two KOA animal models.Methods:30 male New Zealand rabbits aged 12 weeks were randomly divided into A group ( n=15) and B group ( n=15). In the A group, the KOA model was established by the improved Hulth and cartilage defect method, and in the B group, the KOA model was established by the modified papain controlled-release injection method. After the modeling, the rabbits model in each group were divided into 4 subgroups, including blank control group ( n=3), GO group ( n=4), UCMSCs group ( n=4) and GO+UCMSCs group ( n=4). In these subgroups, the rabbit models were respectively treated injected with 0.5 ml of NaCl solution with 9 g/L, GO granular lubricant (GO with 30 μg/ml and solvent with hyaluronic acid with 0.25%), UCMSCs suspension (5×10 6 /ml), and mixed suspension of UCMSCs loaded by GO (GO with 30 μg/ml and UCMSCs with 5×10 6/ml) in right knee joint cavity. The serum levels of NO, collagen type Ⅱ(COL-Ⅱ), glycosaminoglycan (GAG), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). Results:Eight weeks after the treatment, the serum levels of NO, IL-6 and TNF-α in GO+UCMSCs group were lower than those of the blank control group (all P<0.01), and the serum levels of COL-Ⅱ and GAG in GO+UCMSCs group were higher than those of the blank control group (all P<0.01). The serum NO level of the blank control group in group A was lower than that of the blank control group in group B [(22.097±0.352) ng/ml vs (23.662±0.056) ng/ml, P<0.05]. The serum COL-Ⅱ levels of the UCMSCs group and GO+UCMSCs group in group A were higher than those of group B respectively [(15.589±0.063) ng/ml vs (14.429±0.092) ng/ml, and (19.372±0.063) ng/ml vs (16.257±0.416) ng/ml, all P<0.01]. The serum GAG levels of the blank control group and the GO+UCMSCs group in group A were higher than those in group B respectively [(23.832±0.891) ng/ml vs (18.709±0.552) ng/ml, and (37.439±2.155) ng/ml vs (26.554±0.450) ng/ml, all P<0.01). The serum IL-6 levels of the blank control group and the GO+UCMSCs group in group A were lower than those in group B respectively [(16.082±0.323) ng/ml vs (18.367±0.861) ng/ml, P<0.05; (7.426±0.294) ng/ml vs (8.680±0.242) ng/ml, P<0.01]. The serum TNF-α levels of the blank control group and the GO+UCMSCs group in group A were lower than those in group B respectively [(9.466±0.177) ng/ml vs (10.013±0.197) ng/ml, P<0.05; (5.139±0.183) ng/ml vs (6.210±0.058) ng/ml, P<0.01]. Conclusions:GO loaded UCMSCs can promote the secretion of chondrocytes in rabbit KOA models, reduce inflammatory levels in joints, and play a role in cartilage repair.