Infection and inflammation stimulate expansion of a CD74+ Paneth cell subset to regulate disease progression.

Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74+ PCs, whose number correlates with auto or allogeneic inflammatory disease progressions in mice. Similar correlation was found in human inflammatory disease tissues. Infection-stimulated cytokines increase production of reactive oxygen species (ROS) and expression of a PC-specific mucosal pentraxin (Mptx2) in activated PCs. A PC-specific ablation of MyD88 reduced CD74+ PC population, thus ameliorating pathogen-induced systemic disease. A similar phenotype was also observed in mice lacking Mptx2. Thus, infection stimulates expansion of a PC subset that influences disease progression.

TET3-mediated DNA oxidation is essential for intestinal epithelial cell response to stressors.

DNA methylation functions as a repressive epigenetic mark that can be reversed by the Ten-eleven translocation (TET) family of DNA dioxygenases that sequentially oxidize 5-methylcytosine into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC and 5caC can be excised by DNA base-excision repair factors leading to unmodified cytosines. TET enzymes were recently implicated as potential risk factors for inflammatory bowel disease (IBD), but the contribution of TET-mediated DNA oxidation to intestinal homeostasis and response to environmental stressors are unknown. Here, we show prominent roles of TET3 in regulating mouse intestinal epithelial differentiation and response to luminal stressors. Compared with wild-type littermates, mice with intestinal epithelial cell-specific ablation of Tet3 (Tet3ΔIEC) demonstrated a decreased transcriptome involved in innate immune response, Paneth cell differentiation, and epithelial regeneration. Tet3IEC mice exhibited an elevated susceptibility to enteric pathogen infection that is correlated with a decreased epithelial 5hmC abundance. Infection of human enterocytes or mice with the pathogenic bacteria acutely increased 5hmC abundance. Genome-wide 5hmC profiling revealed a shift of genomic enrichment of 5hmC toward genes involved in activating Notch, Wnt, and autophagy pathways. Furthermore, chemical stressor dextran sulfate sodium (DSS) represses epithelial 5hmC abundance in a temporal fashion, and Tet3IEC mice exhibited increased susceptibility to DSS experimental colitis with reduced regenerative capacity. TET3 is a critical regulator of gut epithelial DNA methylome and transcriptome, especially in response to luminal stressors, for the maintenance of tissue homeostasis.

Association Between Triglyceride Glucose Index with Cognitive Impairment and Dementia in Adult Population: A Meta-Analysis.

The current understanding of the correlation between insulin resistance (IR) and cognitive dysfunction is limited. Therefore, the objective of this systematic review and meta-analysis was to assess the association between the triglyceride glucose (TyG) index, a recently suggested indicator of IR, and cognitive impairment and dementia in the adult population. Observational studies pertinent to our research were identified through comprehensive searches of the PubMed, Embase, and Web of Science databases. To account for potential heterogeneity, the random-effects models were employed to aggregate the findings. This meta-analysis included ten observational studies involving 5602409 participants. Compared to those with the low TyG index, subjects with the high TyG index were significantly associated with the risk of cognitive impairment [risk ratio (RR): 1.39, 95% confidence interval (CI): 1.22 to 1.59, p<0.001; I2=45%) and dementia (RR: 1.30, 95% CI: 1.06 to 1.60, p=0.01; I2=50%). The association was consistent for Alzheimer's disease (RR: 1.35, 95% CI: 1.04 to 1.76, p=0.03; I2=54%) and vascular dementia (RR: 1.18, 95% CI: 1.13 to 1.24, p<0.001; I2=0%). Subgroup analyses showed that the association between TyG index with cognitive impairment and dementia were stronger in cross-sectional studies than that in cohort studies (p for subgroup difference=0.02), but not significantly modified by age, sex, or diabetic status of the participants. In conclusion, a high TyG index may be associated with higher risk of cognitive impartment and dementia in adult population.

A machine learning screening model for identifying the risk of high-frequency hearing impairment in a general population.

BACKGROUND: Hearing impairment (HI) has become a major public health issue in China. Currently, due to the limitations of primary health care, the gold standard for HI diagnosis (pure-tone hearing test) is not suitable for large-scale use in community settings. Therefore, the purpose of this study was to develop a cost-effective HI screening model for the general population using machine learning (ML) methods and data gathered from community-based scenarios, aiming to help improve the hearing-related health outcomes of community residents. METHODS: This study recruited 3371 community residents from 7 health centres in Zhejiang, China. Sixty-eight indicators derived from questionnaire surveys and routine haematological tests were delivered and used for modelling. Seven commonly used ML models (the naive Bayes (NB), K-nearest neighbours (KNN), support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGBoost), boosting, and least absolute shrinkage and selection operator (LASSO regression)) were adopted and compared to develop the final high-frequency hearing impairment (HFHI) screening model for community residents. The model was constructed with a nomogram to obtain the risk score of the probability of individuals suffering from HFHI. According to the risk score, the population was divided into three risk stratifications (low, medium and high) and the risk factor characteristics of each dimension under different risk stratifications were identified. RESULTS: Among all the algorithms used, the LASSO-based model achieved the best performance on the validation set by attaining an area under the curve (AUC) of 0.868 (95% confidence interval (CI): 0.847-0.889) and reaching precision, specificity and F-score values all greater than 80%. Five demographic indicators, 7 disease-related features, 5 behavioural factors, 2 environmental exposures, 2 hearing cognitive factors, and 13 blood test indicators were identified in the final screening model. A total of 91.42% (1235/1129) of the subjects in the high-risk group were confirmed to have HI by audiometry, which was 3.99 times greater than that in the low-risk group (22.91%, 301/1314). The high-risk population was mainly characterized as older, low-income and low-educated males, especially those with multiple chronic conditions, noise exposure, poor lifestyle, abnormal blood indices (e.g., red cell distribution width (RDW) and platelet distribution width (PDW)) and liver function indicators (e.g., triglyceride (TG), indirect bilirubin (IBIL), aspartate aminotransferase (AST) and low-density lipoprotein (LDL)). An HFHI nomogram was further generated to improve the operability of the screening model for community applications. CONCLUSIONS: The HFHI risk screening model developed based on ML algorithms can more accurately identify residents with HFHI by categorizing them into the high-risk groups, which can further help to identify modifiable and immutable risk factors for residents at high risk of HI and promote their personalized HI prevention or intervention.

Correction of anterior bowing complicating tibial osteofibrous dysplasia in preadolescents by osteotomy and telescopic nailing without lesional resection: a preliminary study of four-case reports.

BACKGROUND: Osteofibrous dysplasia (OFD) occurs most frequently in the tibia and may result in deformity and pathological fracture. Surgical treatment such as curettage or segment excision has been performed but remains controversial due to high complication rates and surgical burden. This study introduces a new method to manage OFD with anterior bowing of the tibia using minimally invasive tibial osteotomy and telescopic rod (TR) osteosynthesis without extensive lesion resection. METHODS: A retrospective study of 4 children with OFD and tibia bowing deformity treated with minimally invasive tibial wedge osteotomy and TR fixation between January 2015 and November 2020 was performed. Results including bone healing, complications, function based on MSTS score, and recurrance of deformity were assessed. RESULTS: The median follow-up was 29 months. Radiographs showed the median time for union was 3 months. There were no instances of refracture or recurrence of deformity. The mean post-operative MSTS score was significantly higher than preoperative score. CONCLUSIONS: This method avoids large bone defects and reconstructive procedures. It is an effective and minimally invasive approach for managing anterior bowing deformity secondary to OFD while improving function and quality of life. LEVEL OF EVIDENCE: Level IV; Case Series; Treatment Study.

Abnormal coagulation after hepatectomy in patients with normal preoperative coagulation function.

BACKGROUND: To explore the risk factors for postoperative abnormal coagulation (PAC) and establish a predictive model for patients with normal preoperative coagulation function who underwent hepatectomy. MATERIALS AND METHODS: A total of 661 patients with normal preoperative coagulation function who underwent hepatectomy between January 2015 and December 2021 at the First Affiliated Hospital of Sun Yat-sen University were divided into two groups: the postoperative abnormal coagulation group (PAC group, n = 362) and the normal coagulation group (non-PAC group, n = 299). Univariate and multivariate logistic analyses were used to identify the risk factors for PAC. RESULTS: The incidence of PAC in 661 patients who underwent hepatectomy was 54.8% (362/661). The least absolute shrinkage and selection operator (LASSO) method was used for multivariate logistic regression analysis. The preoperative international normalized ratio (INR), intraoperative succinyl gelatin infusion and major hepatectomy were found to be independent risk factors for PAC. A nomogram for predicting the PAC after hepatectomy was constructed. The model presented a receiver operating characteristic (ROC) curve of 0.742 (95% confidence interval (CI): 0.697-0.786) in the training cohort. The validation set demonstrated a promising ROC of 0.711 (95% CI: 0.639-0.783), and the calibration curve closely approximated the true incidence. Decision curve analysis (DCA) was performed to assess the clinical usefulness of the predictive model. The risk of PAC increased when the preoperative international normalized ratio (INR) was greater than 1.025 and the volume of intraoperative succinyl gelatin infusion was greater than 1500 ml. CONCLUSION: The PAC is closely related to the preoperative INR, intraoperative succinyl gelatin infusion and major hepatectomy. A three-factor prediction model was successfully established for predicting the PAC after hepatectomy.

High-flux and bright betatron X-ray source generated from femtosecond laser pulse interaction with sub-critical density plasma.

Recent progress on betatron X-ray source enables the exploration of new physics in fundamental science; however, the application range is still limited by the source flux and brightness. In this Letter, we show the generation of more than 1 × 1012 photons (energy > 1 keV) with a peak brightness of 7.8 × 1022 photons/(s mm2 mrad2) at 0.1% bandwidth (BW) at 10 keV, driven by a femtosecond laser pulse of ≈5.5 J and a sub-critical density plasma (SCDP). The source flux is more than two orders of magnitude higher than that from typical laser wakefield electron acceleration. This method to produce high-flux and bright X-ray source would open a wide range of applications.

Polyene phosphatidylcholine ameliorates synovial inflammation: involvement of PTEN elevation and glycolysis suppression.

BACKGROUND: Synovial inflammation, characterized by the activation of synovial fibroblasts (SFs), is a crucial factor to drive the progression of rheumatoid arthritis (RA). Polyene phosphatidylcholine (PPC), the classic hepatoprotective drug, has been reported to ameliorate arthritis in animals. However, the molecular mechanism remains poorly understood. METHODS AND RESULTS: Using in vitro primary synovial fibroblast (SFs) culture system, we revealed that phosphatase and tension homolog deleted on chromosome 10 (PTEN), a tumor suppressor, mediates the anti-inflammatory effect of PPC in lipopolysaccharide (LPS)-stimulated primary SFs. PPC decreased the production of TNF-α and IL-6 production while elevating the level of IL-10 and TGF-ß. Furthermore, PPC up-regulated the expression of PTEN, but inhibited the expression of p-AKT (ser473) and PI3K-p85α. Moreover, pre-treatment of SF1670 (the inhibitor of PTEN) or 740Y-P (the agonist of AKT/PI3K pathways) partially abrogated the anti-inflammatory effect of PPC. In addition, PPC could inhibit the expression of GLUT4, a key transporter of glucose that fuels the glycolysis, which is accompanied by the expression downregualtion of glycolytic enzymes PFKFB3 and PKM2. Furthermore, PPC could reduce ROS production and mitochondrial membrane potential in LPS-stimulated SFs and MH7A cell line. CONCLUSION: The present study supported that PPC can alleviate synovial inflammation, which involves in the elevation of PTEN and blockage of glycolysis.

Association between the copy number variation of CCSER1 gene and growth traits in Chinese Capra hircus (goat) populations.

Recently, Coiled-coil serine-rich protein 1 (CCSER1) gene is reported to be related to economic traits in livestock, and become a hotspot. In our study, we detected CCSER1 gene CNV in 693 goats from six breeds (GZB, GZW, AN, BH, HG, TH) by quantitative real-time PCR (qPCR) and the association analysis between the types of CNV and growth traits. Then, CCSER1 gene expression pattern was discovered in seven tissues from NB goats. Our results showed that the CCSER1 gene copy numbers were distributed differently in the aforementioned six breeds. The type of CCSER1 gene CNV was significantly associated with body weight and heart girth traits in GZW goat, in which individuals with deletion type were dominant in body weight trait (P < 0.05), while the normal type individuals were more advantageous in heart girth trait (P < 0.01); and there was a significant association with heart girth in TH goat (P < 0.05), which normal type was the dominant one. The expression profile revealed that CCSER1 gene has the highest level in the lung, followed by the small intestine and heart. In conclusion, our result is dedicated to an in-depth study of the novel CCSER1 gene CNV site and to provide essential information for Chinese goats molecular selective breeding in the future.

Younger Age and Left Side Are Risk Factors for Contralateral Trigger Thumb in Children.

BACKGROUND: The metachronism of bilateral trigger thumb (TT) may lead to additional surgery under anesthesia. The aim of this study was to investigate the temporal development of bilateral TT, find risk factors for contralateral TT, and provide evidence for clinical practice. METHODS: A retrospective analysis was performed on children diagnosed with TT in our hospital from January 2016 to December 2019. Age at onset, laterality, sex, the interval time of onset of contralateral symptoms, age at the time of surgery, and preoperative and postoperative follow-up times were collected. The cases were divided into 3 groups: (1) the unilateral group, (2) the simultaneous bilateral group, and (3) the separate bilateral group. RESULTS: A total of 783 patients with 967 TTs were enrolled. There were 599 (76.5%) cases in the unilateral group, 157 (20.1%) cases in the simultaneous bilateral group, and 27 (3.4%) cases in the separate bilateral group. Seven (0.9%) patients underwent additional surgery on the contralateral side under anesthesia. Of these 7 patients, 6 (85.7%) had left-side onset and 5 (71.4%) patients developed bilateral TT by the age of 4. The mean age at the initial onset in the separate bilateral group was 20.1 months, and the mean age at diagnosis of the contralateral thumb was 33.6 months. Binary logistic regression analysis showed that age and side at initial onset had significant differences ( P =0.043 and 0.000, respectively). Receiver operating characteristic curve analysis showed that the cutoff value of age at initial onset was 16 months. CONCLUSIONS: There was a low incidence of metachronous bilateral TT with additional surgery for the contralateral thumb. Age and side at initial onset are risk factors for contralateral TT. LEVEL OF EVIDENCE: Level II; prognostic studies.

Protein Kinase C Is Involved in Vegetative Development, Stress Response and Pathogenicity in Verticillium dahliae.

Potato Verticillium wilt, caused by Verticillium dahliae, is a serious soil-borne vascular disease, which restricts the sustainable development of the potato industry, and the pathogenic mechanism of the fungus is complex. Therefore, it is of great significance to explore the important pathogenic factors of V. dahliae to expand the understanding of its pathology. Protein kinase C (PKC) gene is located in the Ca2+ signaling pathway, which is highly conserved in filamentous fungi and involved in the regulation of a variety of biological processes. In the current study, the PKC gene in V. dahliae (VdPKC) was characterized, and its effects on the fungal pathogenicity and tolerance to fungicide stress were further studied. The results showed that the VdPKC positively regulated the growth and development, conidial germination, and production of V. dahliae, which was necessary for the fungus to achieve pathogenicity. It also affected the formation of melanin and microsclerotia and changed the adaptability of V. dahliae to different environmental stresses. In addition, VdPKC altered the tolerance of V. dahliae to different fungicides, which may be a potential target for polyoxin. Therefore, our results strongly suggest that VdPKC gene is necessary for the vegetative growth, stress response, and pathogenicity of V. dahliae.

Hypothetical Protein VDAG_07742 Is Required for Verticillium dahliae Pathogenicity in Potato.

Verticillium dahliae is a soil-borne pathogenic fungus that causes Verticillium wilt in host plants, a particularly serious problem in potato cultivation. Several pathogenicity-related proteins play important roles in the host infection process, hence, identifying such proteins, especially those with unknown functions, will surely aid in understanding the mechanism responsible for the pathogenesis of the fungus. Here, tandem mass tag (TMT) was used to quantitatively analyze the differentially expressed proteins in V. dahliae during the infection of the susceptible potato cultivar "Favorita". Potato seedlings were infected with V. dahliae and incubated for 36 h, after which 181 proteins were found to be significantly upregulated. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that most of these proteins were involved in early growth and cell wall degradation. The hypothetical, secretory protein with an unknown function, VDAG_07742, was significantly upregulated during infection. The functional analysis with knockout and complementation mutants revealed that the associated gene was not involved in mycelial growth, conidial production, or germination; however, the penetration ability and pathogenicity of VDAG_07742 deletion mutants were significantly reduced. Therefore, our results strongly indicate that VDAG_07742 is essential in the early stage of potato infection by V. dahliae.

New bone formation accelerates during lower limb lengthening and deformity correction in children with Ollier's disease.

BACKGROUND: Ollier's disease can cause severe length discrepancy of the lower extremities and deformity in children. Osteotomy and limb lengthening with external fixation can correct the limb deformity. This study evaluated (1) whether the duration of external fixation was reduced in patients with Ollier's disease, and (2) the incidence of complications such as pin tract infection, external fixation loosening, and joint stiffness. METHODS: Two groups were compared with respect to age, angular correction (AC), lengthening gap (LG), distraction index (DI), lengthening length (LL), lengthening length percentage (L%), lengthening index (LI), bone healing index (BHI), and external fixation index (EFI). Group 1 (Ollier's disease) comprised nine patients undergoing 11 lower limb lengthening procedures using external fixators; group 2 (control, normal lengthened bone) comprised 28 patients undergoing 29 lengthening procedures with external fixators. RESULTS: In patients with Ollier's disease, full correction of the deformity and full restoration of length were achieved in all cases. In the femur, the mean AC (15.97° vs. 6.72°) and DI (1.11 mm/day vs. 0.78 mm/day) were significantly larger, while the LI (9.71 days/cm vs. 13.49 days/cm), BHI (27.00 days/cm vs. 42.09 days/cm), and EFI (37.86 days/cm vs. 56.97 days/cm) were all significantly shorter in group 1 than in group 2 (p < 0.05). In the tibia, the mean AC and L% were larger, while the LG, LI, BHI, and EFI were all shorter in group 1 than in group 2. There was no significant difference between the two groups in the incidence of complications. CONCLUSION: In children with Ollier's disease, new bone formation accelerated and the healing speed of the lengthened segments was faster throughout the whole lengthening period with external fixation, and full correction of the deformity and full restoration of length could be achieved.

Clinical severity prediction in children with osteogenesis imperfecta caused by COL1A1/2 defects.

Osteogenesis imperfecta (OI) is a genetic disease with an estimated prevalence of 1 in 13,500 and 1 in 9700. The classification into subtypes of OI is important for prognosis and management. In this study, we established a clinical severity prediction model depending on multiple features of variants in COL1A1/2 genes. INTRODUCTION: Ninety percent of OI cases are caused by pathogenic variants in the COL1A1/COL1A2 gene. The Sillence classification describes four OI types with variable clinical features ranging from mild symptoms to lethal and progressively deforming symptoms. METHODS: We established a prediction model of the clinical severity of OI based on the random forest model with a training set obtained from the Human Gene Mutation Database, including 790 records of the COL1A1/COL1A2 genes. The features used in the prediction model were respectively based on variant-type features only, and the optimized features. RESULTS: With the training set, the prediction results showed that the area under the receiver operating characteristic curve (AUC) for predicting lethal to severe OI or mild/moderate OI was 0.767 and 0.902, respectively, when using variant-type features only and optimized features for COL1A1 defects, 0.545 and 0.731, respectively, for COL1A2 defects. For the 17 patients from our hospital, prediction accuracy for the patient with the COL1A1 and COL1A2 defects was 76.5% (95% CI: 50.1-93.2%) and 88.2% (95% CI: 63.6-98.5%), respectively. CONCLUSION: We established an OI severity prediction model depending on multiple features of the specific variants in COL1A1/2 genes, with a prediction accuracy of 76-88%. This prediction algorithm is a promising alternative that could prove to be valuable in clinical practice.

Modified Langenskiöld procedure for congenital patella dislocations in pediatric patients.

BACKGROUND: Great difficulty and more failures were the descriptions of the treatment of congenital patella dislocation in pediatric patients. This study aims to evaluate the outcomes of patients with congenital patellar dislocations treated with the modified Langenskiöld procedure. METHODS: The medical records of 16 knees in 11 patients with a diagnosis of congenital patella dislocation were collected from September 2016 to March 2019. They were treated with the modified Langenskiöld procedure. The mean follow-up period was 37.8 months. The outcome measures were the Lysholm score, Kujala score, patellar stability, and knee range of motion. RESULTS: Eleven patients, namely, eight girls and three boys, with 16 knees were enrolled. The mean age at the time of operation was 3.1 years. The post-operative mean Lysholm score was 94.8 (SD 5.1; 87-100), whereas the Kujala score was 95 (SD 5.9; 86-100). There were no recurrent dislocations, and all patients had full extension postoperatively. CONCLUSION: The modified Langenskiöld procedure is a promising solution for the treatment of congenital patella dislocations. LEVEL OF EVIDENCE: Level IV; Case Series; Treatment Study.

Copy number variation of the USP16 gene and its association with milk traits in Chinese Holstein cattle.

Copy number variations (CNVs) were similar to single nucleotide polymorphisms (SNPs) and insertion-deletion (InDel), regarded as genetic variations in many species. CNV is defined as the variable change of DNA segment length compared with the reference genome, including gains or losses from 50 bp to several mega bases. The functions of USP16 gene are diverse, such as regulating the cell cycle, DNA damage, histone H2A deubiquitination or mitotic nuclear division. To analyze the relationship between CNV of USP16 gene and milk traits in Chinese Holstein, we used qPCR to detect the individuals of Chinese Holstein (n = 180). The results showed that the effect of USP16 gene CNV on daily milk yield and fat percentage had significant difference (p < 0.05). The gain was the advantage type in daily milk yield and the loss was the advantage type in fat percentage. Therefore, CNV of USP16 gene is an important factor of milk traits in Chinese Holstein. Meanwhile, it may be used as a molecular marker for assisted selection of milk traits in Chinese Holstein, which provides a theoretical basis for the genetic improvement of cow breeds in China.

DNA methylation status of SERPINA3 gene involved in mRNA expression in three cattle breeds.

DNA methylation could take part in the gene expression and acts an important role in muscle development. In this study, DNA methylation and expression in adipose and muscle tissues were examined at the same time to evaluate the extent of epigenetic modifications and gene expression on the differentially methylated region (DMR) in SERPINA3. Chain reaction of bisulfite sequencing polymerase (BSP) was used to compared difference among DNA methylation patterns. The result of quantitative real-time PCR (qPCR) analysis showed that there was an extensive expression of SERPINA3 gene in tissue and there was a significant difference existing in muscle and adipose between Jiaxian cattle and individual of other breeds with increasing hybridization (p < 0.05). The statistic analyses indicated that DNA methylation patterns had a significant influence to the level of mRNA in tissue of fat and muscle. This study may be an important reference for investigating development of muscle tissue in cattle, and may promote the process of cattle molecular breeding.

Combination Treatment by Cross-Union of the Tibia and Fibula, Autogenic Iliac Bone Grafting, Reliable Fixation and Bone Morphogenetic Proteins for the Treatment of Refractory Congenital Pseudarthrosis of the Tibia.

BACKGROUND: The treatment of congenital pseudarthrosis of the tibia (CPT) remains a challenge because of the difficulties of achieving and maintaining bone union, as well as complications of joint deformity and limb-length discrepancy. The purpose of this study was to evaluate the efficacy of cross-union of the tibia and fibula in achieving union and preventing refracture for patients with refractory CPT as a complementary approach to improve upon conventional surgical treatments. METHODS: A retrospective study including patients with refractory CPT who attended our department between June 2014 and August 2020. Eighteen CPT patients, who had sustained refracture that required cast immobilization or secondary surgery, and were managed by pseudarthrosis resection, cross-union of the tibia and fibula, bone morphogenetic protein-2 and autogenous iliac bone grafting, were included. Clinical outcomes of the bone union rate and the frequency of refracture after performing cross-union of the tibia and fibula were assessed during the follow-up period. RESULTS: The mean follow-up period was 4.3 years (range: 1.5 to 6.25 y). The mean age of the patients at surgery was 5.4 years (range: 2.6 to 10 y), and all 18 (100%) of the 18 patients had final healing at the site of pseudarthrosis. The average time spent to achieve radiologic bone union of the pseudarthrosis after operation was 2.96 months (range: 2.2 to 4.1 mo). Two (11.1%) patients had an average 2.5 cm limb-length discrepancy, none (0%) sustained refracture which needed cast immobilization or secondary surgery. Patients were all pain-free and move actively. CONCLUSIONS: Cross-union of the tibia and fibula is a promising complementary procedure for treating refractory CPT patients. LEVEL OF EVIDENCE: Level IV-case series.

Status of traditional Chinese medicine healthcare services in nursing homes across China.

This study aimed to elucidate the status of traditional Chinese medicine (TCM) healthcare services provided in nursing homes across China. We investigated 484 nursing homes using self-compiled questionnaires with a convenient sampling method. Chi-squared and Wilcoxon rank-sum tests were used for univariate analysis and binary logistic regression for multi-factor analysis. Of the 443 nursing homes finally included, 215 (48.5%) provided TCM healthcare services. Nursing home leaders majored in integrated TCM and Western medicine, leaders with a better understanding of TCM and government policies, nursing homes charging over 5,000 CNY/month, and those with ≥500 beds were more likely to provide improved TCM healthcare services. Massage, moxibustion, cupping or scraping, plaster therapy, decocting pieces, and acupuncture were the most prevalent and popular TCM services. Lack of professionals, financial investment, and policy support were the most common factors limiting the provision of TCM healthcare services in Chinese nursing homes.

Diagnostic and clinical utility of next-generation sequencing in children born with multiple congenital anomalies in the China neonatal genomes project.

Multiple congenital anomalies (MCAs) at birth have emerged as an important cause of neonatal morbidity and mortality. This study aimed to investigate the genetic causes and characteristics of clinical outcomes in a large cohort of neonates with MCAs. Clinical exome sequencing/exome sequencing/genome sequencing were undertaken from December 1, 2016 to December 1, 2019 to detect single nucleotide variations (SNVs) and copy number variations (CNVs) simultaneously in individuals who met the inclusion criteria. A total of 588 neonates with MCAs were enrolled. One hundred sixty-one patients received diagnosis, with 71 CNVs and 90 SNVs detected, the overall diagnostic rate being 27.38%. Cardiovascular malformation was the most common anomaly (60%) and accounted for the top symptomatic proportion in both CNVs and SNVs. As the number of involved system increased from 2 to 3-4, and then to ≥5, the overall diagnostic rate increased gradually from 23.1% to 30.5%, and then to 52.2%, respectively. Patients who received genetic diagnoses were offered better clinical management or were referred to the specific disease clinic. In conclusion, this large cohort study demonstrates that both CNVs and SNVs contribute to the genetic causes of MCAs, and earlier genetic assertion may lead to better clinical management for patients.