BACKGROUND:Scoliosis mainly refers to sequence abnormalities in the coronal,sagittal,and axial positions of the spine,with a Cobb angle of≥10°.The patients may experience symptoms such as unequal shoulder height and back asymmetry.Severe cases may affect the patient's cardiopulmonary function,thereby affecting their daily life.Conservative treatment can control the progression of scoliosis and avoid later surgery.Scoliosis orthosis is currently a commonly used and effective treatment measure in conservative treatment. OBJECTIVE:To summarize and analyze the current research status,hotspots,and trends of scoliosis orthoses both domestically and internationally,providing reference for related research. METHODS:Using bibliometrics and visual analysis as tools,and using a comparison between China and foreign countries as a method,this paper analyzes the literature on scoliosis orthosis journals in the past decade.Based on bibliometrics,the current status of research on scoliosis orthoses is determined.Citespace software is used to analyze key words and identify the current hotspots and future trends in scoliosis orthosis research. RESULTS AND CONCLUSION:(1)At present,the number of literature on scoliosis orthoses is still on a fluctuating upward trend.China and the United States are the main countries for research,with a literature share of over 40%.However,the average citation rate of foreign language literature by Chinese scholars is relatively low.(2)The basic fields of domestic research are mainly surgery and pediatrics,while orthotics and clinical neurology are mainly studied abroad.Among them,there is also a certain number of documents in domestic Chinese medicine,indicating that China is also engaged in the combination of Chinese and Western treatment of scoliosis.The National Natural Science Foundation of China has the highest proportion in the aspect of Chinese and foreign literature,reflecting the importance of the fund attaches to the research of scoliosis orthosis.(3)The authors with the highest number of publications are Qiu Yong and Negrini Stefano,and the most published institutions are the Spinal Surgery Department of Gulou Hospital affiliated to Nanjing University Medical College and UDICE-French Research University.Domestic and foreign authors and institutions have certain communications about this,but not closely,which requires relevant institutions and scholars to further explore and study.(4)From the research hotspots and future trends,the main treatment type is adolescent idiopathic scoliosis,while the production method of the short-column side bending orthosis is three-dimensinoal printing,and the main treatment index is convex progression.The ultimate purpose of treatment is to improve the quality of life of the patients.

Bisphosphonate-related osteonecrosis of jaw(BRONJ)is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells(BMSCs).Corin has recently been demonstrated to act as a key regulator in bone development and orthopedic disorders.However,the role of corin in BRONJ-related BMSCs dysfunction remains unclarified.A m6A epitranscriptomic microarray study from our group shows that the CORIN gene is significantly upregulated and m6A hypermethylated during orofacial BMSCs osteogenic differentiation.Corin knockdown inhibits BMSCs osteogenic differentiation,whereas corin overexpression or soluble corin(sCorin)exerts a promotion effect.Furthermore,corin expression is negatively regulated by bisphosphonates(BPs).Corin overexpression or sCorin reverses BPs-impaired BMSCs differentiation ability.Mechanistically,we find altered expression of phos-ERK in corin knockdown/overexpression BMSCs and BMSCs under sCorin stimulation.PD98059(a selective ERK inhibitor)blocks the corin-mediated promotion effect.With regard to the high methylation level of corin during osteogenic differentiation,we apply a non-selective m6A methylase inhibitor,Cycloleucine,which also blocks the corin-mediated promotion effect.Furthermore,we demonstrate that METTL7A modulates corin m6A modification and reverses BPs-impaired BMSCs function,indicating that METTL7A regulates corin expression and thus contributes to orofacial BMSCs differentiation ability.To conclude,our study reveals that corin reverses BPs-induced BMSCs dysfunction,and METTL7A-mediated corin m6A modification underlies corin promotion of osteogenic differentiation via the ERK pathway.We hope this brings new insights into future clinical treatments for BRONJ.

Objective:To investigate the efficacy and prognosis of CLAG±DAC (Clofarabine, Cytarabine, G-CSF±Decitabine) chemotherapy in patients with relapsed/refractory acute myeloid leukemia (R/R AML) .Methods:Continuous cases of R/R AML treated with the CLAG+DAC protocol or CLAG alone at the First Affiliated Hospital of Soochow University from January 2017 to December 2021 were retrospectively analyzed. The baseline characteristics, individual treatment regimen, treatment effect, disease progression, and survival status of patients were recorded. The factors influencing the efficacy of the CLAG±DAC chemotherapy regimens were analyzed, and the overall survival (OS) time after reinduction was calculated using the Kaplan-Meier method.Results:This study included a total of 53 patients, with 33 male patients and an average age of 40.6 years. Thirty-three patients achieved complete remission (CR+CRi) of the disease after the CLAG±DAC chemotherapy regimen and six patients achieved partial remission (PR), while 14 did not. Thirty-two patients eventually underwent hematopoietic stem cell transplantation, and the median OS of the patients was 55.9 months until follow-up. Patients with disease remission after the application of the CLAG±DAC chemotherapy had a significantly longer survival time than those without remission ( P<0.001). The results of the multifactorial analysis have revealed that combined DAC ( OR=4.60, 95% CI 1.14-23.5, P=0.04) and DNMT3A mutation ( OR=0.14, 95% CI 0.01-0.89, P=0.05) were the factors influencing the efficacy of the CLAG±DAC chemotherapy regimen. The remission rate was relatively higher in patients with R/R AML combined with FLT3-ITD mutation by applying the DAC+CLAG regimen ( OR=10.84, 95% CI 1.48-288.50, P=0.04) . Conclusion:The CLAG±DAC regimen is considered effective in patients with R/R AML, whereas decitabine combined with the CLAG regimen is more suitable for patients with R/R AML combined with FLT3-ITD mutation.

To evaluate the application value of metal clip combined with suture and rubber coil as a simple traction device in endoscopic submucosal dissection (ESD) for intestinal mucosal lesions, a total of 56 patients with early colonic cancer and precancerous lesions who received ESD in Jiangyin People's Hospital from January 2021 to July 2022 were randomly divided into the control group ( n=28, conventional ESD) and the traction group ( n= 28, suture and rubber coil as a simple traction device). The total time of ESD, mucosal dissection time, number of submucosal injections, complete resection rate and complications were compared between the two groups. The operation time of the traction group was shorter than that of the control group (74.64±33.25 min VS 117.18±35.75 min, t=4.61, P<0.001). The desection time of mucosa in the traction group was shorter than that in the control group (51.61±24.87 min VS 99.11±32.73 min, t=6.11, P<0.001). The number of submucosal injection in the traction group was less than that of the control group with significant difference (1.68±1.16 VS 4.96±1.41, t=9.57, P<0.001). There was no significant differences in operation area, complete resection rate or complication between the two groups ( P>0.05). The traction assistance technology of metal clip combined with suture and rubber coil can reduce the technical difficulty of colonic ESD and shorten the operation time.

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Objective:To correlate neoadjuvant radiotherapy and chemotherapy efficacy with changes in peripheral blood T lymphocytes in patients with advanced mid-to-low rectal cancer.Methods:A total of 106 patients with rectal cancer who received treatment in Jinhua Municipal Central Hospital from January 2019 to December 2020 were included in this study. Fasting venous blood was taken before neoadjuvant radiotherapy and chemotherapy and 7 days before surgery to measure the numbers of CD3 +, CD4 +, CD8 +, CD45RA + and CD45RO + cells using flow cytometry. The optimal cut-off point was determined using the receiver operating curve. The influential factors of tumor regression grade were analyzed using logistic regression analysis. Results:After neoadjuvant radiotherapy and chemotherapy, the numbers of CD3 +, CD4 +, CD8 + cells were (401.86 ± 138.65), (225.83 ± 87.17), and (155.84 ± 71.19) respectively, which were significantly decreased compared with before neoadjuvant radiotherapy and chemotherapy [(477.33 ± 141.74), (647.38 ± 203.19), (348.22 ± 113.75), t = 10.78, 11.17, 9.49, all P < 0.05]. There were no significant differences in the percentages of CD3 +, CD4 +, CD8 +, CD45RA + and CD45RO + cells between before and after treatment (all P > 0.05). The percentage of CD45RO + cells was significantly increased after neoadjuvant radiotherapy and chemotherapy. A higher percentage of CD45RO + cells led to a lower tumor regression grade ( P < 0.05). The receiver operating characteristic curve showed that the optimal cut-off point of the percentage of CD45RO + cells was 1.08. The area under the receiver operating characteristic curve was 0.774 ( P = 0.029), with a sensitivity of 82.5% and specificity of 69.6%. The logistic regression analysis revealed that the percentage of CD45RO + cells was significantly correlated with tumor regression grade ( P < 0.05). Conclusion:The percentage of CD45RO + cells in T lymphocyte subsets before and after neoadjuvant radiotherapy and chemotherapy is closely related to tumor regression grade. It can be used as an indicator to predict the sensitivity of neoadjuvant radiotherapy and chemotherapy. This study is of great innovation and science and provides a new idea for clinical practice.

Papillary thyroid carcinoma metastasizing to the kidney are extremely rare events, which may easily be misdiagnosed as renal cell carcinoma. The diagnosis needs to be based on immunohistochemical examination. We described a case of renal tumor to be proved renal metastatic carcinoma from thyroid origin by pathological examination. Computed tomography (CT) scan shows metastasis nodules in lungs. Following total thyroidectomy, he underwent iodine-131 ( 131Ⅰ), thyroid hormone and sorafenib to treat thyroid remnant tumor and metastases. Partial nephrectomy was conducted to remove the left renal metastatic carcinoma for preserving normal renal function. Follow-up revealed that partial pulmonary nodule gradually shrunk, and no new metastasis appeared.

Genetic composition plays critical roles in the pathogenesis of autism spectrum disorder (ASD). Especially, inherited and de novo intronic variants are often seen in patients with ASD. However, the biological significance of intronic variants is difficult to address. Here, among a Chinese ASD cohort, we identified a recurrent inherited intronic variant in the CHD7 gene, which is specifically enriched in East Asian populations. CHD7 has been implicated in numerous developmental disorders including CHARGE syndrome and ASD. To investigate whether the ASD-associated CHD7 intronic variant affects neural development, we established human embryonic stem cells carrying this variant using CRISPR/Cas9 methods and found that the level of CHD7 mRNA significantly decreased compared to control. Upon differentiation towards the forebrain neuronal lineage, we found that neural cells carrying the CHD7 intronic variant exhibited developmental delay and maturity defects. Importantly, we found that TBR1, a gene also implicated in ASD, was significantly increased in neurons carrying the CHD7 intronic variant, suggesting the intrinsic relevance among ASD genes. Furthermore, the morphological defects found in neurons carrying CHD7 intronic mutations were rescued by knocking down TBR1, indicating that TBR1 may be responsible for the defects in CHD7-related disorders. Finally, the CHD7 intronic variant generated three abnormal forms of transcripts through alternative splicing, which all exhibited loss-of-function in functional assays. Our study provides crucial evidence supporting the notion that the intronic variant of CHD7 is potentially an autism susceptibility site, shedding new light on identifying the functions of intronic variants in genetic studies of autism.

Betacoronavirus ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; Single-Cell Analysis

Objective:To analyze the clinical characteristics of patients with different types of coronavirus disease 2019 (COVID-19).Methods:A total of 272 eligible COVID-19 patients who were admitted to Guangzhou Eighth People′s Hospital, Guangzhou Medical University from January 22 to February 15, 2020 were retrospectively enrolled. General characteristics, the first laboratory examination and imaging data of these patients were collected. According to the clinical classification, there were 236 cases in non-severe group (mild+ common type) and 36 cases in severe group (severe+ critical type). Comparisons between groups were performed by t test, chi-square test or rank-sum test when appropriate. Results:There were 23 males and 13 females in the severe group, 103 males and 133 females in the non-severe group, and the difference was statistically significant ( χ2=5.149, P=0.023). The age of severe group was (60.5±11.2) years, which was higher than that of non-severe group (46.8±15.7) years. The difference was statistically significant ( t=6.43, P<0.01). The lymphocyte (LYM) count, platelet (PLT) count and arterial partial pressure of oxygen (PaO 2) in the severe group were 0.90(0.55, 1.10)×10 9/L, 170.00(143.50, 198.00)×10 9/L and 73.50(69.70, 83.00) mmHg(1 mmHg=0.133 kPa), respectively, which were all lower than those in the non-severe group (1.42(1.09, 1.95)×10 9/L, 187.00(148.00, 230.00)×10 9/L and 96.00(83.20, 108.00) mmHg, respectively). The differences were all statistically significant ( Z=5.59, 2.00 and 5.00, respectively, all P<0.05). The levels of creatine kinase (CK), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), C reaction protein (CRP) and procalcitonin (PCT) in the severe group were 123.00(79.00, 212.00) U/L, 32.10(27.00, 47.40) U/L, 305.50(216.00, 396.00) U/L, 37.02(23.92, 63.66) mg/L and 0.09(0.05, 0.19) μg/L, respectively, which were all higher than those in the non-severe group (68.00(48.00, 103.00) U/L, 20.10(16.70, 26.20) U/L, 179.00(150.00, 222.00) U/L, 26.55(18.11, 36.96) mg/L and 0.04(0.03, 0.06) μg/L respectively), and the differences were all statistically significant ( Z=3.89, 5.60, 5.12, 2.85 and 5.43, respectively, all P<0.01). No significant differences were observed in white blood cell count, creatine kinase isoenzyme and blood lactate between the two groups ( Z=1.53, 0.41 and 1.00, respectively, all P>0.05). Conclusion:Gender, age, LYM count, PLT count, PaO 2, CK, AST, LDH, CRP and PCT could be used to provide reference for clinical classification of COVID-19 patients.