Single-nucleus RNA and multiomics in situ pairwise sequencing reveals cellular heterogeneity of the abnormal ligamentum teres in patients with developmental dysplasia of the hip.

Developmental dysplasia of the hip (DDH) is the most common hip deformity in pediatric orthopedics. One of the common pathological changes in DDH is the thickening and hypertrophy of the ligamentum teres. However, the underlying pathogenic mechanism responsible for these changes remains unclear. This study represents the first time that the heterogeneity of cell subsets in the abnormal ligamentum teres of patients with DDH has been resolved at the single-cell and spatial levels by snRNA-Seq and MiP-Seq. Through gene set enrichment and intercellular communication network analyses, we found that receptor-like cells and ligament stem cells may play an essential role in the pathological changes resulting in ligamentum teres thickening and hypertrophy. Eight ligand-receptor pairs related to the ECM-receptor pathway were observed to be closely associated with DDH. Further, using the Monocle R package, we predicted a differentiation trajectory of pericytes into two branches, leading to junctional ligament stem cells or fibroblasts. The expression of extracellular matrix-related genes along pseudotemporal trajectories was also investigated. Using MiP-Seq, we determined the expression distribution of marker genes specific to different cell types within the ligamentum teres, as well as differentially expressed DDH-associated genes at the spatial level.

Experience with the management of 2599 cases of congenital muscular torticollis and a multicenter epidemiological investigation in 17 hospitals in China.

BACKGROUND: Congenital muscular torticollis (CMT) is a common musculoskeletal disease affecting infants and young children. If CMT is not treated correctly and timely, it can lead to limited head and neck movements, head and neck deviation, and abnormal posture. In order to improve patients' symptoms and alleviate the negative impact of the disease on their lives, we are committed to exploring the treatment of CMT. METHODS: The general clinical and ultrasonographic data of 2599 children with CMT who received standardized treatment at Shenzhen Children's Hospital from 2004 to 2020 were retrospectively reviewed. According to given treatment, children with CMT were divided into the physiotherapy group, physiotherapy combined with glucocorticoid treatment group, and surgical treatment group. We divided children with CMT into local mass, uniform thickening, and atrophy according to ultrasound features. General clinical information, treatment, and ultrasound examination data in each group were compared. Additionally, electronic medical records of 2344 patients admitted due to CMT in 17 tertiary children's hospitals of China's Futang Research Center of Pediatric Development (FRCPD) from 2015 to 2019 were retrospectively analyzed. Data on sex, age, year of admission and discharge, and treatment costs during hospitalization were extracted from the first medical record pages according to the ICD codes. The data were assessed for normality using the Kolmogorov-Smirnov test. Depending on the data distribution, they were analyzed using parametric tests, such as the t-test, or non-parametric tests. Qualitative data are expressed as percentages (%) and analyzed using the chi-square or Fisher's exact probability test, with α = 0.05 as the test level. P < 0.05 was considered to be indicative of a statistically significant difference. RESULTS: Three types of CMT were defined based on sternocleidomastoid muscle ultrasound examination characteristics: local mass, uniform thickening, and atrophy. Age at first diagnosis was 69.21 ± 108.41 days in local mass type group, 216.85 ± 324.09 days in uniform thickening group, and 417.88 ± 739.05 days in atrophy- type group; while age at first physiotherapy use was 94.06 ± 206.49 days, 255.00 ± 430.62 days, 540.92 ± 1059.29 respectively. The children included in local mass type group have shown a high success rate of conservative treatment, with a rate of 7.5% of children underwent surgery. Age at first diagnosis was 112.44 ± 224.12 days in the physiotherapy group, 115.87 ± 144.86 days in the physiotherapy combined with glucocorticoid treatment subgroup, whereas the age at first physiotherapy use was 137.38 ± 312.11 and 196.91 ± 344.26 days respectively. In the observation period (2015-2019) the mean age at surgery for CMT in 17 tertiary children's hospitals of the FRCPD was 50 months. Overall, 663 children with CMT were 1-2 years of age, accounting for the largest proportion (28.3%). Followed by 417 individuals (17.8%) were 7-14 years of age, indicating that there are still more children with CMT receiving surgical treatment later. CONCLUSIONS: Early diagnosis and treatment are essential to improve the conservative treatment success rate and achieve good prognosis in children with CMT. Our team's concept for treating CMT is as follows: after diagnosing the children, we will adopt the standardized protocol of treatment, with physiotherapy combined with the injection of glucocorticoid drugs and SCM release surgery, when needed. This program has a high conservative treatment success rate and may facilitate the achievement of better prognosis and reduced teratogenicity rate.

Clinical characteristics of 1124 children with epiphyseal fractures.

BACKGROUND: In this study, to provide a theoretical basis for understanding the clinical characteristics of epiphyseal fractures in children and improving their management, we explored and analyzed the proportions of different types of epiphyseal fractures in children and evaluated the causes of injury and epidemiological characteristics. METHODS: We retrospectively analyzed children younger than 18 years with fresh epiphyseal fractures who were admitted to our hospital from July 2015 to February 2020. Demographic information, injury mechanisms, fracture characteristics, fracture classification and surgical information were collected. RESULTS: A total of 1124 pediatric patients (1147 epiphyseal fractures), including 789 boys and 335 girls, were included in this study. Epiphyseal fractures were classified as Salter-Harris type II (1002 cases), type IV (105 cases), type III (25 cases), Salter-Harris type I (14 cases), and Salter-Harris type V (1 case). The number of fracture sites peaked in the adolescent group (440 cases). The most three common sites of epiphyseal fractures were the distal radius (460 cases) in which Salter-Harris type II fractures were the most common (454 cases) and Salter-Harris type I (3 cases), Salter-Harris type IV (2 cases), Salter-Harris type III was the least common (1 case). Followed by phalanges of fingers (233 cases) in which Salter-Harris type II fractures were the most common (224 cases) and Salter-Harris type IV (4 cases), Salter-Harris type I (3 cases), Salter-Harris type III fractures were the least common (2 cases). Distal humerus (146 cases) in which Salter-Harris type II fractures were the most common (95 cases), followed by Salter-Harris type IV (49 cases), Salter-Harris type I fractures were the least common (2 cases). The most three important causes of fractures were falls (720 patients), car accident injuries (68 patients), and basketball falls (43 patients). Among the 1124 children with epiphyseal fractures, 1058 were treated mainly by surgery and the ratio of open and closed reduction was 1:5.3. Eighty-eight patients showed an interval > 72 h between the injury and the hospital visit. Among these 88 patients, the most common fracture type was distal radial epiphyseal fracture (32 cases), and all fractures were of Salter-Harris type II. CONCLUSIONS: The epidemiological characteristics of epiphyseal fractures in children indicate the need to strengthen health and safety education and protective measures to prevent the occurrence of these fractures in children. In addition, emergency surgeons and orthopedic surgeons in general hospitals should strengthen their basic knowledge of diagnosing and treating epiphyseal injuries in children to reduce missed diagnoses, misdiagnoses or malpractice.

Pyrotinib combining with radiotherapy on breast cancer with brain metastasis.

With the extensive application of anti-human epidermal growth factor receptor-2 (HER2) targeted therapy, the prognosis of HER2-positive breast cancer brain metastasis (BCBM) has been improved greatly. Due to the lack of prospective randomized controlled studies; however, the treatment of active brain metastasis (BM) remains a difficulty in clinic. Based upon the retrospective studies, an effective approach of radiotherapy combined with pyrotinib in HER2-positive BCBM treatment was investigated in present research. In all, 29 patients who had active BM in HER2-positive breast cancer (BC) and underwent whole-brain radiotherapy (WBRT) combined with pyrotinib from January 2019 to May 2021 were enrolled. The progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR), objective response rate (ORR), and drug-related adverse events (AEs) were analyzed among patients undergoing WBRT combined with concurrent or sequence pyrotinib + capecitabine. After the systematic treatments using WBRT combined with pyrotinib + capecitabine, the mPFS and mOS of BM patients were 6.5 months and 15.5 months, respectively. PFS (7.2 vs 6.2 months, p = 0.038) and OS (19.0 vs 14.0 months, p = 0.014) were longer after sequence treatments than those after concurrent treatment. The central nervous system (CNS) ORR of sequence treatment was superior to that of concurrent treatment (80.4% vs 58.6%, p < 0.05). Vomiting (17.2%) and diarrhea (10.3%) were the most common adverse reactions ⩾ grade 3. WBRT combined with pyrotinib is safe and effective for the treatments of active BM in HER2-positive BC. WBRT combined with sequence pyrotinib + capecitabine is more effective and less toxic than concurrent treatment. Therefore, sequence treatment is potentially a preferred regimen for patients with active BM in HER2-positive BC. The size and number of BM lesions, presence or absence of hepatic metastasis, and combination mode of radiotherapy and targeted therapy are independent risk factors for active BM prognosis.

Pyrotinib for Elderly Patients with Advanced HER2-Positive Breast Cancer.

Introduction: According to the latest global cancer data released by WHO in 2020, the incidence of breast cancer (BC) has been the most prevalent, and the mortality rate of female malignant tumor ranks the first. Methods: To evaluate toxicity and efficacy regarding oral Pyrotinib for elderly patients with advanced HER2-positive breast cancer (BC) in Xinjiang, 45 elderly patients having advanced HER2-positive BC with age ≥65 years and receiving Pyrotinib-based combined therapy from January 2019 to May 2021 in Xinjiang were enrolled in this study. PFS, CBR, ORR and drug-related adverse events (AE) of oral Pyrotinib in the patients were retrospectively analyzed. All 45 patients completed the efficacy evaluation. Results: Total ORR and CBR of the whole group was 37.8% and 77.8%, respectively. There were 14 patients with brain metastases (31.1%), with a median PFS of 6.8 months (95% CI: 5.4~9.8). In terms of the number of treatment lines, mPFS for line 1-2 was 8.3 months (95% CI: 6.3~11.4), and mPFS for line ≥3 was 3.3 months (95% CI: 2.7~5.1). At the final maintenance dose, mPFS at standard doses of 400mg, 320mg and 240mg were 9.1 months (95% CI: 4.1~9.5), 8.3 months (95% CI: 4.3~12.2) and 4.8 months (95% CI: 2.1~7.5), respectively. Discussion: Applying Pyrotinib in elderly patients, the main adverse reaction was diarrhea, accounting for 88.9% (40/45). Pyrotinib is safe and effective for elderly patients with advanced HER2 positive BC.

Pyrotinib-based treatments in HER2-positive breast cancer patients with brain metastases.

OBJECTIVES: Extensive application of anti-HER2 targeted therapy improves significantly the HER2-positive advanced breast cancer (BC) prognosis, however, it is still difficult to treat brain metastasis. In current study, we explored effective approaches via combining pyrotinib to treat brain metastasis in patients with HER2-positive advanced BC based upon clinical data. MATERIALS AND METHODS: Current study included 61 HER2-positive BC patients with brain metastases (BM) who were treated by pyrotinib-based regimens. The systemic regimens included pyrotinib combined with capecitabine, pyrotinib combined with nab-paclitaxel, and pyrotinib combined with vinorelbine. Patients' progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR) and objective response rate (ORR), as well as drug-related adverse events (AEs) in regard of each combination regimen were analyzed. RESULTS: Pyrotinib-based systemic therapy resulted in 8.6 months median PFS (mPFS) and 18.0 months median OS (mOS) among the BM patients. Regarding different regimens, the combination of pyrotinib with nab-paclitaxel was superior to the combination with capecitabine and vinorelbine with respect to PFS and OS. The central nervous system (CNS) ORR did not showcase significant difference among 3 regimens, however, nab-paclitaxel combined regimen obtained the best peripheral ORR (84.6%) (p ≤ .05). CONCLUSIONS: Pyrotinib-based combination therapy is safe for HER2-positive brain metastasis treatment. Compared with vinorelbine or capecitabine, pyrotinib combined with nab-paclitaxel is more effective with less toxicity, which is the preferable regimen for HER2-positive brain metastasis.KEY MESSAGESPresent investigation investigated effective methods through combining pyrotinib to treat brain metastasis with HER2-positive advanced brain cancer. The outcomes verified that pyrotinib-based combination therapy was safe and efficient to treat HER2-positive brain metastasis. Therefore, it is effective to treat brain metastasis applying anti-HER2 targeted therapies although pyrotinib showcases efficiency regarding its treatments for the metastasis.

Screening for musculoskeletal system malformations and birth injuries in newborns: Results of a screening program in two hospitals in Shenzen, China.

Importance: There are a variety of musculoskeletal malformations and injuries that can occur in newborns. These can be a significant cause of perinatal death or a reason for miscarriage and can lead to long-term functional issues if not managed appropriately. There is no systematic and well-established screening program for neonatal musculoskeletal malformations and injuries in China now. Objective: To report the incidence and types of congenital musculoskeletal malformations in two hospitals in Shenzhen City, to explore and discuss the details of the screening procedure and improve future prevention and treatment. Methods: From October 2013 to May 2014, 2564 one-day-old newborns were screened by a pediatric orthopedic physical examination, in combination with ultrasonography when required, and the incidence and variety of diseases were recorded statistically. Results: Among 2564 screened newborns, the following musculoskeletal conditions were identified: congenital muscular torticollis (CMT) (seven cases, 0.27%), hip subluxation (four cases, 0.16%), hip dysplasia (47 cases, 1.83%), congenital talipes equinovarus (CTEV) (two cases, 0.08%), congenital talipes calcaneovalgus (15 cases, 0.58%), polydactyly (nine cases, 0.35%), syndactyly (one case, 0.04%), and spinal hemivertebra (one case, 0.04%). Additionally, there were five (0.19%) neonates with birth injuries. Interpretation: It is feasible to carry out neonatal screening and identification of musculoskeletal malformations and birth injuries in China. This is helpful as timely detection and early intervention for many of these conditions can avoid permanent functional impairment in these children.

Factors influencing and long-term effects of manual myotomy phenomenon during physiotherapy for congenital muscular torticollis.

PURPOSE: To investigate the factors influencing and long-term effects of manual myotomy (MM) occurring during physiotherapy for congenital muscular torticollis (CMT). METHODS: We retrospectively collected the clinical data of children with CMT receiving physiotherapy between 2008 and 2018. The children were divided into manual myotomy (MM) and non-manual myotomy (NMM) groups according to whether MM occurred during treatment. We assessed physiotherapy outcomes in children with CMT using craniofacial asymmetry parameters and the Cheng-Tang rating score. By measuring the ear-eye distance, ear-nose distance, eye-mouth distance, ear-mouth distance, half-head circumference, and half-head top at two sides to evaluate craniofacial asymmetry. Based on the Cheng-Tang assessment criteria, we recorded the range of rotation, range of lateral flexion, the status of the contracted muscle, the hardness of the mass, the extent of head tilting during activities and sleeping, the status of daily activities, face size, type of head shape, cranial changes, and subjective head tilting to assess the effectiveness of treatment. Clinical data and outcome indicators (craniofacial asymmetry parameters and Cheng-Tang rating score) were compared. RESULTS: The MM group had a significantly higher total Cheng-Tang rating score than the NMM group (P < 0.05). Age at initial physiotherapy session was the risk factor for MM during physiotherapy. CONCLUSION: Children with CMT developing MM during physiotherapy generally have a good outcome, although we do not recommend MM as a goal of treatment. Physiotherapists should understand this phenomenon, assess relevant factors to predict risk, and carefully observe treatment to prevent possible complications.

Upper limb pediatric fractures in 22 tertiary children's hospitals, China: a multicenter epidemiological investigation and economic factor analysis of 32,832 hospitalized children.

BACKGROUND: Fractures are the most common type of unintentional injury in children, with traumatic upper limb fractures accounting for approximately 80% of all childhood fractures. Many epidemiological investigations of upper limb fractures in children have been conducted, but with the development of society, the patterns of childhood fractures may have changed. This study aimed to analyze the epidemiology and economic cost factors of upper limb fractures in Chinese children. METHODS: We retrospectively reviewed children with upper limb fractures or old upper limb fractures hospitalized between December 1, 2015, and December 31, 2019, in 22 tertiary children's hospitals, under China's Futang Research Center of Pediatric Development. We used the ICD10 codes on the front sheet of their medical records to identify cases and extracted data on age, sex, injury cause, fracture site, treatment, the year of admission and discharge, visiting time, and various costs during hospitalization from the medical record. RESULTS: A total of 32,439 children (21,478 boys and 10,961 girls) were identified, of whom 32,080 had fresh fractures and 359 had old fractures. The peak age was 3-6 years in both sexes. A total of 4788 were infants, 14,320 were preschoolers, 10,499 were in of primary school age, and 2832 were adolescent. Fractures were most frequent in autumn (August to October). Admissions peaked at 0 o'clock. Among the 32,080 children with fresh upper limb fractures, the most common fracture site was the distal humerus, with a total of 20,090 fracture events including 13,134 humeral supracondylar fractures and 4914 lateral humeral condyle fractures. The most common cause of injuries was falling over. The most common joint dislocation accompanying upper limb fractures occurred in the elbow, involving 254 cases. Surgery was performed in 31,274 children, and 806 did not receive surgery. Among those with clear operative records, 10,962 children were treated with open reduction and 18,066 with closed reduction. The number of cases was largest in the East China region (Anhui Province, Shandong Province, Jiangsu Province, Zhejiang Province, and Fujian Province), with 12,065 cases overall. Among the 359 children with old fractures, 118 were admitted with a diagnosis of "old humerus fracture," accounting for the highest proportion; 244 underwent surgical open reduction, 16.16% of whom had osteotomy. For the children with fresh fractures, the average total hospital cost was 10,994 yuan, and the highest average total hospital cost was 14,053 yuan, for humeral shaft fractures. For the children with old fractures, the average total hospital cost was 15,151 yuan, and the highest average total hospital cost was 20,698 yuan, for old ulna fractures. Cost of materials was the principle factor affecting total hospital cost, followed by surgery and anesthesia costs, both in children with fresh fractures and those with old fractures. Significant differences were observed in all hospital costs (P < 0.001) except treatment costs (P = 0.702), between children with fresh fractures and those with old fractures. Among the 32,439 children, full self-payment accounted for the highest proportion of all payment methods, involving 17,088 cases, with an average cost of 11,111 yuan. CONCLUSION: Information on the epidemiological characteristics of childhood fractures suggests that health and safety education and protective measures should be strengthened to prevent upper limb fractures in children. For both fresh and old fractures, the cost of materials was the principal factor affecting total hospital cost, followed by surgery and anesthesia costs. The overall average total hospital cost is higher in children with old fractures than in children with fresh fractures. Among all children, full self-payment, at 53% of children, accounted for the highest proportion of all payment methods. Hospital costs are a headache for those families who will pay on their own. It can lead to a delayed treatment and unhealed fractures or malunion in some children. Therefore, the child trauma care system and training on fractures need to be improved, to reduce the late presentation of fractures. These combined measures will improve children's quality of life, reduce the expenditure of families, and decrease the public health burden. To provide better medical services for children, authorities must improve the allocation of health resources, establish a comprehensive medical security system for children, and set up more child trauma centers.

Pillar[5]arene-Based Dual Chiral Organoboranes with Allowed Host-Guest Chemistry and Circularly Polarized Luminescence.

We first describe two examples of highly luminescent organoboranes (NP5BN1 and NP5BN2) with dual chirality that were achieved by molecular functionalization of planar chiral pillar[5]arenes with naphthyls. Sufficiently strong steric effects are imposed by triarylamine (Ar3N) and triarylborane (Ar3B) moieties and further enhanced by the proximity of the chiral building blocks, leading to the isolation of multiple enantiomers via chiral high-performance liquid chromatography. The intramolecular charge transfer from N-donor to B-acceptor across both chiral subunits enabled the circularly polarized luminescence and thermally robust colorimetric responses in their emissions. Furthermore, their remarkable host-guest chemistry was allowed at no expense in the pursuit of advanced chiroptical properties using pillar[5]arene-based supramolecular scaffolds.

Clinical relevance of multi-drug resistance gene C3435T polymorphism in diffuse large B-cell lymphoma in Xinjiang.

To explore the relationship between C3435T polymorphism of multi-drug resistance gene (MDR1) gene and susceptibility, clinicopathological characteristics, curative effect and hematological toxicity of diffuse large B-cell lymphoma (DLBCL) in XinJiang.The peripheral venous blood samples of 54 patients with DLBCL and 60 healthy controls were collected. The alleles and genotypes of MDR1 gene C3435T were detected by DNA direct extraction with PCR technique, and the frequency of C3435T allele and genotypes were detected by the chi-square test. The relationship between the allele and genotype distribution of C3435T locus and the susceptibility, clinicopathological characteristics, curative effect and hematological toxicity of DLBCL were analyzed.1 the frequency of CT heterozygote and CC homozygote mutation was significantly higher in the case group (46.3% in CT genotype and 42.6% in CC genotype) compared to the control group (P < 0.05). The frequency of CC genotype mutation in the case group was 42.6%, which was significantly higher than that in the control group (P < 0.05, OR 3.209, 95% CI: 1.288-7.997). 2 the genotypes of C3435T locus of MDR1 gene were distributed in age, sex, nationality, pathological characteristics, clinical-stage, IPI index, B symptoms, infection with EB virus, clinicopathological characteristics and clinical efficacy of hepatitis B in patients with DLBCL. There was no significant difference in myelosuppression (P > 0.05).The homozygous mutation genotype of CC is the risk genotype of DLBCL. The alleles and genotypes are not associated with the clinicopathological characteristics, efficacy and myelosuppression toxicity of DLBCL.

[Synthesis of pyrroloquinoline quinone by recombinant Gluconobacter oxydans].

Pyrroloquinoline quinone (PQQ), an important redox enzyme cofactor, has many physiological and biochemical functions, and is widely used in food, medicine, health and agriculture industry. In this study, PQQ production by recombinant Gluconobacter oxydans was investigated. First, to reduce the by-product of acetic acid, the recombinant strain G. oxydans T1 was constructed, in which the pyruvate decarboxylase (GOX1081) was knocked out. Then the pqqABCDE gene cluster and tldD gene were fused under the control of endogenous constitutive promoter P0169, to generate the recombinant strain G. oxydans T2. Finally, the medium composition and fermentation conditions were optimized. The biomass of G. oxydans T1 and G. oxydans T2 were increased by 43.02% and 38.76% respectively, and the PQQ production was 4.82 and 20.5 times higher than that of the wild strain, respectively. Furthermore, the carbon sources and culture conditions of G. oxydans T2 were optimized, resulting in a final PQQ yield of (51.32±0.899 7 mg/L), 345.6 times higher than that of the wild strain. In all, the biomass of G. oxydans and the yield of PQQ can be effectively increased by genetic engineering.

Triarylboron/Triarylamine-Functionalized 2,2'-Bipyridine Ligands and Their Copper(I) Complexes.

We report herein three new either -BMes2 (Mes = mesityl) or -NPh2 group-functionalized 2,2'-bipyridine ligands-4,4'-(p-BMes2-phenyl-C≡C)2-2,2'-bpy (BB-bpy), 4-(p-BMes2-phenyl-C≡C)-4'-(p-NPh2-phenyl-C≡C)-2,2'-bpy (BN-bpy), and 4,4'-(p- NPh2-phenyl-C≡C)2-2,2'-bpy (NN-bpy)-along with their heteroleptic copper(I) complexes Cu(L)(PPh3)2(BF4) (L = BB-bpy, BN-bpy, and NN-bpy, respectively). The electron-donor and -acceptor units are connected to the bipyridine core via acetylene linkers. The incorporation of acetylene linkers decreases the dihedral angle between the bridging phenyl and pyridine rings, resulting in a nearly coplanar geometry of the ligands. All free ligands display temperature-dependent luminescence changes, which may be explained by the twisted intramolecular charge-transfer mechanism. Binding with Cu(I) results in significantly red-shifted emission maxima for the heteroleptic complexes Cu(NNbpy)(PPh3)2(BF4) [Cu(NNbpy)] and Cu(BNbpy)(PPh3)2(BF4) [Cu(BNbpy)] relative to those of the free ligands. The electronic and photophysical properties of all compounds were investigated by electrochemical, absorption, and emission spectroscopic analyses as well as density functional theory calculations.

Divergent and Multi-Stage Photoisomerization of Four-Coordinated Boron Compounds with a Naphthyl-Pyridyl/Thiazolyl Backbone.

Examination of the photoreactivity of a new class of N,C-chelate organoboron compounds, including a series of unsymmetrically substituted boron molecules, B(naph-pyridyl)(Ar1 )(Ar2 ) and B(naph-thiazolyl)(Ar1 )(Ar2 ), led to the discovery of new and divergent photothermal isomerization phenomena. These include the clean and regioselective photoisomerization by unsymmetrical boron, forming borepin isomers, some of which further isomerize to the corresponding boratanorcaradiene diastereomer pairs as a result of the generation of two chiral centers. Significantly, the boratanorcaradienes involving a 3-thienyl substituent on boron were found to thermally convert to BN-fluoranthene annulated borapentalene via an unprecedented reversible boratacyclopropane-boratacyclopentene rearrangement. Changing the pyridyl donor to a thiazolyl donor on the boron was found to provide the B(naph-thiazolyl)(Mes)2 compounds with a distinct new photoisomerization pathway-instead of borepin, forming new blue fluorescent polycyclic azaborinine species. This work illustrates the richness and complexity of boron photochemistry.

SNHG3 Functions as miRNA Sponge to Promote Breast Cancer Cells Growth Through the Metabolic Reprogramming.

Cancer-associated fibroblasts (CAFs) are important ingredient in tumor microenvironment. The dynamic interplay between CAFs and cancer cells plays essential roles during tumor development and progression. However, the mechanisms of intercellular communication between CAFs and cancer cells remain largely unknown. We characterized exosomes secreted from breast cancer patient-derived CAFs by transmission electron microscopy. The expression of SNHG3, miR-330-5p, and PKM (Pyruvate Kinase M1/M2) was examined by real-time QPCR and immunoblot. The function of SNHG3 on the growth and metabolism of tumor cells was used by CCK8 and mitochondrial oxygen consumption assays. The binding between SNHG3, miR-330-5p, and PKM was examined by dual luciferase reporter assays. Orthotopical xenograft of breast tumor experiments was performed to determine the function of SNHG3 in vivo. We demonstrated that exosomes secreted from CAFs reprogram the metabolic pathways after tumor cells uptake the exosomes. CAF-secreted exosomal lncRNA SNHG3 served as a molecular sponge for miR-330-5p in breast cancer cells. Moreover, PKM could be targeted by miR-330-5p and was controlled by SNHG3 in breast cancer cells. Mechanistically, SNHG3 knockdown in CAF-secreted exosomes suppressed glycolysis metabolism and cell proliferation by the increase of miR-330-5p and decrease of PKM expression in tumor cells. SNHG3 functions as a miR-330-5p sponge to positively regulate PKM expression, inhibit mitochondrial oxidative phosphorylation, increase glycolysis carboxylation, and enhance breast tumor cell proliferation. Overall, SNHG3 could play a major role in the development and progression of breast cancer and support the therapeutic potential of targeting communication between cancer cells and tumor microenvironment.

Engineered IL-7 Receptor Enhances the Therapeutic Effect of AXL-CAR-T Cells on Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a very aggressive malignant type of tumor that currently lacks effective targeted therapies. In hematological malignancies, chimeric antigen receptor T (CAR-T) cells have shown very significant antitumor ability; however, in solid tumors, the efficacy is poor. In order to apply CAR-T cells in the treatment of TNBC, in this study, constitutively activated IL-7 receptor (C7R) that has been reported is used to enhance the antitumor function of constructed CAR-T cells by ourselves. Using in vitro coincubation experiments with target cells and in vivo antitumor experiments in mice, we found that the coexpressed C7R can significantly improve the activation, cell proliferation, and cytotoxicity of CAR-T cells. In addition, the in vivo experiments suggested that the enhanced CAR-T cells displayed significant antitumor activity in a TNBC subcutaneous xenograft model, in which in vivo, the survival time of CAR-T cells was prolonged. Together, these results indicated that CAR-T cells that coexpress C7R may be a novel therapeutic strategy for TNBC.

Endoscopic Surgery Without Decompressive Craniectomy in Large Putaminal Intracerebral Hemorrhage: Assessment of Efficacy and Safety.

BACKGROUND: Decompressive craniectomy (DC) is performed conventionally for large putaminal intracerebral hemorrhage (ICH). However, DC causes local skull defect and leads to post-surgical cranioplasty. The aim of this study is to investigate the effectiveness and safety of an endoscopic procedure to treat large putaminal ICH without DC. METHODS: This retrospective study included 112 large putaminal ICH patients who underwent hematoma evacuations with either an endoscopic procedure (group A) or with DC (group B) between January 2009 and June 2017. The efficacy was evaluated by mean modified Rankin Scale (mRS) three months after surgery. Safety was evaluated by mortality rate and postoperative complications. Univariate and multivariate logistic regression analyses were performed to determine the risk factors for clinical outcomes. RESULTS: The study included 49 patients in group A and 63 in group B. The mRS scores in both groups were similar after 3 months' follow-up (p = 0.709). There was no difference in the mortality rate between the two groups (p = 0.538). The rate of complications was lower in group A than that in group B (p = 0.024). Smaller preoperative midline shift (p = 0.008) and absent intraventricular extension (p = 0.044) have contributed significantly to better outcomes. CONCLUSION: Endoscopic hematoma evacuation without DC is safe and effective for patients with large putaminal ICH and deserves further investigation, preferably in a randomized controlled setting.

Association between ERα gene Pvu II polymorphism and breast cancer susceptibility: A meta-analysis.

BACKGROUND: Estrogen has played an important role in the development of breast cancer. ER-α PvuII gene polymorphism is in close association with the occurrence risk of breast cancer, but no consensus has been achieved currently. METHODS: PubMed, Embase, China National Knowledge Infrastructure (CNKI) database, Wanfang database, and VIP database were retrieved to collect the case-control studies on association between ERα gene Pvu II polymorphism and breast cancer risk published before September 1, 2017. Newcastle-Ottawa Scale (NOS) was used to assess the quality of the literatures, Stata 14.0 software was applied for meta-analysis, and the pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated. The subgroup analysis was performed to assess the confounding factors, followed by assessment of publication bias and sensitivity analysis. RESULTS: A total of 26 studies were enrolled in the analysis based on inclusion criteria, which included 15,360 patients and 26,423 controls. The results demonstrated that ERα gene Pvu II polymorphism was in significant association with the decrease of breast cancer risk in 3 genetic models (C vs T, OR = 0.962, 95% CI = 0.933-0.992, P = .012; CC vs TT, OR = 0.911, 95% CI = 0.856-0.969, P = .003; CC vs TT/CT, OR = 0.923, 95% CI = 0.874-0.975, P = .004). Subgroup analysis was conducted on the basis of ethnicity and source of controls, whose results illustrated that ERα gene Pvu II polymorphism was in significant association with the decrease of breast cancer risk in Asians rather than in Caucasians (CC vs TT, OR = 0.862, 95% CI = 0.750-0.922, P = .038; CC vs TT/CT, OR = 0.851, 95% CI = 0.755-0.959, P = .008). In population-based subgroup rather than in hospital-based subgroup, ERα gene Pvu II polymorphism was in significant association with the decrease of breast cancer risk in the allele model, homozygous model, dominant model, and recessive model (C vs T, OR = 0.943, 95% CI = 0.911-0.977, P = .001; CC vs TT, OR = 0.878, 95% CI = 0.817-0.944, P = .000; CC/CT vs TT, OR = 0.936, 95% CI = 0.881-0.994, P = .031; CC vs TT/CT, OR = 0.902, 95% CI = 0.847-0.960, P = .001). CONCLUSION: ERα gene Pvu II polymorphism exerts an important function in the progression of breast cancer.

Kinetics and isotherms of Neutral Red adsorption on peanut husk.

Adsorption of Neutral Red (NR) onto peanut husk in aqueous solutions was investigated at 295 K. Experiments were carried out as function of pH, adsorbent dosage, contact time, and initial concentration. The equilibrium adsorption data were analyzed by Langmuir, Freundlich, Temkin, Dubinin-Radushkevich, and Toth isotherm models. The results indicated that the Toth and Langmuir models provided the best correlation of the experimental data. The adsorption capacity of peanut husk for the removal of NR was determined with the Langmuir and found to be 37.5 mg/g at 295 K. The adsorption kinetic data were modeled using the pseudo-first order, pseudo-second order, and intra-particle diffusion kinetic equations. It was seen that the pseudo-first order and pseudo-second order kinetic equations could describe the adsorption kinetics. The intraparticle diffusion model was also used to express the adsorption process at the two-step stage. It was implied that peanut husk may be suitable as adsorbent material for adsorption of NR from aqueous solutions.