Mesenchymal stem cells (MSCs) have been widely used in the treatment of various autoimmune and inflammation-related diseases due to their potent immunomodulatory properties. Several studies have demonstrated that MSC-mediated immunomodulation is complex and bidirectional, with the in vivo microenvironment influencing the direction of this modulation. Indoleamine-2,3-dioxygenase (IDO), an immunosuppressive factor, has been identified as a key "switch" in the immunomodulatory role of MSCs. In this review, we explore how IDO functions as a critical regulator of MSC immunoregulatory plasticity. We delve into the mechanisms by which changes in IDO expression affect the function of various immune cells, summarize relevant research and clinical advances regarding the role of IDO expression in MSC-based therapies for various diseases, and discuss potential therapeutic strategies that target IDO to enhance the stability of MSC therapeutic effects. This provides a theoretical foundation for optimizing MSCs as safer and more effective clinical therapeutic agents.

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry

Objective:To investigate the accuracy, effectiveness and feasibility of MassARRAY genotyping assay in the diagnoses of neonatal genetic metabolic diseases.Methods:This is a retrospective study. From December 2016 to January 2020, newborns were screened by tandem mass spectrometry at the Zhejiang Newborn Screening Center, among which the data of 7 922 suspected positive cases of genetic metabolic diseases were collected. These patients were then tested for the common variants of 27 genetic metabolic diseases by MassARRAY genotyping assay, along with further testing using Sanger or next-generation sequencing used to verify and/or further search for potential variants.Results:A total of 1 408 cases were tested with MassARRAY. Among these, 307 cases were confirmed with certain genetic metabolic diseases. The detection rate of hyperphenylalaninemia was the highest, followed by primary carnitine deficiency, short acyl-coA dehydrogenase deficiency and methylmalonic acidemia. With these cases, the consistency of Sanger sequencing and MassARRAY was 100% (307/307). Another 287 cases were identified as carriers by MassARRAY with a 49.1% (141/287) consistency in reference to Sanger sequencing, mainly involving SLC22A5 and MCCC1 genes. Meanwhile, 50.8% (146/287) of these cases were found to have another variant mainly involving PAH, PTS and ACADS genes. The remaining 814 cases have no variants; 158 cases out of these patients have continuously abnormal amino acids, acyl carnitines, urine organic acid and/or other biochemical indices, and were tested by next-generation sequencing, among which 38% (60/158) were detected with two variants. In this study, a total of 513 patients with genetic metabolic disease were diagnosed, and the detection rate of MassARRAY was 59.8% (307/513). Conclusions:MassARRAY genotyping assay can be used as an early molecular screening method for neonatal genetic metabolic diseases. The detection rate is particularly high in diseases with a high concentration of hotspot variants, such as hyperphenylalaninemia and primary carnitine deficiency. The future application value of MassARRAY should be further improved by continuously optimizing its ability to identify new disease genes and potential variable sites.

OBJECTIVE: To explore effectiveness of positive support reduction and internal fixation in the treatment of femoral neck fractures. METHODS: A clinical data of 74 patients with femoral neck fractures treated with hollow screw internal fixation between September 2017 and September 2021 was retrospectively analyzed. Based on the quality of fracture reduction, they were divided into positive support reduction group (group A, n=25), negative support reduction group (group B, n=21), and anatomical reduction group (group C, n=28). There was no significant difference in baseline data such as gender, age, cause of injury, disease duration, fracture side, Garden classification, and fracture line position classification between groups (P>0.05). The occurrence of complications such as early fixation failure, femoral neck shortening, non-union of fractures, and femoral head necrosis in three groups, as well as the Harris score of the hip joint were recorded and compared. RESULTS: All patients had primary healing of incisions after operation and were followed up more than 12 months. The follow-up time for groups A, B, and C was (21.1±5.7), (22.6±4.3), and (21.9±4.1) months, respectively; there was no significant difference between groups (P>0.05). There was no significant difference in the incidences of non-union of fractures, early internal fixation failure, and the femoral head necrosis between groups (P>0.05). The incidence and length of femoral neck shortening, and the hip Harris score at last follow-up in groups A and C were all superior to those in the group B, with significant difference (P<0.05). There was no significant difference in the above indicators between groups A and C (P>0.05). CONCLUSION Positive support reduction can provide a good biomechanical environment for the healing of femoral neck fractures, thereby achieving a higher fracture healing rate, reducing the occurrence of femoral neck shortening, minimizing the function of hip joint, and achieving effectiveness similar to anatomical reduction.
Humans ; Femur Head Necrosis ; Retrospective Studies ; Femoral Neck Fractures/surgery* ; Femur Neck ; Plastic Surgery Procedures

As main recipient cells for porcine reproductive and respiratory syndrome virus (PRRSV), porcine alveolar macrophage (PAM) are involved in the progress of several highly pathogenic virus infections. However, due to the fact that the PAM cells can only be obtained from primary tissues, research on PAM-based virus-host interactions remains challenging. The improvement of induced pluripotent stem cells (iPSCs) technology provides a new strategy to develop IPSCs-derived PAM cells. Since the CD163 is a macrophage-specific marker and a validated receptor essential for PRRSV infection, generation of stable porcine induced pluripotent stem cells lines containing CD163 reporter system play important roles in the investigation of IPSCs-PAM transition and PAM-based virus-host interaction. Based on the CRISPR/Cas9- mediated gene editing system, we designed a sgRNA targeting CD163 locus and constructed the corresponding donor vectors. To test whether this reporter system has the expected function, the reporter system was introduced into primary PAM cells to detect the expression of RFP. To validate the low effect on stem cell pluripotency, we generated porcine iPSC lines containing CD163 reporter and assessed the pluripotency through multiple assays such as alkaline phosphatase staining, immunofluorescent staining, and EdU staining. The red-fluorescent protein (RFP) expression was detected in CD163-edited PAM cells, suggesting that our reporter system indeed has the ability to reflect the expression of gene CD163. Compared with wild-type (WT) iPSCs, the CD163 reporter-iPSCs display similar pluripotency-associated transcription factors expression. Besides, cells with the reporter system showed consistent cell morphology and proliferation ability as compared to WT iPSCs, indicating that the edited-cells have no effect on stem cell pluripotency. In conclusion, we generated porcine iPSCs that contain a CD163 reporter system. Our results demonstrated that this reporter system was functional and safe. This study provides a platform to investigate the iPS-PAM development and virus-host interaction in PAM cells.
Swine ; Animals ; Induced Pluripotent Stem Cells/metabolism* ; Receptors, Cell Surface/genetics* ; Antigens, CD/metabolism* ; Porcine respiratory and reproductive syndrome virus/genetics*

Objective To investigate the application prospect of the most extensive genome engineering pig internationally in preclinical xenotransplantation. Methods Porcine endogenous retrovirus (PERV) knockout combined with 3 major heterologous antigen gene knockouts and 9 humanized genes for inhibition of complement activation, regulation of coagulation disorders, anti-inflammatory and anti-phagocytosis were transferred into a pig (PERV-KO/3-KO/9-TG) as a donor, and the heart, liver and kidney were obtained and transplanted to 3 Rhesus macaque recipients respectively to establish a preclinical research model of pig-to-Rhesus macaque xenotransplantation. The functional status of xenografts after blood flow reconstruction was observed and the survival of recipients was summarized. The hemodynamics of xenografts were monitored. The change of hematological indexes of each recipient was compared. The histopathological manifestation of xenografts was observed. Results After the blood flow was reconstructed, all xenografts showed ruddy color, soft texture and good perfusion. The transplant heart, liver and kidney showed full arterial and venous blood flow and good perfusion at 1 d after operation. The postoperative survival time of heart, liver, and kidney transplant recipients was 7, 26, and 1 d, respectively. The levels of creatine kinase, creatine kinase isoenzyme, and lactate dehydrogenase increased in heart transplant recipient at 1 d after operation, and gradually recovered to near normal levels at 6 d after operation. All indexes increased sharply at 7 d after operation. The level of aspartate aminotransferase increased in liver transplant recipients at 2 d after operation, and the alanine aminotransferase basically returned to normal at 10 d after operation, but the total bilirubin continued to increase. Both aspartate aminotransferase and alanine aminotransferase increased at 12 d after operation, and reached a peak at 15 d after operation. The kidney transplant recipient developed mild proteinuria at 1 d after operation, and died of sudden severe arrhythmia. Histopathology showed that the tissue structure of cardiac and renal xenografts was close to normal, and liver xenografts presented with patchy necrosis, the liver tissue structure was disordered, accompanied by inflammatory damage, interstitial hemorrhage and thrombotic microangiopathy. Conclusions PERV-KO/3-KO/9-TG pig shows advantages in overcoming hyperacute rejection, mitigating humoral rejection and coagulation dysregulation. However, whether it can be used as potential donor for clinical xenotransplantation needs further evaluation.

Genetic factors are the main causes in occurrence of birth defects. With deep research in the field of genomics and application of molecular biology technology, the carrier status, fetal genetic variation and postpartum screening are respectively detected from pre-pregnancy, pregnancy and post-natal screening (before onset of disease) under perfect three-level prevention and control system for birth defects. Prospective detection, early diagnosis and intervention can prevent the occurrence of birth defects related to genetic diseases at multiple levels. This article describes and analyzes current clinical application and existing challenge of molecular biology techniques in prevention of birth defects related to genetic diseases.

Genetic factors are the main causes in occurrence of birth defects. With deep research in the field of genomics and application of molecular biology technology, the carrier status, fetal genetic variation and postpartum screening are respectively detected from pre-pregnancy, pregnancy and post-natal screening (before onset of disease) under perfect three-level prevention and control system for birth defects. Prospective detection, early diagnosis and intervention can prevent the occurrence of birth defects related to genetic diseases at multiple levels. This article describes and analyzes current clinical application and existing challenge of molecular biology techniques in prevention of birth defects related to genetic diseases.

Medicinal plant Paris L. has high medicinal value. There are 8 varietas of 4 kinds of Sect. Euthya which could be used as Chinese medicine. Sect. Euthya with stout rhizomes are the source of Chinese herb Paris L. and the core source of the medicinal plants in every place of origin. Shaanxi Province is one of the major areas. This paper summarizesand analizes the research progress of Paris L. grew in Shaanxi Province including its medicinal status, effective component, pharmacological, endophytic microorganisms sequencing, resource distribution and utilization, as well as the standardized production and planting and provides suggestions for the further research and rational exploitation and utilization of medicinal plant resources of Paris L. in Shaanxi Province.

Objective:To investigate the application feasibility of Region 4 Stork (R4S) system, an international collaborative newborn screening data platform, combined with cut-off value analysis in the neonatal screening for very long chain acyl-CoA dehydrogenase deficiency (VLCADD) by tandem mass spectrometry (MS/MS).Methods:The retrospective study was performed in 2, 040 072 neonates screened by MS/MS in Neonatal Screening Center of Zhejiang Province, China from October 2013 to July 2018. Nine hundred and ten cases were determined and identified as suspected positive VLCADD neonates by traditional cut-off method of tandem mass spectrometry. The original data of these 910 screened neonates were further analyzed by R4S system. Based on clinical diagnosis and ACADL gene test results, the screening efficiency between two methods was statistically compared.Results:The data of 910 suspected VLCADD-positive cases interpreted by cut-off method were further analyzed by R4S system, and the positive interpretation was reduced to 238 cases (including 9 confirmed positive cases). A total of 16 different mutations were found in ACADL gene sequencing among the confirmed children. The screening false positive rate (FPR) declined from 0.44‰ (901/2 040 072) to 0.11‰ (229/2 040 072), the rate of positive predictive value (PPV) increased from 0.99% (9/910) to 3.78% (9/238), and the specificity increased from 99.96% (2 039 162/2 040 063) to 99.99% (2 039 834/2 040 063). There was a statistically significant difference between cut-off method alone and cut-off method combined R4S system analysis (χ2=393.5, P<0.05). Conclusions:The R4S system combined with cut-off method applied in VLCADD neonatal screening by MS/MS can effectively improve screening performance, reduce false positive rate, and has certain value in clinical application.