Signatures of bosonic Landau levels in a finite-momentum superconductor.

Charged particles subjected to magnetic fields form Landau levels (LLs). Originally studied in the context of electrons in metals1, fermionic LLs continue to attract interest as hosts of exotic electronic phenomena2,3. Bosonic LLs are also expected to realize novel quantum phenomena4,5, but, apart from recent advances in synthetic systems6,7, they remain relatively unexplored. Cooper pairs in superconductors-composite bosons formed by electrons-represent a potential condensed-matter platform for bosonic LLs. Under certain conditions, an applied magnetic field is expected to stabilize an unusual superconductor with finite-momentum Cooper pairs8,9 and exert control over bosonic LLs10-13. Here we report thermodynamic signatures, observed by torque magnetometry, of bosonic LL transitions in the layered superconductor Ba6Nb11S28. By applying an in-plane magnetic field, we observe an abrupt, partial suppression of diamagnetism below the upper critical magnetic field, which is suggestive of an emergent phase within the superconducting state. With increasing out-of-plane magnetic field, we observe a series of sharp modulations in the upper critical magnetic field that are indicative of distinct vortex states and with a structure that agrees with predictions for Cooper pair LL transitions in a finite-momentum superconductor10-14. By applying Onsager's quantization rule15, we extract the momentum. Furthermore, study of the fermionic LLs shows evidence for a non-zero Berry phase. This suggests opportunities to study bosonic LLs, topological superconductivity, and their interplay via transport16, scattering17, scanning probe18 and exfoliation techniques19.

CircNRCAM up-regulates NRCAM to promote papillary thyroid carcinoma progression.

PURPOSE: Papillary Thyroid Carcinoma (PTC) is the most prevalent subtype of Thyroid Carcinoma (THCA), a type of malignancy in the endocrine system. According to prior studies, Neural Cell Adhesion Molecule (NRCAM) has been found to be up-regulated in PTC and stimulates the proliferation and migration of PTC cells. However, the specific mechanism of NRCAM in PTC cells is not yet fully understood. Consequently, this study aimed to investigate the underlying mechanism of NRCAM in PTC cells, the findings of which could provide new insights for the development of potential treatment targets for PTC. METHODS AND RESULTS: Bioinformatics tools were utilized and a series of experiments were conducted, including Western blot, colony formation, and dual-luciferase reporter assays. The data collected indicated that NRCAM was overexpressed in THCA tissues and PTC cells. Circular RNA NRCAM (circNRCAM) was found to be highly expressed in PTC cells and to positively regulate NRCAM expression. Through loss-of-function assays, both circNRCAM and NRCAM were shown to promote the proliferation, invasion, and migration of PTC cells. Mechanistically, this study confirmed that precursor microRNA-506 (pre-miR-506) could bind with m6A demethylase AlkB Homolog 5 (ALKBH5), leading to its m6A demethylation. It was also discovered that circNRCAM could competitively bind to ALKBH5, which restrained miR-506-3p expression and promoted NRCAM expression. CONCLUSION: In summary, circNRCAM could up-regulate NRCAM by down-regulating miR-506-3p, thereby enhancing the biological behaviors of PTC cells.

[Congenital spindle cell/sclerosing rhabdomyosarcoma: a clinicopathological analysis].

Objective: To investigate the clinicopathological features, immunophenotype and molecular genetic characteristics of congenital spindle cell/sclerosing rhabdomyosarcoma. Methods: Sixteen cases (including 10 consultation cases) of congenital spindle cell/sclerosing rhabdomyosarcoma diagnosed at the Beijing Children's Hospital, Capital Medical University, Beijing China, from April 2017 to January 2022 were collected. These cases were evaluated for clinical profiles, histomorphological features, immunophenotype and molecular characteristics. Results: Among the 16 patients, 9 were male and 7 were female. Five cases were present during maternal pregnancy and 11 cases were found immediately after birth. The tumors were located in the chest wall, low back, retroperitoneum, extremities or perineum. The tumors consisted of fasciculated spindle-shaped cells with localized mesenchymal sclerosis and vitreous metaplasia. Immunohistochemistry showed that the tumor cells expressed Desmin, Myogenin, MyoD1, SMA, CD56 and ALK to varying degrees, but not other markers such as CD34, CD99, pan-TRK, S-100 and BCOR. FISH analyses with NCOA2 (8q13) and VGLL2 (6q22) gene breakage probes revealed a breakage translocation in chromosome NCOA2 (8q13) in 4 cases (4/11). In the 6 cases subject to sequencing, a mutation at the p.L122R locus of MYOD1 gene was detected in 1 case (1/6). Two cases were examined by electron microscopy, which showed bundle-arranged myofilaments with some primitive myofilament formation. Five cases were resected with simple surgery, 2 cases were biopsied and followed up with observation only, and 9 cases were treated with surgery and adjuvant chemotherapy. Follow-up was available in 12 cases. At the end of the follow-up, 2 of the 12 patients developed local recurrences and 2 patients survived with disease. Conclusions: Congenital spindle cell/sclerosing rhabdomyosarcoma is a rare subtype of congenital rhabdomyosarcoma. It more commonly occurs in the chest, back and lower limbs of infants than other sites. NCOA2/VGLL2 gene fusion seems to be the most common genetic change. Its prognosis is better than other subtypes of rhabdomyosarcoma and those in adolescents and adults with the same subtype. Analysis and summary of its clinicopathological features can help differentiate it from other soft tissue tumors in infants and children and provide the information for appropriate treatments.

Clinical Recommendations for the use of Neurotropic B vitamins (B1, B6, and B12) for the Management of Peripheral Neuropathy: Consensus from a Multidisciplinary Expert Panel.

INTRODUCTION: Peripheral neuropathy (PN) is an insidious disease that is often asymptomatic during the early stages but which can have a significant impact on quality of life at later stages when nerve damage occurs. There is currently no guidance on the use of neurotropic B vitamins (B1, B6, and B12) for the management of asymptomatic and symptomatic PN. OBJECTIVE: To provide guidance to primary care physicians on an integrated approach to managing PN with neurotropic B vitamins (B1, B6, and B12). MATERIALS AND METHODS: A multidisciplinary panel of eight experts participated in an iterative quasi-anonymous Delphi survey consisting of two rounds of questions and a virtual meeting. A literature review formed the basis of the survey questions. The first round included multiple select, qualitative, and Likert Scale questions; the subsequent round consisted of 2-point scale (agree or disagree) questions that sought to develop consensus-based statements refined from the first round and recommendations derived from discussions during the virtual expert panel meeting. RESULTS: Clinical recommendations for the use of neurotropic B vitamins (B1, B6, and B12) have been developed for the prevention of PN progression or to delay onset in patients at high risk of developing PN. Recommendations have also been provided for the assessment of PN etiology and considerations for the use of loading dose (high dose) and maintenance dose (lower dose) of these neurotropic B vitamins (B1, B6, and B12). CONCLUSION: These clinical recommendations provide an initial step towards formulating comprehensive guidelines for the early and long-term management of PN with neurotropic B vitamins (B1, B6, and B12) and move beyond addressing only neuropathic pain associated with the late stages of PN.

[Myocardial protection of del Nido cardioplegia in adult cardiac and major vascular surgery with long aortic cross-clamp time].

Objective: To explore the safety and myocardial protection efficacy of del Nido cardioplegia in adult cardiac and major vascular surgery with long aortic cross-clamp (ACC) time. Methods: A total of 2 536 patients who underwent adult cardiac and major vascular surgery with ACC time>90 min at Beijing Anzhen Hospital from March 2018 to March 2023 were collected. The patients were divided into two groups according to the type of cardioplegia solution: the del Nido cardioplegia solution group (DC group) and the cold blood cardioplegia solution group (BC group). Preoperative baseline data of the patients (age, gender, comorbidities, ejection fraction, etc) were adjusted using propensity score matching (PSM). Cardiopulmonary bypass (CPB) time, ACC time, total amount of cardioplegia solution, in-hospital mortality rate, length of intensive care unit (ICU) stay, mechanical ventilation time, postoperative complications, left ventricular ejection fraction, and troponin levels were compared between the two groups. Results: After PSM, a total of 306 patients were included, including 223 males and 83 females, with a mean age of (52.0±12.3) years. There were 153 cases in the DC group and 153 cases in the BC group. Compared with the DC group, the cross-clamp time was longer [109(100, 150) min vs 102(91, 133) min, P<0.001], the rate of return to spontaneous rhythm was lower [51.6% (79/153) vs 86.9%(133/153), P<0.001], and intraoperative peak glucose was higher [12.6 (6.5, 15.9) mmol/L vs 10.1 (8.5, 12.4) mmol/L, P=0.005] in the BC group. In addition, perioperative mortality [4.6% (7/153) vs 3.3% (5/153), P=0.132], stroke[3.9% (6/153) vs 3.3% (5/153), P=0.759], renal insufficiency [3.3% (5/153) vs 6.5% (10/153), P=0.186], atrial fibrillation [4.6% (7/153) vs 2.6% (4/153), P=0.652] and low cardiac output syndrome [3.9% (6/153) vs 4.6% (7/153), P=0.716] did not differ between the two groups. Compared with BC group, DC group had lower level of high sensitivity troponin (hsTnI) [1.2 (0.8, 1.8) µg/L vs 1.3 (0.9, 2.3) µg/L, P=0.030] and creatine kinase isoenzyme (CK-MB) [31.0 (20.0, 48.9) µg/L vs 37.0 (24.0, 58.9) µg/L, P=0.011] at 24 h postoperatively, and shorter length of ICU stay [35.6 (19.8, 60.5) h vs 42.6 (21.9, 83.6) h, P=0.015] and mechanical ventilation time [20.5 (15.5, 41.0) h vs 31.5 (17.1, 56.0) h, P=0.012]. Subgroup analysis showed that in the 120-180 minute subgroup, patients in the DC group had a shorter cross-clamp time [132 (124, 135) min vs 136 (124, 138) min, P<0.001], while levels of hsTnI [1.6 (1.1, 2.0) µg/L vs 1.4 (1.0, 2.6) µg/L, P=0.030] and CK-MB [38.8 (23.5, 55.5) µg/L vs 37.0 (24.5, 62.3) µg/L, P=0.011] were higher than those in the BC group. Conclusions: In adult cardiac and major vascular surgery with ACC times>90 min, comparable myocardial protection is observed with the use of DC compared with BC. Additional advantages in glycemic control, return to spontaneous rhythm, and improved surgical procedures make DN an attractive alternative for myocardial protection in adult cardiac surgery.

[Correlation between balloon volume and Meckel's cave size and its influence of percutaneous microballoon compression for trigeminal neuralgia].

Objective: To investigate the correlation between balloon volume and Meckel's cave size during percutaneous puncture microballoon compression (PMC) for trigeminal neuralgia and the influence of the compression coefficient (the ratio of balloon volume/Meckel's cave size) on the prognosis. Methods: Seventy-two patients (28 males and 44 females) aged (62±11) years who underwent PMC under general anesthesia for trigeminal neuralgia in the First Affiliated Hospital of Zhengzhou University from February 2018 to October 2020 were retrospectively collected. All patients underwent preoperative cranial magnetic resonance imaging (MRI) to measure Meckel's cave size, intraoperative balloon volume was recorded, and the compression coefficient was calculated. Follow-up visits were performed preoperatively (T0) and 1 d (T1), 1 month (T2), 3 months (T3), and 6 months (T4) postoperatively, either in the outpatient clinic or by telephone, and the Barrow Neurological Institute pain scale (BNI-P) score, the Barrow Neurological Institute facial numbness (BNI-N) score and the occurrence of complications were recorded and compared at each time point. Patients were divided into 3 groups according to different prognoses: patients in group A (n=48) were with no recurrence of pain and mild facial numbness, patients in group B (n=19) were with no recurrence of pain but severe facial numbness, while those in group C (n=5) had recurrence of pain. The differences in balloon volume, Meckel's cave size, and compression coefficient were compared among the three groups, and the correlation between balloon volume and Meckel's cave size in each group was analyzed by Pearson correlation. Results: The effective rate of PMC for trigeminal neuralgia was 93.1% (67/72). At time points from T0 to T4, patients had BNI-P scores [M (Q1, Q3)] of 4.5 (4.0, 5.0), 1.0 (1.0, 1.0), 1.0 (1.0, 1.0), 1.0 (1.0, 1.0) and 1.0 (1.0, 1.0), and BNI-N scores [M (Q1, Q3)] of 1.0 (1.0, 1.0), 4.0 (3.0, 4.0), 3.0 (3.0, 4.0), 3.0 (2.0, 4.0) and 2.0 (2.0, 3.0), respectively. Compared with those at T0, patients had lower BNI-P scores and higher BNI-N scores from T1 to T4 (all P<0.05). In all patients, group A, group B, and group C, the balloon volume was (0.65±0.15), (0.67±0.15), (0.59±0.15) and (0.67±0.17) cm3, respectively, with no statistically significant difference (P>0.05), while the Meckel's cave size was (0.42±0.12), (0.44±0.11), (0.32±0.07), and (0.57±0.11) cm3, with a statistically significant difference (P<0.001). The balloon volumes and Meckel's cave sizes were all linearly and positively correlated (r=0.852, 0.924, 0.937 and 0.969, all P<0.05). The compression coefficient in group A, B and C was (1.54±0.14), (1.84±0.18) and (1.18±0.10), respectively, with a statistically significant difference (P<0.001). There were no serious intraoperative complications such as death, diplopia, arteriovenous fistula, cerebrospinal fluid leak, and subarachnoid hemorrhage. Conclusions: Intraoperative balloon volume during PMC for trigeminal neuralgia is linearly and positively correlated with the volume of the patient's Meckel's cave. The compression coefficient varies among patients with different prognoses and the compression coefficient may be a factor affecting the patient's prognosis.

[Protective effect of anti-idiopathic pulmonary fibrosis drug Pirfenidone and Sufenidone (SC1011) on pulmonary injury induced by tuberculosis in a mouse tuberculosis model].

Objective: To evaluate the protective effect of anti-idiopathic pulmonary fibrosis (IPF) marketed drug Pirfenidone and its clinical drug Sufenidone (SC1011) against lung injury in a mouse tuberculosis model. Methods: C57BL/6 mouse model of tuberculosis was established. A total of 75 C57BL/6 mice were infected with 1×107 CFU/ml H37Rv suspension by aerosol and randomly divided into untreated (n=9) group, isoniazid+rifampicin+pyrazinamide (HRZ) group (n=22), PFD+HRZ group (n=22), and SC1011+HRZ group (n=22). C57BL/6 mice were infected with H37Rv by aerosol for 6 weeks and then treated. Seven mice in each treatment group were weighed, sacrificed, dissected and observed for lung and spleen lesions at 4 and 8 weeks of treatment. HE staining and Masson staining were used to assess degree of lung injury and fibrosis, respectively. ELISA was used to assess the IFN-γ/TNF-α content in the serum of mice in each treatment group after 4 weeks of treatment. Hydroxyproline (HYP) content in lung tissue was measured by alkaline hydrolysis; meanwhile, CFU counts were used to assess the bacterial load in the lung and spleen of mice in each treatment group and the recurrence of spleen and lung tissue after 12 weeks of drug withdrawal. Results: At 8 weeks, the HYP content in the lung tissue was (630±58), (635±17), and (840±70) µg/mg in the PFD+HRZ, SC1011+HRZ, and HRZ treatment group, respectively (P<0.05).At 8 weeks, the proportion of Masson staining blue-stained area, that was, positive area, in lung tissue was 16.65%±1.82%, 10.01%±2.16%, and 21.36%±3.21%, respectively (F=27.11, P<0.001).The lung injury scores by HE staining at 8 weeks were (5.00±0.50), (5.00±0.47), and (6.89±0.99) points, respectively (F=19.81, P<0.001).The results of 4-week ELISA showed that the levels of TNF-α and IFN-γ in the serum of the SC1011+HRZ-treated group were lower than those of the HRZ-treated group (all P<0.05).The degree of lung injury and fibrosis in PFD+HRZ and SC1011+HRZ treatment groups were lower than those in HRZ treatment group (all P<0.001). The number of viable bacteria in the lung tissue of mice treated with PFD+HRZ, SC1011+HRZ, and HRZ for 4 weeks was lower than that of mice untreated [(1.82±0.10), (1.91±0.05), (1.79±0.17) vs. (5.27±0.07) lg(CFU+1)/ml, all P<0.05)]. And the aseptic transformation of the spleen of mice was achieved in each treatment group at 8 weeks of administration. After 12 weeks of drug withdrawal, the recurrence of lung infection in the SC1011+HRZ treatment group was 3/7 lower than 5/7 in the HRZ treatment group (P>0.05); the recurrence of spleen infection in the SC1011+HRZ treatment group was 1/7 lower than 5/7 in the HRZ treatment group (P>0.05).Pulmonary infection recurred more frequently in PFD+HRZ 6/7 versus HRZ 5/7 (P>0.05). Conclusions: PFD/SC1011, when combined with HRZ, reduced lung injury and reduced secondary fibrosis in pulmonary tuberculosis in C57BL/6 mice. SC1011 combined with HRZ has no significant short-term therapeutic effect on MTB, but may reduce its recurrence rate in long-term treatment, especially in reducing the recurrence rate of mouse spleen.

Health equality, race and pharmacogenomics.

Pharmacogenomics is increasingly moving into mainstream clinical practice. Careful consideration must be paid to inclusion of diverse populations in research, translation and implementation, in the historical and social context of population stratification, to ensure that this leads to improvements in healthcare for all rather than increased health disparities. This review takes a broad and critical approach to the current role of diversity in pharmacogenomics and addresses potential pitfalls in order to raise awareness for prescribers. It also emphasizes evidence gaps and suggests approaches that may minimize negative consequences and promote health equality.

Surgeon specialty effect on early outcomes of elective posterior spinal fusion for adolescent idiopathic scoliosis: a propensity-matched analysis of 965 patients.

BACKGROUND AND OBJECTIVE: Comparative effectiveness research plays a vital role in health care delivery. Specialty training is one of these variables; surgeons who are trained in different specialties may have different outcomes performing the same procedure. The objective of this study was to investigate the impact of spine surgeon specialty (neurosurgery vs orthopedic surgery) on early perioperative outcome measures of elective posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). METHODS: This is a retrospective, 1:4 propensity score-matched cohort study. 5520 AIS patients were reviewed from ACS-NSQIP pediatric database. Propensity score matching was utilized. RESULTS: Patients operated on by orthopedic surgeons were more likely to have shorter operation time (263 min vs 285 min), shorter total hospital stay (95 h vs 118 h), lower rate of return to operating room within the same admission (1.2% vs 3.8%), lower discharge rates after postoperative day 4 (23.8% vs 30.9%), and lower unplanned readmission rate (1.6% vs 4.1%), (p < 0.05). On the other hand, patients operated on by neurosurgeons had lower perioperative blood transfusion rate (62.1% vs 69.8%), (p < 0.05). Other outcome measures and mortality rates were not significantly different between the two cohorts. CONCLUSIONS: This retrospective study found significant differences in early perioperative outcomes of patients undergoing PSF for AIS by neurosurgeons and orthopedic surgeons. Further studies are recommended to corroborate this finding which may trigger changes in the educational curriculum for neurosurgery residents.

Characteristics of two terbutylazine-degrading bacteria and the construction of a live bacterial agent for effective degradation of terbutylazine in soil.

Two kinds of bacteria, named TDJ-7 and TDJ-9, were isolated from the soil, which could degrade terbutylazine effectively. TDJ-7 and TDJ-9 were identified as Bacillus pumilus and Bacillus subtilis. The degradation efficiency of 10mg/L of terbutylazine by TDJ-7 could reach 95% within 6 days, and the strain TDJ-9 could reach 98% under the same conditions. Both strain TDJ-7 and strain TDJ-7 could also effectively degrade simazine, metribuzin, atrazine and ametryn. In addition, strain TDJ-7 and TDJ-9 had been successfully developed into a live bacterial agent that could be used to degrade terbutylazine residue. These results suggest that strain TDJ-7 and TDJ-9 can be used for the bioremediation of terbutylazine or other s-triazine herbicides contamination.

Vulnerable migrants' access to healthcare in the early stages of the COVID-19 pandemic in the UK.

OBJECTIVES: To understand the living conditions, changes in the service user profile, and needs of vulnerable migrants trying to access healthcare in the early stages of the COVID-19 pandemic. STUDY DESIGN: Mixed methods study; using quantitative questionnaire data collected from migrant service users of Doctors of the World UK (DOTW UK) with qualitative data from free-text notes. METHODS: DOTW UK provides drop-in clinics to vulnerable migrants. Consultations switched to remote during the UK's first lockdown. We compared patient profile, well-being, healthcare access and reason for consultations of individuals attending the virtual clinic between March and September 2020 to those of the prepandemic periods between 2011 and 2018. RESULTS: During the pandemic, consultations dropped to under half of the prepandemic numbers, with the shift to remote consultations attracting more users outside of London. DOTW UK's user base changed to include a greater proportion of asylum seekers, younger adults (18-34) and individuals reporting good health. Socio-economic conditions and housing stability deteriorated for the majority of users. Those in the greatest need of healthcare appeared to be less able to access remote services. General practitioner (GP) registration remained the most common reason for contacting the virtual clinic with a lack of knowledge of the healthcare system being the main barrier to access. CONCLUSION: The shift to virtual consultations may have exacerbated existing inequalities in healthcare access for vulnerable migrants. Given that many clinical services continue to operate remotely, it is important to consider the impact such actions have on vulnerable migrants and find ways to support access.

[Attention should be paid to accurate pathological diagnosis of breast cancer].

Breast cancer has replaced lung cancer as the most common malignant tumor in the world. Precise surgical, internal medicine, targeted, radiotherapy, immunotherapy and other treatment methods will improve the survival and quality of life of patients. Accurate pathological diagnosis is the prerequisite and key to achieve clinical accurate treatment. This article makes a review of the relevant content of different submitted specimens and precise pathological diagnosis of breast cancer.

[Altered dynamics of brain spontaneous activity in betel quid dependence chewers].

Objective: To investigate the dynamic characteristics of brain spontaneous activity in betel quid dependence (BQD) chewers and its relationship with clinical indexes. Method: This study was conducted in Hainan General Hospital from April to December 2019 and the data of 53 BQD chewers (37 males and 16 females, aged 20 to 58(38±11) years) and 37 healthy controls (HC) (24 males and 13 females, aged 23-57(42±12) years) were collected. All these subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scan. The dynamic characteristics of resting fMRI indexes, including dynamic amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo) and degree centrality (DC) of these subjects were calculated using the sliding time window method, parameters such as age and dynamic local consistency were analyzed and compared between the two groups. Pearson correlation was used to analyze the relationship between dynamic indexes, betel quid dependence score (BQDS) and disease duration in BQD group. Results: BQD chewers showed decreased dynamic ALFF in the left orbital prefrontal cortex (0.138±0.041 vs 0.171±0.070), the right temporal pole superior temporal gyrus (0.277±0.070 vs 0.319±0.086) and the right inferior parietal lobule (0.223±0.052 vs 0.259±0.088) than HC (all P<0.05). For regional homogeneity, BQD chewers showed a decrease dynamic ReHo in the right inferior temporal gyrus (0.055±0.008 vs 0.061±0.009), the orbital prefrontal cortex (0.058±0.005 vs 0.063±0.008), the right inferior frontal gyrus (0.081±0.006 vs 0.087±0.011), the right superior occipital gyrus (0.056±0.007 vs 0.062±0.008), the left precentral gyrus (0.068±0.008 vs 0.074±0.008), and the left superior frontal gyrus (0.058±0.008 vs 0.064±0.009) than HC (all P<0.05). BQD chewers showed an increase dynamic ReHo in the right precuneus (0.095±0.009 vs 0.089±0.008) (P<0.05). There was no significant difference in DC between the two groups (all P>0.05). The relationships between three dynamic ALFF and BQDS (r=-0.104, -0.015, -0.119), seven dynamic ReHo and BQDS (r=-0.099, -0.141, -0.055, -0.078, -0.027, -0.111, -0.090), three dynamic ALFF and disease duration (r=-0.122, -0.095, -0.171), and seven dynamic ReHo and disease duration (r=0.242, -0.252, 0.035, 0.056, 0.047, 0.081, 0.169) were not statistically significant (all P>0.05). Conclusions: BQD chewers showed a decrease dynamic ReHo and/or ALFF in multiple brain regions dominated by prefrontal cortex, and an increase dynamic ReHo in the right precuneus.

[Investigate developmental coordination disorder of kindergarten children in Zhejiang Province].

In order to investigate developmental coordination disorder (DCD) of kindergarten children in Zhejiang province, 200 ordinary kindergartens were randomly selected by stratified random sampling in 11 prefecture-level cities of Zhejiang Province, and 38 900 children from 1 000 classes in each grade were then randomly selected into the study from June 2019 to December 2019. The Little DCD Questionnaire and a self-designed questionnaire were used to screen the DCD of those children. There were 36 807 valid questionnaires, and 6.50% (2 391/36 807) of them were positive results. The results showed that boy, age ≤5 years, overweight or obesity, left handedness, comorbidity with motor or developmental disorders and premature infants were risk factors of DCD in children. As for parents and families, maternal gestational age<20 years, maternal overweight or obesity before pregnancy, low-middle level education of parents, direct family and low income of family were also associated with DCD in children. Therefore, it is necessary to conduct early prevention and intervention strategies targeting on identified risk factors among relevant population.

[Early onset Epstein-Barr virus-negative diffuse large B cell lymphoma after bilateral lung transplantation: a case report].

Lymphoma after solid organ transplantation is one of the manifestations of post-transplant lymphoproliferative disorders(PTLD). Here we reported a 39-year-old male patient presented with intermittent fever, markedly elevated level of peripheral blood lymphocytes and lactate dehydrogenase(LDH), rapid decrease in hemoglobin and platelet count ten months after bilateral lung transplantation. After systematic evaluation, the patient excluded infectious diseases. Positron emission tomography-computed tomography (PET/CT) revealed diffuse increasing of standard uptake value in bones throughout the body. The bone marrow aspiration, flow cytometric analysis and histopathology confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) with negative Epstein-Barr virus-encoded small RNA (EBER) hybridization in situ. Meanwhile, complicated hemophagocytic lymphohistiocytosis was also diagnosed in the patient based on hypertriglyceridemia, abnormally elevated level of serum ferritin and solvable CD25 (sCD25). Treatment regimen included reduction of immunosuppression, anti-CD20 antibody (CD20+ B cell inhibitor, rituximab) and etoposide. Repeated PET/CT and bone marrow biopsy showed complete remission of lymphoma after 4 months of therapy.

[Study on the pharmacodynamic activity of combinations with the new anti-tuberculosis drug pyrifazimine in vitro and in vivo in mouse].

Objective: To evaluate two-drug combination interaction between pyrifazimine(TBI-166) and anti-drug-resistant tuberculosis group A drugs Bedaquiline (BDQ), Moxifloxacin (MFX) and the new anti-tuberculosis drug Delamanid (DLM), SQ109, Q203, and PBTZ169 in vitro and in vivo in mouse, so as to provide basis for TBI-166 combination therapy. Methods: This study was performed from September 2020 to July 2021. The chessboard method was used to evaluate the interaction between TBI-166 and BDQ, MFX, DLM, SQ109, and PBTZ169. The time-killing kinetics method was used to evaluate the anti-tuberculosis activity of the two-drug combination with partial synergy. The BALB/c mouse acute infection model was used to evaluate the anti-tuberculosis activity at 4 and 8 weeks in the two-drug combination group (TBI-166+BDQ, TBI-166+SQ109, TBI-166+PBTZ169, TBI-166+Q203) and monotherapy groups (TBI-166, BDQ, SQ109, PBTZ169, Q203). Data analysis was performed using an independent sample t-test. Results: After TBI-166 combined with anti-tuberculosis drugs, MIC was reduced to 6.25% to 25.00% of TBI-166 monotherapy. After TBI-166 combined with BDQ, SQ109 and PBTZ169, the partial inhibitory concentration index (FICI) values were 0.53, 0.75 and 0.75, respectively; the time sterilization experiment showed that the viable population of Mycobacterium tuberculosis treated with two-drug combination of TBI-166 and BDQ, SQ109, PBTZ169 for 14 days decreased at least 3 log10 CFU/ml. In the mouse experiments, it was found that, the amount of viable bacteria in lung tissue of BDQ, SQ109 and PBTZ169 combined with TBI-166 groups was lower than that of the monotherapy group,respectively. The lung tissue culture of mice in the TBI-166+BDQ group was negative after 4 weeks of treatment, and the number of live bacteria in the lungs of the TBI-166+BDQ group was 1.49 log10CFU lower than that of the BDQ monotherapy group(P<0.01). Conclusion: In vitro and in vivo experiments in mice revealed that TBI-166 had synergistic anti-tuberculosis activity after being combined with BDQ, SQ109 and PBTZ169, respectively.

[Efficacy and safety of endothelin receptor antagonists combined with phosphodiesterase 5 inhibitor in the treatment of pulmonary arterial hypertension: a network meta-analysis].

Objective: To examine the efficacy and safety of endothelin receptor antagonists (ERA) combined with phosphodiesterase 5 inhibitors (PDE5i) in the treatment of pulmonary artery hypertension (PAH). Methods: Computer-based retrieval was performed on PubMed, Cochrane Library, CNKI, Wanfang, and VIP database (up to February 12th, 2021). Randomized controlled trials about endothelin receptor antagonists (ERAs) or PDE5i in patients with PAH were collected. The change of 6-minute walking distance (6MWD) in 12-16 weeks was used as primary outcome index. Case fatality rate, worsening clinical events, WHO functional class (FC) improvement, adverse events (AEs), serious adverse events (SAE) were the key secondary outcomes indicators. STATA 16.0 software was used for network meta-analysis, and the pooled estimates of odds ratios (ORs) or weighted mean differences (WMDs) and 95% confidence intervals (CIs) of the results were shown. To help explain ORs and WMDs, we used the surface under the cumulative ranking curve (SUCRA) to calculate the probability of each intervention. Results: We included 29 trials with 5 949 participants. In network meta-analysis, Bosentan combined with Sildenafil (WMD=53.93, 95%CI=6.19-101.66) had shown the greatest improvement in 6MWD compared with placebo, followed by Bosentan combined with Tadalafil (WMD=50.84, 95%CI=7.05-94.62), Ambrisentan combined with Tadalafil (WMD=46.67, 95%CI=15.88-77.45), Bosentan (WMD=29.44, 95%CI=5.86-53.02), Ambrisentan (WMD=23.90, 95%CI=0.31-47.48) and Macitentan (WMD=21.57, 95%CI=2.45-40.69). According to SUCRA, the effects of different intervention measures on improving 6MWD in patients with arterial pulmonary hypertension were as follows: Bosentan+Sildenafil (82.9%)>Bosentan+Tadalafil (78.4%)>Ambrisentan+Tadalafil (77.1%)>Bosentan (49.2%)>Sildenafil (48.5%)>Ambrisentan (40.3%)>Macitentan (37.3%)>Tadalafil (33.0%)>Placebo (3.3%). For the WHO functional class, Sildenafil (OR=2.90, 95%CI=1.04-8.08) was optimal compared with placebo, followed by Bosentan (OR=2.15, 95%CI=1.15-4.04), and there was no significant difference in the rest. For clinical worsening, Bosentan combined with Tadalafil (OR=0.08, 95%CI=0.01-0.49) performed best compared with placebo, followed by Bosentan (OR=0.20, 95%CI=0.11-0.38), Bosentan combined with Sildenafil (OR=0.21, 95%CI=0.09-0.46), Ambrisentan combined with Tadalafil (OR=0.27, 95%CI=0.15-0.50), Sildenafil (OR=0.33, 95%CI=0.17-0.66) and Tadalafil (OR=0.44, 95%CI=0.21-0.90). There was no statistical difference between all interventions and placebo in terms of the incidence of adverse events and serious adverse events. For case fatality rate, Ambrisentan (OR=0.28, 95%CI=0.11-0.74) was statistically superior to placebo and there was no statistics difference in the rest. Conclusions: The combination therapy of ERAs and PDE5i performed well in the short-term improvement of motor function. Furthermore, there was no significant difference with monotherapy in terms of safety. However, it is worth emphasizing that the choice of treatment should be based on the patient's individualized situation and the patient's requirements.

LncRNA SNHG14 promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells via regulating miR-185-5p/WISP2 axis.

Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) is vital for bone formation, and its dysfunction is linked to osteoporosis (OP). In this work, we explored the function of long non-coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) in regulating osteogenic differentiation of hBMSCs. In the present study, the expression of SNHG14 in hBMSCs obtained from OP patients was measured by quantitative real-time polymerase chain reaction (qRT-PCR). SNHG14 was over-expressed or knocked down in hBMSCs, and the expression levels of OP-related genes (ALP, OCN, and OPN) in hBMSCs were detected by qRT-PCR and Western blot. StarBase database and miRanda database were used to predict the binding sites between SNHG14 and miR-185-5p, and between miR-185-5p and 3'UTR of WNT1 inducible signaling pathway protein 2 (WISP2), respectively. Luciferase reporter gene assay was used to validate the binding relationship between SNHG14 and miR-185-5p, and miR-185-5p and 3'UTR of WISP2, respectively. Here, we report that SNHG14 was significantly down-regulated in hBMSCs obtained from patients with OP. Overexpression of SNHG14 promoted osteogenic differentiation, while knockdown of SNHG14 worked oppositely. Mechanistically, miR-185-5p was demonstrated to be a target of SNHG14, and could reverse the function of SNHG14. Additionally, WISP2 was identified as a target gene of miR-185-5p in hBMSCs and could be indirectly regulated by SNHG14. Taken together, down-regulation of SNHG14 in hBMSCs accelerated the progression of OP via regulating miR-185-5p/WISP2 axis.

Controlled expression of lysis gene E by a mutant of the promoter pL of the thermo-inducible λcI857-pL system.

AIMS: To identify a lambda promoter pL mutant that could extend the thermal stability of the thermo-inducible λcI857-pR/pL system and to evaluate the effects of the modified system for the controlled expression of lysis gene E during the production of bacterial ghosts (BGs). METHODS AND RESULTS: The promoter pL mutant was identified by random mutagenesis and site-directed mutagenesis. The results showed that a T â†’ 35C mutation in the pL promoter was responsible for the phenotype alteration. Under the same induction conditions, the lysis rates of the modified lytic system on Escherichia coli and Salmonella enteritidis were significantly lower than that of the control, while the lysis rates of Escherichia coli with the thermo-inducible lytic system were significantly higher than that of S. enteritidis with the corresponding plasmid (P < 0·05). CONCLUSIONS: Increasing the heat stability of the thermo-inducible lytic systems decreased lysis efficiency during the production of BGs. There exist differences in the lysis efficiency of thermo-inducible lytic systems between different bacterial strains. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings enrich current knowledge about modifications to thermo-inducible systems and provide a reference for the application of these modified systems for the production of BGs and controlled gene expression in bacteria.

Isolation of 2 simazine-degrading bacteria and development of a microbial agent for bioremediation of simazine pollution.

Simazine was one of the most commonly used herbicides and was widely used to control broadleaf weeds in agriculture and forestry. Its widespread use had caused wide public concern for its high ecological toxicity. In order to remove simazine residues, 2 strains capable of effectively degrading simazine were isolated from the soil and named SIMA-N5 and SIMA-N9. SIMA-N5 was identified as Bacillus licheniformis by 16SrRNA sequence analysis, and SIMA-N9 was Bacillus altitudinis. According to the degradation ratio of simazine in a certain period of time, the degradation ability of different strains was evaluated. The degradation efficiency of simazine (5 mg/L) by SIMA-N9 could reach about 98% in 5d, and the strain SIMA-N5 could reach 94% under the same conditions. In addition, the addition of Pennisetum rhizosphere soil during the process of degrading simazine by strain SIMA-N9 could effectively improve the degradation efficiency. The strain SIMA-N9 has been developed as a microbial agent for the bioremediation of simazine contamination in soil. The new microbial agent developed by using SIMA-N9 has achieved satisfactory application effects. Based on the research results already obtained in this study, it was considered that strain SIMA-N9 and its live bacterial agent could play an important role in bioremediation of simazine pollution. This study could not only provide a set of solutions to the simazine pollution, but also provide a reference for the treatment of other pesticide pollution.